{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:16:32Z","timestamp":1789384592982,"version":"build-2803163510"},"reference-count":259,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health Research Program 2018","award":["2635256"],"award-info":[{"award-number":["2635256"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs, antipsychotic, and immunosuppressant drugs are known to induce cardiotoxic and neurotoxic effects. Recent studies have demonstrated that the impairment of the nuclear factor erythroid 2\u2013related factor 2 (Nrf2) pathway is a primary event in the pathophysiology of drug-induced cardiotoxicity and neurotoxicity. The Nrf2 pathway regulates the expression of different genes whose products are involved in antioxidant and inflammatory responses and the detoxification of toxic species. Cardiotoxic drugs, such as the anthracycline doxorubicin, or neurotoxic drugs, such as paclitaxel, suppress or impair the Nrf2 pathway, whereas the rescue of this pathway counteracts both the oxidative stress and inflammation that are related to drug-induced cardiotoxicity and neurotoxicity. Therefore Nrf2 represents a novel pharmacological target to develop new antidotes in the field of clinical toxicology. Interestingly, carnosine (\u03b2-alanyl-l-histidine), an endogenous dipeptide that is characterized by strong antioxidant, anti-inflammatory, and neuroprotective properties is able to rescue\/activate the Nrf2 pathway, as demonstrated by different preclinical studies and preliminary clinical evidence. Starting from these new data, in the present review, we examined the evidence on the therapeutic potential of carnosine as an endogenous antidote that is able to rescue the Nrf2 pathway and then counteract drug-induced cardiotoxicity and neurotoxicity.<\/jats:p>","DOI":"10.3390\/molecules27144452","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T20:52:41Z","timestamp":1657659161000},"page":"4452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1571-5327","authenticated-orcid":false,"given":"Giuseppe","family":"Caruso","sequence":"first","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"},{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Privitera","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-6900","authenticated-orcid":false,"given":"Barbara Moura","family":"Antunes","sequence":"additional","affiliation":[{"name":"Facultad de Deportes, Universidad Aut\u00f3noma de Baja California, Ensenada 22890, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-7279","authenticated-orcid":false,"given":"Giuseppe","family":"Lazzarino","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan Marie","family":"Lunte","sequence":"additional","affiliation":[{"name":"Ralph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047, USA"},{"name":"Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA"},{"name":"Department of Chemistry, University of Kansas, Lawrence, KS 66047, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-6744","authenticated-orcid":false,"given":"Giancarlo","family":"Aldini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Caraci","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"},{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"ref_1","first-page":"S241","article-title":"Antidotes in poisoning","volume":"23","author":"Chacko","year":"2019","journal-title":"Indian J. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100216","DOI":"10.1016\/j.xcrm.2021.100216","article-title":"Toward a broader view of mechanisms of drug cardiotoxicity","volume":"2","author":"Mamoshina","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/bs.pbr.2015.07.004","article-title":"Drug-induced neurotoxicity in addiction medicine: From prevention to harm reduction","volume":"223","author":"Ekhtiari","year":"2016","journal-title":"Prog. Brain Res."},{"key":"ref_4","first-page":"397","article-title":"Drugs and pharmaceuticals: Management of intoxication and antidotes","volume":"100","author":"Smith","year":"2010","journal-title":"Mol. Clin. Environ. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"705","DOI":"10.3109\/15563659509010633","article-title":"The relative efficacy of antidotes","volume":"33","author":"Jacobsen","year":"1995","journal-title":"J. Toxicol. Clin. Toxicol."},{"key":"ref_6","first-page":"153","article-title":"Principles of toxicotherapy: General and specific therapy","volume":"4","author":"Karami","year":"2015","journal-title":"Sch. Acad. J. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhang, M.Y., Dugbartey, G.J., Juriasingani, S., and Sener, A. (2021). Hydrogen sulfide metabolite, sodium thiosulfate: Clinical applications and underlying molecular mechanisms. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126452"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1021\/acschemneuro.2c00201","article-title":"Neuroprotective effect of carnosine is mediated by insulin-degrading enzyme","volume":"13","author":"Distefano","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Grasso, M., Caruso, G., Godos, J., Bonaccorso, A., Carbone, C., Castellano, S., Currenti, W., Grosso, G., Musumeci, T., and Caraci, F. (2021). Improving cognition with nutraceuticals targeting tgf-\u03b21 signaling. Antioxidants, 10.","DOI":"10.3390\/antiox10071075"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Theofilidis, G., Bogdanis, G.C., Koutedakis, Y., and Karatzaferi, C. (2018). Monitoring exercise-induced muscle fatigue and adaptations: Making sense of popular or emerging indices and biomarkers. Sports, 6.","DOI":"10.3390\/sports6040153"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1152\/physrev.00039.2012","article-title":"Physiology and pathophysiology of carnosine","volume":"93","author":"Boldyrev","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1152\/japplphysiol.00397.2007","article-title":"Beta-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters","volume":"103","author":"Derave","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12970-015-0090-y","article-title":"International society of sports nutrition position stand: Beta-alanine","volume":"12","author":"Trexler","year":"2015","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.2174\/1381612825666191209115431","article-title":"\u0392-amyloid and oxidative stress: Perspectives in drug development","volume":"25","author":"Caruso","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7003","DOI":"10.1007\/s00216-015-8865-1","article-title":"Indirect detection of superoxide in raw 264.7 macrophage cells using microchip electrophoresis coupled to laser-induced fluorescence","volume":"407","author":"Siegel","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Caruso, G., Godos, J., Privitera, A., Lanza, G., Castellano, S., Chillemi, A., Bruni, O., Ferri, R., Caraci, F., and Grosso, G. (2022). Phenolic acids and prevention of cognitive decline: Polyphenols with a neuroprotective role in cognitive disorders and alzheimer\u2019s disease. Nutrients, 14.","DOI":"10.3390\/nu14040819"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1759091419899782","DOI":"10.1177\/1759091419899782","article-title":"Nrf2 as a therapeutic target in neurodegenerative diseases","volume":"12","author":"Brandes","year":"2020","journal-title":"ASN Neuro"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"H1453","DOI":"10.1152\/ajpheart.00554.2015","article-title":"Drug-induced mitochondrial dysfunction and cardiotoxicity","volume":"309","author":"Varga","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s40272-014-0085-1","article-title":"Managing chemotherapy-related cardiotoxicity in survivors of childhood cancers","volume":"16","author":"Lipshultz","year":"2014","journal-title":"Pediatric Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"348","DOI":"10.21037\/atm.2017.06.35","article-title":"Cardiotoxicity of cancer chemotherapy: Identification, prevention and treatment","volume":"5","author":"Jain","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.recesp.2016.12.032","article-title":"Early diagnosis and prediction of anticancer drug-induced cardiotoxicity: From cardiac imaging to \u201comics\u201d technologies","volume":"70","author":"Madonna","year":"2017","journal-title":"Rev. Espa\u00f1ola Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1007\/s00246-015-1176-7","article-title":"Current views on anthracycline cardiotoxicity in childhood cancer survivors","volume":"36","author":"Sadurska","year":"2015","journal-title":"Pediatric Cardiol."},{"key":"ref_23","first-page":"16","article-title":"Clinical updates on drug-induced cardiotoxicity","volume":"9","author":"Iqubal","year":"2018","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1177\/009286150103500134","article-title":"Evaluation of the characteristics of safety withdrawal of prescription drugs from worldwide pharmaceutical markets-1960 to 1999","volume":"35","author":"Fung","year":"2001","journal-title":"Drug Inf. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s10557-016-6711-0","article-title":"Anthracycline chemotherapy and cardiotoxicity","volume":"31","author":"McGowan","year":"2017","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s11920-016-0704-3","article-title":"Systematic review of clozapine cardiotoxicity","volume":"18","author":"Curto","year":"2016","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_27","first-page":"243","article-title":"Cardiologic side effects of psychotropic drugs","volume":"8","author":"Marano","year":"2011","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.schres.2018.02.058","article-title":"Potentially fatal outcomes associated with clozapine","volume":"199","author":"Li","year":"2018","journal-title":"Schizophr. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cnc.2015.07.002","article-title":"Mechanisms of cardiotoxicity and the development of heart failure","volume":"27","author":"Lee","year":"2015","journal-title":"Crit. Care Nurs. Clin. N. Am."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Klimas, J. (2012). Drug-Induced Cardiomyopathies, Intech Open Access Publisher.","DOI":"10.5772\/29349"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1046\/j.1365-2125.2000.00230.x","article-title":"Cyp2d6 and cyp2c19 genotypes of patients with terodiline cardiotoxicity identified through the yellow card system","volume":"50","author":"Ford","year":"2000","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1161\/CIRCULATIONAHA.118.037934","article-title":"Genetic variants associated with cancer therapy-induced cardiomyopathy","volume":"140","author":"Kim","year":"2019","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1200\/JCO.2002.20.6.1491","article-title":"Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer","volume":"20","author":"Sloan","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/PRA.0000000000000151","article-title":"The use of fluoxetine in a patient with takotsubo cardiomyopathy","volume":"22","author":"Conrad","year":"2016","journal-title":"J. Psychiatr Pract"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2165\/00139709-200524030-00013","article-title":"Tricyclic antidepressant poisoning: Cardiovascular toxicity","volume":"24","author":"Thanacoody","year":"2005","journal-title":"Toxicol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.2174\/1381612043383872","article-title":"Cardiovascular side effects of new antidepressants and antipsychotics: New drugs, old concerns?","volume":"10","author":"Pacher","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/bjaceaccp\/mku027","article-title":"Local anaesthetic systemic toxicity","volume":"15","author":"Christie","year":"2015","journal-title":"BJA Educ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1161\/CIRCULATIONAHA.110.940569","article-title":"Cardiovascular effects of cocaine","volume":"122","author":"Schwartz","year":"2010","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2174\/1568026013395164","article-title":"The cardiotoxicity of local anesthetics: The place of ropivacaine","volume":"1","author":"Graf","year":"2001","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"95","DOI":"10.4103\/0019-5049.93362","article-title":"Lidocaine not so innocent: Cardiotoxicity after topical anaesthesia for bronchoscopy","volume":"56","author":"Vymazal","year":"2012","journal-title":"Indian J. Anaesth."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.psym.2012.11.001","article-title":"Qtc prolongation, torsades de pointes, and psychotropic medications","volume":"54","author":"Beach","year":"2013","journal-title":"Psychosomatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1385\/COMP:32:2:94","article-title":"Pergolide-associated valvular heart disease","volume":"32","author":"Waller","year":"2006","journal-title":"Compr. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/S1474-4422(07)70218-1","article-title":"Fibrotic heart-valve reactions to dopamine-agonist treatment in parkinson\u2019s disease","volume":"6","author":"Antonini","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"438403","DOI":"10.1155\/2015\/438403","article-title":"5-ht2b receptor antagonists inhibit fibrosis and protect from rv heart failure","volume":"2015","author":"Janssen","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.acvd.2013.02.003","article-title":"Drug-induced valvular heart disease: An update","volume":"106","author":"Andrejak","year":"2013","journal-title":"Arch. Cardiovasc. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1016\/j.hrthm.2011.07.015","article-title":"Propoxyphene-induced torsades de pointes","volume":"8","author":"Adler","year":"2011","journal-title":"Heart Rhythm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fcvm.2020.00026","article-title":"Cardiotoxicity of Anthracyclines","volume":"7","author":"Cardinale","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/bcp.13008","article-title":"Recommendations for genetic testing to reduce the incidence of anthracycline-induced cardiotoxicity","volume":"82","author":"Aminkeng","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"795602","DOI":"10.1155\/2015\/795602","article-title":"Chemotherapy-induced cardiotoxicity: Overview of the roles of oxidative stress","volume":"2015","author":"Angsutararux","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.2459\/JCM.0000000000000379","article-title":"Role of biomarkers in monitoring antiblastic cardiotoxicity","volume":"17","author":"Novo","year":"2016","journal-title":"J. Cardiovasc. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fphys.2018.00167","article-title":"Antineoplastic drug-induced cardiotoxicity: A redox perspective","volume":"9","author":"Varricchi","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/j.1365-2141.2008.06997.x","article-title":"Bortezomib, doxorubicin and dexamethasone (pad) front-line treatment of multiple myeloma: Updated results after long-term follow-up","volume":"141","author":"Popat","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI72931","article-title":"Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation","volume":"124","author":"Ichikawa","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1093\/eurheartj\/ehv305","article-title":"Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications","volume":"36","author":"Gori","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S1734-1140(09)70018-0","article-title":"Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron","volume":"61","author":"Hrdina","year":"2009","journal-title":"Pharmacol. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1586\/1744666X.2014.962996","article-title":"Methotrexate: An old new drug in autoimmune disease","volume":"10","author":"Cipriani","year":"2014","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_57","first-page":"8641026","article-title":"Paeonol attenuates methotrexate-induced cardiac toxicity in rats by inhibiting oxidative stress and suppressing tlr4-induced nf-\u03bab inflammatory pathway","volume":"2020","author":"Morsy","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_58","first-page":"1024","article-title":"Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases","volume":"17","author":"Donisan","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1182\/blood.V68.5.1114.1114","article-title":"Cyclophosphamide cardiotoxicity: An analysis of dosing as a risk factor","volume":"68","author":"Goldberg","year":"1986","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ctrv.2015.11.005","article-title":"Low dose cyclophosphamide: Mechanisms of t cell modulation","volume":"42","author":"Madondo","year":"2016","journal-title":"Cancer Treat Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/S0735-1097(99)00006-6","article-title":"Drug-induced heart failure","volume":"33","author":"Feenstra","year":"1999","journal-title":"J. Am. Coll Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.mito.2004.05.010","article-title":"Cardiomyopathy, nucleoside reverse transcriptase inhibitors and mitochondria are linked through aids and its therapy","volume":"4","author":"Lewis","year":"2004","journal-title":"Mitochondrion"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s10557-021-07181-3","article-title":"The molecular mechanisms of cardiotoxicity induced by her2, vegf, and tyrosine kinase inhibitors: An updated review","volume":"36","author":"Wu","year":"2021","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"675","DOI":"10.3892\/mco.2016.800","article-title":"Cardiotoxicity associated with targeted cancer therapies","volume":"4","author":"Chen","year":"2016","journal-title":"Mol. Clin. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e000073","DOI":"10.1136\/esmoopen-2016-000073","article-title":"Twenty years of anti-her2 therapy-associated cardiotoxicity","volume":"1","author":"Lambertini","year":"2016","journal-title":"ESMO Open"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.1111\/bph.13213","article-title":"Effects of acute and chronic sunitinib treatment on cardiac function and calcium\/calmodulin-dependent protein kinase ii","volume":"172","author":"Mooney","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.taap.2015.03.008","article-title":"Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types","volume":"285","author":"Doherty","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_68","first-page":"70","article-title":"Trastuzumab-induced cardiac dysfunction: A \u2018dual-hit\u2019","volume":"16","author":"Zeglinski","year":"2011","journal-title":"Exp. Clin. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2147\/CMAR.S77400","article-title":"Cancer therapy and cardiovascular risk: Focus on bevacizumab","volume":"7","author":"Economopoulou","year":"2015","journal-title":"Cancer Manag. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ntt.2014.04.041","article-title":"Behavioral pharmacology of cocaine and amphetamine in rats perinatally exposed to polychlorinated biphenyls (pcbs)","volume":"43","author":"Sable","year":"2014","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"A1654","DOI":"10.1097\/01.ccm.0000458726.25787.e9","article-title":"1259: Cocaine induced cardiotoxicity","volume":"42","author":"Pallavi","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s10741-014-9418-y","article-title":"Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity","volume":"19","author":"Liaudet","year":"2014","journal-title":"Heart Fail. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/clc.20746","article-title":"Cocaine and the heart","volume":"33","author":"Maraj","year":"2010","journal-title":"Clin. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/cphy.c140046","article-title":"Alcohol effects on cardiac function","volume":"5","author":"Gardner","year":"2015","journal-title":"Compr. Physiol."},{"key":"ref_75","unstructured":"Gardenhire, D.S. (2015). Drugs affecting the central nervous system. Rau\u2019s Respiratory Care Pharmacology, Elsevier."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nrcardio.2015.91","article-title":"Cardiovascular risks and benefits of moderate and heavy alcohol consumption","volume":"12","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"28982","DOI":"10.3402\/jchimp.v5.28982","article-title":"Partially reversible bortezomib-induced cardiotoxicity: An unusual cause of acute cardiomyopathy","volume":"5","author":"Meseeha","year":"2015","journal-title":"J. Community Hosp. Intern. Med. Perspect."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Xiao, Y., Yin, J., Wei, J., and Shang, Z. (2014). Incidence and risk of cardiotoxicity associated with bortezomib in the treatment of cancer: A systematic review and meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087671"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1056\/NEJMoa1609214","article-title":"Fulminant myocarditis with combination immune checkpoInt. blockade","volume":"375","author":"Johnson","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.2174\/0929867324666170407125017","article-title":"Immune checkpoInt. inhibitors and cardiac toxicity: An emerging issue","volume":"25","author":"Varricchi","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"799","DOI":"10.2217\/imt-2016-0029","article-title":"Immune checkpoInt. inhibitors side effects and management","volume":"8","author":"Kourie","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/1-4020-5688-5_8","article-title":"A biological rationale for the cardiotoxic effects of rofecoxib: Comparative analysis with other cox-2 selective agents and nsaids","volume":"42","author":"Mason","year":"2007","journal-title":"Subcell. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ejvsextra.2008.11.002","article-title":"Cyclo-oxygenase-2 inhibitors and peripheral thrombosis\u2014A case report demonstrating a possible adverse effect","volume":"17","author":"Chandra","year":"2009","journal-title":"EJVES Extra"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1016\/S0960-894X(03)00492-X","article-title":"Prediction of herg potassium channel affinity by traditional and hologrAm. qsar methods","volume":"13","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1164\/rccm.201402-0385CI","article-title":"Macrolide antibiotics and the risk of cardiac arrhythmias","volume":"189","author":"Albert","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_86","first-page":"806","article-title":"Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics","volume":"296","author":"Anderson","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/nrd1201","article-title":"Mitochondrial toxicity of nrti antiviral drugs: An integrated cellular perspective","volume":"2","author":"Lewis","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.redox.2017.06.011","article-title":"Azidothymidine-triphosphate impairs mitochondrial dynamics by disrupting the quality control system","volume":"13","author":"Nomura","year":"2017","journal-title":"Redox Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/jcph.872","article-title":"Electrophysiological adverse effects of direct acting antivirals in patients with chronic hepatitis c","volume":"57","author":"Parrella","year":"2017","journal-title":"J. Clin. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0008-6363(00)00119-X","article-title":"The potential for qt prolongation and pro-arrhythmia by non-anti-arrhythmic drugs: Clinical and regulatory implications. Report on a policy conference of the european society of cardiology","volume":"47","author":"Haverkamp","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1124\/mol.111.075135","article-title":"Molecular determinants of pentamidine-induced herg trafficking inhibition","volume":"81","author":"Dennis","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.vascn.2014.09.005","article-title":"Human stem cell-derived cardiomyocytes detect drug-mediated changes in action potentials and ion currents","volume":"70","author":"Gibson","year":"2014","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1124\/jpet.105.093393","article-title":"Comparative evaluation of herg currents and qt intervals following challenge with suspected torsadogenic and nontorsadogenic drugs","volume":"316","author":"Katchman","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ntt.2008.12.003","article-title":"Relevance of in vitro neurotoxicity testing for regulatory requirements: Challenges to be considered","volume":"32","author":"Hogberg","year":"2010","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.1741-4520.2012.00377.x","article-title":"Developmental neurotoxicity testing: A path forward","volume":"52","author":"Crofton","year":"2012","journal-title":"Congenit. Anom."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.tiv.2015.05.016","article-title":"Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary cns in vitro models","volume":"30","author":"Schultz","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/026119290603400113","article-title":"Metabolism: A bottleneck in in vitro toxicological test development: The report and recommendations of ecvAm. workshop 54","volume":"34","author":"Coecke","year":"2006","journal-title":"Altern. Lab. Anim."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Fresta, C.G., Fidilio, A., Caruso, G., Caraci, F., Giblin, F.J., Leggio, G.M., Salomone, S., Drago, F., and Bucolo, C. (2020). A new human blood-retinal barrier model based on endothelial cells, pericytes, and astrocytes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051636"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1517\/17425255.1.4.701","article-title":"Evaluation of neurotoxic potential by use of in vitro systems","volume":"1","author":"Harry","year":"2005","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.tiv.2008.12.011","article-title":"New strategy for alerting central nervous system toxicity: Integration of blood\u2013brain barrier toxicity and permeability in neurotoxicity assessment","volume":"23","author":"Prieto","year":"2009","journal-title":"Toxicol. In Vitro"},{"key":"ref_101","unstructured":"Brenner, G., and Stevens, C.W. (2010). Antineoplastic Drugs, Text Book of Pharmacology, Saunders Elsevier."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Rang, H., Dale, M., and Ritter, J. (2012). Anticancer Drugs, Text Book of Pharmacology, Elsevier.","DOI":"10.1016\/B978-0-7020-3471-8.00055-X"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2165\/00003495-199957020-00002","article-title":"Clinical and preclinical modulation of chemotherapy-induced toxicity in patients with cancer","volume":"57","author":"Hoekman","year":"1999","journal-title":"Drugs"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5455\/2319-2003.ijbcp000812","article-title":"Toxicities of anticancer drugs and its management","volume":"1","author":"Remesh","year":"2012","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.ejrnm.2015.07.015","article-title":"Child with acute methotrexate related neurotoxicity: Can diffusion weighted mri help?","volume":"46","author":"Youssef","year":"2015","journal-title":"Egypt. J. Radiol. Nucl. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1200\/JCO.2013.53.0808","article-title":"Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia","volume":"32","author":"Bhojwani","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.biopsych.2015.02.008","article-title":"The effect of antipsychotic treatment on cortical gray matter changes in schizophrenia: Does the class matter? A meta-analysis and meta-regression of longitudinal magnetic resonance imaging studies","volume":"78","author":"Vita","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.5604\/17322693.1175009","article-title":"The neurotoxicity of pyridinium metabolites of haloperidol","volume":"69","author":"Sloderbach","year":"2015","journal-title":"Postepy Hig. Med. Dosw."},{"key":"ref_109","first-page":"195","article-title":"Multiple neurotoxic effects of haloperidol resulting in neuronal death","volume":"29","author":"Nasrallah","year":"2017","journal-title":"Ann. Clin. Psychiatry"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Caruso, G., Grasso, M., Fidilio, A., Tascedda, F., Drago, F., and Caraci, F. (2020). Antioxidant properties of second-generation antipsychotics: Focus on microglia. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120457"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/hup.470050323","article-title":"Reported neurotoxicity with the lithium\/haloperidol combination and other neuroleptics\u2014A literature review","volume":"5","author":"Batchelor","year":"1990","journal-title":"Hum. Psychopharmacol. Clin. Exp."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1600-0047.2004.00295.x","article-title":"Novel antipsychotics in bipolar and schizoaffective mania","volume":"109","author":"Mensink","year":"2004","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Hsu, C.W., Lee, Y., Lee, C.Y., and Lin, P.Y. (2016). Neurotoxicity and nephrotoxicity caused by combined use of lithium and risperidone: A case report and literature review. BMC Pharmacol. Toxicol., 17.","DOI":"10.1186\/s40360-016-0101-x"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2147\/OAEM.S241501","article-title":"Cyclosporine-a-based immunosuppressive therapy-induced neurotoxicity: A case report","volume":"12","author":"Teimouri","year":"2020","journal-title":"Open Access Emerg. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1007\/s12098-019-02912-9","article-title":"Cyclosporine in resistant systemic arthritis\u2014A cheaper alternative to biologics","volume":"86","author":"Pal","year":"2019","journal-title":"Indian J. Pediatr."},{"key":"ref_116","first-page":"319","article-title":"Cyclosporine in pediatric nephrology","volume":"12","author":"Soylu","year":"2018","journal-title":"Iran. J. Kidney Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cll.2018.10.008","article-title":"Novel targets of immunosuppression in transplantation","volume":"39","author":"Shin","year":"2019","journal-title":"Clin. Lab. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/bmt.2016.232","article-title":"Long-term outcome following cyclosporine-related neurotoxicity in paediatric allogeneic haematopoietic stem cell transplantation","volume":"52","author":"Straathof","year":"2017","journal-title":"Bone Marrow Transplant."},{"key":"ref_119","first-page":"170","article-title":"Neurotoxicity of immunosuppressive therapies in organ transplantation","volume":"8","author":"Anghel","year":"2013","journal-title":"Maedica"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1034\/j.1600-0609.2001.t01-1-00440.x","article-title":"Clinical findings and magnetic resonance imaging in severe cyclosporine-related neurotoxicity after allogeneic bone marrow transplantation","volume":"67","author":"Trullemans","year":"2001","journal-title":"Eur. J. Haematol."},{"key":"ref_121","first-page":"1","article-title":"Two decades of tacrolimus in renal transplant: Basic science and clinical evidences","volume":"15","author":"Shrestha","year":"2017","journal-title":"Exp. Clin. Transplant."},{"key":"ref_122","first-page":"23","article-title":"Nephro and neurotoxicity of calcineurin inhibitors and mechanisms of rejections: A review on tacrolimus and cyclosporin in organ transplantation","volume":"1","year":"2012","journal-title":"J. Nephropathol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.transproceed.2021.12.036","article-title":"Long-term outcome after tacrolimus-related neurotoxicity in pediatric living donor liver transplantation","volume":"54","author":"Ueno","year":"2022","journal-title":"Transplant. Proc."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"610102","DOI":"10.3389\/fphar.2020.610102","article-title":"Astragaloside iv alleviates tacrolimus-induced chronic nephrotoxicity via p62-keap1-Nrf2 pathway","volume":"11","author":"Gao","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-061516-045037","article-title":"Oxidative stress","volume":"86","author":"Sies","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.2174\/0929867326666190712091515","article-title":"Inflammation as the common biological link between depression and cardiovascular diseases: Can carnosine exert a protective role?","volume":"27","author":"Caruso","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrd1330","article-title":"Neurodegenerative diseases and oxidative stress","volume":"3","author":"Barnham","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrd4002","article-title":"Modulation of oxidative stress as an anticancer strategy","volume":"12","author":"Gorrini","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1152\/physrev.00023.2017","article-title":"The keap1-Nrf2 system: A thiol-based sensor-effector apparatus for maintaining redox homeostasis","volume":"98","author":"Yamamoto","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12964-019-0435-2","article-title":"Dual roles and therapeutic potential of keap1-Nrf2 pathway in pancreatic cancer: A systematic review","volume":"17","author":"Qin","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.pharep.2016.12.011","article-title":"The Nrf2-are signaling pathway: An update on its regulation and possible role in cancer prevention and treatment","volume":"69","author":"Paluszczak","year":"2017","journal-title":"Pharmacol. Rep."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1128\/MCB.01639-08","article-title":"Acetylation of Nrf2 by p300\/cbp augments promoter-specific DNA binding of Nrf2 during the antioxidant response","volume":"29","author":"Sun","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"8984","DOI":"10.1074\/jbc.M709040200","article-title":"Multiple nuclear localization signals function in the nuclear import of the transcription factor Nrf2","volume":"283","author":"Theodore","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"10895","DOI":"10.1128\/MCB.25.24.10895-10906.2005","article-title":"The carboxy-terminal neh3 domain of Nrf2 is required for transcriptional activation","volume":"25","author":"Nioi","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1046\/j.1365-2443.2001.00469.x","article-title":"Two domains of Nrf2 cooperatively bind cbp, a creb binding protein, and synergistically activate transcription","volume":"6","author":"Katoh","year":"2001","journal-title":"Genes Cells"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.1128\/MCB.00180-12","article-title":"Structural and functional characterization of Nrf2 degradation by the glycogen synthase kinase 3\/\u03b2-trcp axis","volume":"32","author":"Rada","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1158\/0008-5472.CAN-12-3386","article-title":"Rxr\u03b1 inhibits the Nrf2-are signaling pathway through a direct interaction with the Neh7 domain of Nrf2","volume":"73","author":"Wang","year":"2013","journal-title":"Cancer Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.1073\/pnas.0914036107","article-title":"Keap1 is a forked-stem dimer structure with two large spheres. enclosing the intervening, double glycine repeat, and c-terminal domains","volume":"107","author":"Ogura","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.tibs.2008.12.008","article-title":"Nrf2 and keap1 mutations: Permanent activation of an adaptive response in cancer","volume":"34","author":"Hayes","year":"2009","journal-title":"Trends Biochem. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/ncb2021","article-title":"The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of keap1","volume":"12","author":"Komatsu","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cotox.2016.09.005","article-title":"Regulation of the keap1\u2013Nrf2 pathway by p62\/sqstm1","volume":"1","author":"Katsuragi","year":"2016","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.niox.2011.06.001","article-title":"Nitric oxide activates Nrf2 through s-nitrosylation of keap1 in pc12 cells","volume":"25","author":"Um","year":"2011","journal-title":"Nitric Oxide"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1089\/ars.2012.4645","article-title":"Hydrogen sulfide protects against cellular senescence via s-sulfhydration of keap1 and activation of Nrf2","volume":"18","author":"Yang","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41575-019-0109-y","article-title":"Molecular subtypes of pancreatic cancer","volume":"16","author":"Collisson","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1089\/ars.2017.7342","article-title":"Transcriptional regulation by Nrf2","volume":"29","author":"Tonelli","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"36544","DOI":"10.1074\/jbc.M206530200","article-title":"The keap1 btb\/poz dimerization function is required to sequester Nrf2 in cytoplasm","volume":"277","author":"Zipper","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1128\/MCB.24.16.7130-7139.2004","article-title":"Oxidative stress sensor keap1 functions as an adaptor for cul3-based e3 ligase to regulate proteasomal degradation of Nrf2","volume":"24","author":"Kobayashi","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"8037","DOI":"10.1038\/s41598-018-26269-9","article-title":"C151 in keap1 is the main cysteine sensor for the cyanoenone class of Nrf2 activators, irrespective of molecular size or shape","volume":"8","author":"Muramatsu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.bbadis.2016.11.005","article-title":"Nrf2 signaling pathway: Pivotal roles in inflammation","volume":"1863","author":"Ahmed","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1128\/MCB.01204-10","article-title":"Scf\/\u03b2-trcp promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a keap1-independent manner","volume":"31","author":"Rada","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1101\/gad.238246.114","article-title":"Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis","volume":"28","author":"Wu","year":"2014","journal-title":"Genes Dev."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1128\/MCB.00248-10","article-title":"A noncanonical mechanism of Nrf2 activation by autophagy deficiency: Direct interaction between keap1 and p62","volume":"30","author":"Lau","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"809541","DOI":"10.3389\/fphar.2021.809541","article-title":"Antioxidant activity of fluoxetine and vortioxetine in a non-transgenic animal model of alzheimer\u2019s disease","volume":"12","author":"Caruso","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"108013","DOI":"10.1016\/j.pharmthera.2021.108013","article-title":"Polyphenols and neuroprotection: Therapeutic implications for cognitive decline","volume":"232","author":"Caruso","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12937-016-0186-5","article-title":"The importance of antioxidants which play the role in cellular response against oxidative\/nitrosative stress: Current state","volume":"15","author":"Kurutas","year":"2016","journal-title":"Nutr. J."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1042\/BST20150014","article-title":"Dissecting molecular cross-talk between Nrf2 and nf-\u03bab response pathways","volume":"43","author":"Wardyn","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Saha, S., Buttari, B., Panieri, E., Profumo, E., and Saso, L. (2020). An overview of Nrf2 signaling pathway and its role in inflammation. Molecules, 25.","DOI":"10.3390\/molecules25225474"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nrd1279","article-title":"The ikk nf-kappa b system: A treasure trove for drug development","volume":"3","author":"Karin","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.4049\/jimmunol.172.6.3553","article-title":"Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation","volume":"172","author":"Soares","year":"2004","journal-title":"J. Immunol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.redox.2013.07.005","article-title":"Potential therapeutic effects of the simultaneous targeting of the Nrf2 and nf-\u03bab pathways in diabetic neuropathy","volume":"1","author":"Negi","year":"2013","journal-title":"Redox Biol."},{"key":"ref_162","first-page":"541","article-title":"Peanut arachidin-1 enhances Nrf2-mediated protective mechanisms against tnf-\u03b1-induced icam-1 expression and nf-\u03bab activation in endothelial cells","volume":"41","author":"Chen","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"9786","DOI":"10.1074\/jbc.M414006200","article-title":"Transcriptional activation of the human galphai2 gene promoter through nuclear factor-kappab and antioxidant response elements","volume":"280","author":"Arinze","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"5188","DOI":"10.1182\/blood-2012-04-422121","article-title":"The high Nrf2 expression in human acute myeloid leukemia is driven by nf-\u03bab and underlies its chemo-resistance","volume":"120","author":"Rushworth","year":"2012","journal-title":"Blood"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Senoner, T., and Dichtl, W. (2019). Oxidative stress in cardiovascular diseases: Still a therapeutic target?. Nutrients, 11.","DOI":"10.3390\/nu11092090"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1152\/physiolgenomics.00041.2017","article-title":"Nrf2 at the heart of oxidative stress and cardiac protection","volume":"50","author":"Chen","year":"2018","journal-title":"Physiol. Genom."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s00204-019-02429-2","article-title":"Involvement of Nrf2\/ho-1 antioxidant signaling and nf-\u03bab inflammatory response in the potential protective effects of vincamine against methotrexate-induced nephrotoxicity in rats: Cross talk between nephrotoxicity and neurotoxicity","volume":"93","author":"Shalaby","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e2599","DOI":"10.1038\/cddis.2017.8","article-title":"Thioridazine enhances sensitivity to carboplatin in human head and neck cancer cells through downregulation of c-flip and mcl-1 expression","volume":"8","author":"Seo","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"720620","DOI":"10.3389\/fonc.2021.720620","article-title":"Angelica polysaccharide antagonizes 5-fu-induced oxidative stress injury to reduce apoptosis in the liver through Nrf2 pathway","volume":"11","author":"Zeng","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"7582730","DOI":"10.1155\/2018\/7582730","article-title":"Chemotherapeutic drugs and mitochondrial dysfunction: Focus on doxorubicin, trastuzumab, and sunitinib","volume":"2018","author":"Gorini","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"808480","DOI":"10.3389\/fphar.2021.808480","article-title":"Fisetin attenuates doxorubicin-induced cardiomyopathy in vivo and in vitro by inhibiting ferroptosis through sirt1\/Nrf2 signaling pathway activation","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"8860883","DOI":"10.1155\/2021\/8860883","article-title":"Activation of Nrf2 by mir-152 inhibits doxorubicin-induced cardiotoxicity via attenuation of oxidative stress, inflammation, and apoptosis","volume":"2021","author":"Zhang","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"611087","DOI":"10.3389\/fphar.2020.611087","article-title":"Tanshinone iia: A review of its anticancer effects","volume":"11","author":"Fang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_174","first-page":"3333","article-title":"Nrf2-dependent antioxidant response mediated the protective effect of tanshinone iia on doxorubicin-induced cardiotoxicity","volume":"16","author":"Guo","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/ptr.6882","article-title":"Natural compounds against doxorubicin-induced cardiotoxicity: A review on the involvement of Nrf2\/are signaling pathway","volume":"35","author":"Yarmohammadi","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"e03803","DOI":"10.1016\/j.heliyon.2020.e03803","article-title":"Modulation of Nrf2 by quercetin in doxorubicin-treated rats","volume":"6","author":"Sharma","year":"2020","journal-title":"Heliyon"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"5275","DOI":"10.2147\/DDDT.S281854","article-title":"Edaravone and acetovanillone upregulate Nrf2 and pi3k\/akt\/mtor signaling and prevent cyclophosphamide cardiotoxicity in rats","volume":"14","author":"Hassanein","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"220301","DOI":"10.1088\/0022-3727\/42\/22\/220301","article-title":"Progress in applications of magnetic nanoparticles in biomedicine","volume":"42","year":"2009","journal-title":"J. Phys. D Appl. Phys."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1191\/0960327106ht637oa","article-title":"Comparative study of the protective effect between deferoxamine and deferiprone on chronic iron overload induced cardiotoxicity in rats","volume":"25","author":"Emara","year":"2006","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1177\/0960327117741751","article-title":"Activation of the molecular and functional effects of Nrf2 against chronic iron oxide nanorod overload-induced cardiotoxicity","volume":"37","author":"Elgharabawy","year":"2018","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"103327","DOI":"10.1016\/j.critrevonc.2021.103327","article-title":"Tumor hypoxia: The major culprit behind cisplatin resistance in cancer patients","volume":"162","author":"Devarajan","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pharmthera.2018.04.009","article-title":"Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms","volume":"189","author":"Alexandre","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1039\/D2FO00298A","article-title":"Hesperidin protects against cisplatin-induced cardiotoxicity in mice by regulating the p62-keap1-Nrf2 pathway","volume":"13","author":"Jia","year":"2022","journal-title":"Food Funct."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neuro.2020.10.001","article-title":"Quercetin provides protection against the peripheral nerve damage caused by vincristine in rats by suppressing caspase 3, nf-\u03bab, atf-6 pathways and activating Nrf2, akt pathways","volume":"81","author":"Yardim","year":"2020","journal-title":"Neurotoxicology"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"491","DOI":"10.33549\/physiolres.933939","article-title":"Nociceptive behavior induced by chemotherapeutic paclitaxel and beneficial role of antioxidative pathways","volume":"68","author":"Miao","year":"2019","journal-title":"Physiol. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.freeradbiomed.2010.01.021","article-title":"The Nrf2-heme oxygenase-1 system modulates cyclosporin a-induced epithelial-mesenchymal transition and renal fibrosis","volume":"48","author":"Shin","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Han, H.Y., Choi, M.S., Yoon, S., Ko, J.W., Kim, S.K., and Kim, T.W. (2021). Investigation of ifosfamide toxicity induces common upstreAm. regulator in liver and kidney. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212201"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00702-017-1686-y","article-title":"Epidemiology of parkinson\u2019s disease","volume":"124","author":"Tysnes","year":"2017","journal-title":"J. Neural Transm."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"10774","DOI":"10.1039\/D0FO02165B","article-title":"Isoorientin exerts a protective effect against 6-ohda-induced neurotoxicity by activating the ampk\/akt\/Nrf2 signalling pathway","volume":"11","author":"Ma","year":"2020","journal-title":"Food Funct."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12974-019-1472-x","article-title":"Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner","volume":"16","author":"Zhang","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3389\/fneur.2019.00271","article-title":"Hydralazine protects nigrostriatal dopaminergic neurons from mpp(+) and mptp induced neurotoxicity: Roles of Nrf2-are signaling pathway","volume":"10","author":"Guo","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1021\/acsmedchemlett.8b00270","article-title":"Acrylamide functional group incorporation improves drug-like properties: An example with egfr inhibitors","volume":"10","author":"Wu","year":"2019","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Davuljigari, C.B., Ekuban, F.A., Zong, C., Fergany, A.A.M., Morikawa, K., and Ichihara, G. (2021). Nrf2 activation attenuates acrylamide-induced neuropathy in mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115995"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"152785","DOI":"10.1016\/j.tox.2021.152785","article-title":"Genetic ablation of Nrf2 exacerbates neurotoxic effects of acrylamide in mice","volume":"456","author":"Ekuban","year":"2021","journal-title":"Toxicology"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Gellman, M.D., and Turner, J.R. (2013). Alcohol consumption. Encyclopedia of Behavioral Medicine, Springer.","DOI":"10.1007\/978-1-4419-1005-9"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"115617","DOI":"10.1016\/j.taap.2021.115617","article-title":"Liver-specific Nrf2 deficiency accelerates ethanol-induced lethality and hepatic injury in vivo","volume":"426","author":"Sun","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12974-018-1157-x","article-title":"Acute dose of melatonin via Nrf2 dependently prevents acute ethanol-induced neurotoxicity in the developing rodent brain","volume":"15","author":"Ali","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1002\/cber.19000330275","article-title":"Ueber das carnosin, eine neue organische base des fleischextractes","volume":"33","author":"Gulewitsch","year":"1900","journal-title":"Ber. Dtsch. Chem. Ges."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Caruso, G., Godos, J., Castellano, S., Micek, A., Murabito, P., Galvano, F., Ferri, R., Grosso, G., and Caraci, F. (2021). The therapeutic potential of carnosine\/anserine supplementation against cognitive decline: A systematic review with meta-analysis. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030253"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1016\/S0021-9258(18)69651-6","article-title":"Enzymatic synthesis of carnosine and related \u03b2-alanyl and \u03b3-aminobutyryl peptides","volume":"234","author":"Kalyankar","year":"1959","journal-title":"J. Biol. Chem."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0006-3002(59)90437-8","article-title":"Carnosine-anserine synthetase of muscle i. Preparation and properties of a soluble enyzme from chick muscle","volume":"31","author":"Winnick","year":"1959","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Caruso, G., Musso, N., Grasso, M., Costantino, A., Lazzarino, G., Tascedda, F., Gulisano, M., Lunte, S.M., and Caraci, F. (2020). Microfluidics as a novel tool for biological and toxicological assays in drug discovery processes: Focus on microchip electrophoresis. Micromachines, 11.","DOI":"10.3390\/mi11060593"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/ageing\/29.3.207","article-title":"Carnosine: Physiological properties and therapeutic potential","volume":"29","author":"Gariballa","year":"2000","journal-title":"Age Ageing"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1749-6632.1998.tb09890.x","article-title":"Pluripotent protective effects of carnosine, a naturally occurring dipeptide","volume":"854","author":"Hipkiss","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0009-8981(82)90166-8","article-title":"Human serum carnosinase: Characterization, distinction from cellular carnosinase, and activation by cadmium","volume":"123","author":"Lenney","year":"1982","journal-title":"Clin. Chim. Acta"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1042\/bj2280653","article-title":"Characterization of human tissue carnosinase","volume":"228","author":"Lenney","year":"1985","journal-title":"Biochem. J."},{"key":"ref_207","first-page":"1317","article-title":"Carnosine and anserine in working muscles--study using proton nmr spectroscopy","volume":"57","author":"Dobrota","year":"1992","journal-title":"Biokhimiia"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1007\/s00726-013-1476-2","article-title":"Carnosine: From exercise performance to health","volume":"44","author":"Sale","year":"2013","journal-title":"Amino Acids"},{"key":"ref_209","first-page":"691","article-title":"Effect of carnosine and anserine on action of isolated frog muscles","volume":"91","author":"Severin","year":"1953","journal-title":"Dokl. Akad. Nauk. SSSR"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0306-3623(78)90051-4","article-title":"Localization of carnosine effect on the fatigued muscle preparation","volume":"9","author":"Boldyrev","year":"1978","journal-title":"Gen. Pharmacol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1123\/ijspp.2017-0636","article-title":"\u0392-alanine supplementation\u2019s improvement of high-intensity game activities in water polo","volume":"13","author":"Brisola","year":"2018","journal-title":"Int. J. Sports Physiol. Perform."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jsams.2016.08.014","article-title":"Beta-alanine supplementation enhances judo-related performance in highly-trained athletes","volume":"20","author":"Franchini","year":"2017","journal-title":"J. Sci. Med. Sport"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12970-018-0238-7","article-title":"\u0392-alanine supplementation increased physical performance and improved executive function following endurance exercise in middle aged individuals","volume":"15","author":"Furst","year":"2018","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3177\/jnsv.61.161","article-title":"Effects of acute beta-alanine supplementation on anaerobic performance in trained female cyclists","volume":"61","author":"Glenn","year":"2015","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.neuint.2010.06.001","article-title":"\u0392-alanine as a small molecule neurotransmitter","volume":"57","author":"Tiedje","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Fresta, C.G., Fidilio, A., Lazzarino, G., Musso, N., Grasso, M., Merlo, S., Amorini, A.M., Bucolo, C., Tavazzi, B., and Lazzarino, G. (2020). Modulation of pro-oxidant and pro-inflammatory activities of m1 macrophages by the natural dipeptide carnosine. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030776"},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Caruso, G., Fresta, C.G., Fidilio, A., O\u2019Donnell, F., Musso, N., Lazzarino, G., Grasso, M., Amorini, A.M., Tascedda, F., and Bucolo, C. (2019). Carnosine decreases pma-induced oxidative stress and inflammation in murine macrophages. Antioxidants, 8.","DOI":"10.3390\/antiox8080281"},{"key":"ref_218","first-page":"1378","article-title":"The effect of carnosine on hematopoietic stem cell activity in irradiated animals","volume":"57","author":"Sergienko","year":"1992","journal-title":"Biokhimiia"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.1007\/s00216-017-0401-z","article-title":"Microchip electrophoresis with laser-induced fluorescence detection for the determination of the ratio of nitric oxide to superoxide production in macrophages during inflammation","volume":"409","author":"Caruso","year":"2017","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1039\/C6AY03009B","article-title":"Monitoring carnosine uptake by RAW 264.7 macrophage cells using microchip electrophoresis with fluorescence detection","volume":"9","author":"Fresta","year":"2017","journal-title":"Anal. Methods"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11010-017-2991-3","article-title":"Carnosine modulates nitric oxide in stimulated murine raw 264.7 macrophages","volume":"431","author":"Caruso","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Caruso, G., Benatti, C., Musso, N., Fresta, C.G., Fidilio, A., Spampinato, G., Brunello, N., Bucolo, C., Drago, F., and Lunte, S.M. (2021). Carnosine protects macrophages against the toxicity of a\u03b21-42 oligomers by decreasing oxidative stress. Biomedicines, 9.","DOI":"10.3390\/biomedicines9050477"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"7925","DOI":"10.1128\/AEM.01369-10","article-title":"Antiglycation effects of carnosine and other compounds on the long-term survival of escherichia coli","volume":"76","author":"Pepper","year":"2010","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1023\/A:1020271013277","article-title":"Carnosine, the protective, anti-aging peptide","volume":"19","author":"Boldyrev","year":"1999","journal-title":"Biosci. Rep."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1139\/cjpp-2016-0647","article-title":"Chelating effects of carnosine in ameliorating nickel-induced nephrotoxicity in rats","volume":"95","author":"Hasanein","year":"2017","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/j100489a002","article-title":"Chelation chemistry of carnosine. Evidence that mixed complexes may occur in vivo","volume":"83","author":"Brown","year":"1979","journal-title":"J. Phys. Chem."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.brainresbull.2016.03.019","article-title":"Carnosine decreased neuronal cell death through targeting glutamate system and astrocyte mitochondrial bioenergetics in cultured neuron\/astrocyte exposed to ogd\/recovery","volume":"124","author":"Ouyang","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"17100","DOI":"10.1074\/jbc.RA120.014188","article-title":"Carnosine synthase deficiency is compatible with normal skeletal muscle and olfactory function but causes reduced olfactory sensitivity in aging mice","volume":"295","author":"Bastian","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"102016","DOI":"10.1016\/j.redox.2021.102016","article-title":"Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel carns1 knockout rat model","volume":"44","author":"Sales","year":"2021","journal-title":"Redox Biol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s00726-022-03150-8","article-title":"Absence of endogenous carnosine synthesis does not increase protein carbonylation and advanced lipoxidation end products in brain, kidney or muscle","volume":"54","author":"Becker","year":"2022","journal-title":"Amino Acids"},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Caruso, G. (2022). Unveiling the hidden therapeutic potential of carnosine, a molecule with a multimodal mechanism of action: A position paper. Molecules, 27.","DOI":"10.3390\/molecules27103303"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"44492","DOI":"10.1038\/srep44492","article-title":"Carnosine attenuates the development of both type 2 diabetes and diabetic nephropathy in btbr ob\/ob mice","volume":"7","author":"Albrecht","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1007\/s00726-010-0749-2","article-title":"Vegetarianism, female gender and increasing age, but not cndp1 genotype, are associated with reduced muscle carnosine levels in humans","volume":"40","author":"Everaert","year":"2011","journal-title":"Amino Acids"},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Masuoka, N., Yoshimine, C., Hori, M., Tanaka, M., Asada, T., Abe, K., and Hisatsune, T. (2019). Effects of anserine\/carnosine supplementation on mild cognitive impairment with APOE4. Nutrients, 11.","DOI":"10.3390\/nu11071626"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jad.2020.02.020","article-title":"L-carnosine combination therapy for major depressive disorder: A randomized, double-blind, placebo-controlled trial","volume":"267","author":"Araminia","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.nutres.2017.11.003","article-title":"L-carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products, and tumor necrosis factor-alpha levels in patients with type 2 diabetes: A double-blind placebo-controlled randomized clinical trial","volume":"49","author":"Houjeghani","year":"2018","journal-title":"Nutr. Res."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"913","DOI":"10.3389\/fphys.2020.00913","article-title":"The muscle carnosine response to beta-alanine supplementation: A systematic review with bayesian individual and aggregate data e-max model and meta-analysis","volume":"11","author":"Rezende","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1007\/s11064-008-9775-9","article-title":"Cellular stress response: A novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity","volume":"33","author":"Calabrese","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Calabrese, V., Scuto, M., Salinaro, A.T., Dionisio, G., Modafferi, S., Ontario, M.L., Greco, V., Sciuto, S., Schmitt, C.P., and Calabrese, E.J. (2020). Hydrogen sulfide and carnosine: Modulation of oxidative stress and inflammation in kidney and brain axis. Antioxidants, 9.","DOI":"10.3390\/antiox9121303"},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Smith, R.E., Tran, K., Smith, C.C., McDonald, M., Shejwalkar, P., and Hara, K. (2016). The role of the Nrf2\/are antioxidant system in preventing cardiovascular diseases. Diseases, 4.","DOI":"10.3390\/diseases4040034"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/10715762.2020.1856830","article-title":"Understanding the antioxidant and carbonyl sequestering activity of carnosine: Direct and indirect mechanisms","volume":"55","author":"Aldini","year":"2021","journal-title":"Free Radic. Res."},{"key":"ref_242","unstructured":"Boldyrev, A.A. (2007). Carnosine and Oxidative Stress in Cells and Tissues, Nova Publishers."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1113\/jphysiol.1991.sp018673","article-title":"Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose","volume":"439","author":"Gardner","year":"1991","journal-title":"J. Physiol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1519\/JSC.0b013e3181bac43c","article-title":"Hormonal responses to resistance exercise after ingestion of carnosine and anserine","volume":"25","author":"Goto","year":"2011","journal-title":"J. Strength Cond. Res."},{"key":"ref_245","first-page":"112","article-title":"Investigation of dose-related effects of carnosine on anxiety with sympathetic skin response and t-maze","volume":"57","author":"Dolu","year":"2014","journal-title":"Acta Med."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00726-011-1169-7","article-title":"Effect of slow-release \u03b2-alanine tablets on absorption kinetics and paresthesia","volume":"43","author":"Beaumont","year":"2012","journal-title":"Amino Acids"},{"key":"ref_247","doi-asserted-by":"crossref","unstructured":"Salatto, R.W., McGinnis, G.R., Davis, D.W., Carrier, B., Manning, J.W., DeBeliso, M., and Navalta, J.W. (2021). Effects of acute beta-alanine ingestion and immersion-plus-exercise on connectedness to nature and perceived pain. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18158134"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"103827","DOI":"10.1016\/j.isci.2022.103827","article-title":"Nrf2 activation reprograms macrophage intermediary metabolism and suppresses the type i interferon response","volume":"25","author":"Ryan","year":"2022","journal-title":"iScience"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1684\/ecn.2016.0372","article-title":"Protective effects of l-carnosine on ccl4 -induced hepatic injury in rats","volume":"27","author":"Alsheblak","year":"2016","journal-title":"Eur. Cytokine Netw."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.4239\/wjd.v6.i13.1246","article-title":"Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research","volume":"6","author":"Leon","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.peptides.2016.10.008","article-title":"Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms","volume":"86","author":"Zamani","year":"2016","journal-title":"Peptides"},{"key":"ref_252","first-page":"1079","article-title":"Influence of carnosine on the cardiotoxicity of doxorubicin in rabbits","volume":"55","author":"Zieba","year":"2003","journal-title":"Pol. J. Pharmacol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"4348973","DOI":"10.1155\/2019\/4348973","article-title":"Carnosine protects mouse podocytes from high glucose induced apoptosis through pi3k\/akt and Nrf2 pathways","volume":"2019","author":"Zhao","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Scuto, M., Trovato Salinaro, A., Modafferi, S., Polimeni, A., Pfeffer, T., Weigand, T., Calabrese, V., Schmitt, C.P., and Peters, V. (2020). Carnosine activates cellular stress response in podocytes and reduces glycative and lipoperoxidative stress. Biomedicines, 8.","DOI":"10.3390\/biomedicines8060177"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1139\/cjpp-2020-0212","article-title":"Synergistic effect of aminoguanidine and l-carnosine against thioacetamide-induced hepatic encephalopathy in rats: Behavioral, biochemical, and ultrastructural evidence","volume":"99","author":"Afifi","year":"2021","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.pneurobio.2018.12.004","article-title":"Pivotal role of carnosine in the modulation of brain cells activity: Multimodal mechanism of action and therapeutic potential in neurodegenerative disorders","volume":"175","author":"Caruso","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"227","DOI":"10.12998\/wjcc.v10.i1.227","article-title":"Zinc carnosine-based modified bismuth quadruple therapy vs. standard triple therapy for helicobacter pylori eradication: A randomized controlled study","volume":"10","author":"Ibrahim","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2147\/IJN.S341216","article-title":"Study on the local anti-osteoporosis effect of polaprezinc-loaded antioxidant electrospun membrane","volume":"17","author":"Gao","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.taap.2018.12.015","article-title":"L-carnosine protects against oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting nrf-2 and nf-\u03bab pathways","volume":"365","author":"Yehia","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/14\/4452\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:48:52Z","timestamp":1760140132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/14\/4452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,12]]},"references-count":259,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["molecules27144452"],"URL":"https:\/\/doi.org\/10.3390\/molecules27144452","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,12]]}}}