{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:56:21Z","timestamp":1778856981720,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","award":["Fast-track Research Funding Program"],"award-info":[{"award-number":["Fast-track Research Funding Program"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Renal toxicity is a serious side effect that hinders the use of cisplatin, a commonly used and effective chemotherapeutic agent. Meanwhile, quinacrine is an FDA approved drug that has been stated for its anti-inflammatory effect. Thus, we investigated the ameliorative effect of quinacrine against cisplatin-induced renal toxicity. Single intraperitoneal (i.p.) 10 mg\/kg cisplatin administration induced renal injury in rats. Our results showed that 10 mg\/kg\/day quinacrine decreased the mortality rate of rats from 46.15% (cisplatin group) to 12.5%, and significantly decreased renal tissue fibrosis, relative kidney to body weight ratio, serum creatinine and urea levels compared with the cisplatin group. Indeed, quinacrine significantly decreased renal malondialdehyde concentration and increased renal total antioxidant capacity, compared with the cisplatin group. Furthermore, quinacrine caused significant upregulation of renal sirtuin-1 (SIRT-1) with significant downregulation of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-\u03b1 (TNF-\u03b1). Moreover, quinacrine significantly blocked cisplatin-induced apoptosis, which was made evident by downregulating renal apoptotic proteins (BAX and p53) and upregulating the renal anti-apoptotic protein BCL2, compared with the cisplatin group. In conclusion, this study demonstrates, for the first time, that quinacrine alleviates cisplatin-induced renal toxicity via upregulating SIRT-1, downregulating inflammatory markers (ICAM-1 and TNF-\u03b1), reducing oxidative stress, and inhibiting apoptosis.<\/jats:p>","DOI":"10.3390\/ijms221910660","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T10:55:40Z","timestamp":1633085740000},"page":"10660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Quinacrine Ameliorates Cisplatin-Induced Renal Toxicity via Modulation of Sirtuin-1 Pathway"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-2802","authenticated-orcid":false,"given":"Nada F.","family":"Abo El-Magd","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hasnaa Ali","family":"Ebrahim","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh 11564, Saudi Arabia"},{"name":"Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-1743","authenticated-orcid":false,"given":"Mohamed","family":"El-Sherbiny","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 13713, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nada H.","family":"Eisa","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0079-6603(01)67026-0","article-title":"Cisplatin: From DNA damage to cancer chemotherapy","volume":"67","author":"Cohen","year":"2001","journal-title":"Prog. Nucleic Acid Res. Mol. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/sj.ki.5002786","article-title":"Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies","volume":"73","author":"Pabla","year":"2008","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrd1691","article-title":"Cellular processing of platinum anticancer drugs","volume":"4","author":"Wang","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1080\/26895293.2020.1760149","article-title":"N6-2-hydroxyethyl-adenosine ameliorate cisplatin induced acute kidney injury in mice","volume":"13","author":"Yin","year":"2020","journal-title":"All Life"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"F881","DOI":"10.1152\/ajprenal.00192.2013","article-title":"Increasing cGMP-dependent protein kinase I activity attenuates cisplatin-induced kidney injury through protection of mitochondria function","volume":"305","author":"Maimaitiyiming","year":"2013","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1096\/fj.12-218040","article-title":"Novel orally active epoxyeicosatrienoic acid (EET) analogs attenuate cisplatin nephrotoxicity","volume":"27","author":"Khan","year":"2013","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ebiom.2018.09.031","article-title":"Celastrol ameliorates cisplatin nephrotoxicity by inhibiting NF-\u03baB and improving mitochondrial function","volume":"36","author":"Yu","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.intimp.2016.09.020","article-title":"Hyperin inhibits nuclear factor kappa B and activates nuclear factor E2-related factor-2 signaling pathways in cisplatin-induced acute kidney injury in mice","volume":"40","author":"Chao","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7912763","DOI":"10.1155\/2020\/7912763","article-title":"Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4\/NF-\u03baB\/MAPK and Activating the HO-1\/Nrf2 and Sirt-1\/AMPK Pathways in Mice","volume":"2020","author":"Deng","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"F427","DOI":"10.1152\/ajprenal.00258.2010","article-title":"SIRT1 activation by resveratrol ameliorates cisplatin-induced renal injury through deacetylation of p53","volume":"301","author":"Kim","year":"2011","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kim, J.-Y., Jo, J., Kim, K., An, H.-J., Gwon, M.-G., Gu, H., Kim, H.-J., Yang, A.Y., Kim, S.-W., and Jeon, E.J. (2019). Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice. Antioxidants, 8.","DOI":"10.3390\/antiox8080322"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1615\/IntJMedMushrooms.2019030329","article-title":"Comparison of Chemical Compositions, Bioactive Ingredients, and In Vitro Antitumor Activity of Four Products of Cordyceps (Ascomycetes) Strains from China","volume":"21","author":"Qiao","year":"2019","journal-title":"Int. J. Med. Mushrooms"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.semcancer.2019.09.021","article-title":"Repurposing quinacrine for treatment-refractory cancer","volume":"68","author":"Oien","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e000430","DOI":"10.1136\/lupus-2020-000430","article-title":"Candidate drug replacements for quinacrine in cutaneous lupus erythematosus","volume":"7","author":"Yan","year":"2020","journal-title":"Lupus Sci. Med."},{"key":"ref_15","first-page":"829","article-title":"Use of antimalarials in dermatology","volume":"8","author":"Ochsendorf","year":"2010","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cyto.2015.10.010","article-title":"Renal protective effects of arjunolic acid in a cisplatin-induced nephrotoxicity model","volume":"77","author":"Elsherbiny","year":"2016","journal-title":"Cytokine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cbi.2019.05.029","article-title":"Wogonin pre-treatment attenuates cisplatin-induced nephrotoxicity in rats: Impact on PPAR-\u03b3, inflammation, apoptosis and Wnt\/\u03b2-catenin pathway","volume":"308","author":"Badawy","year":"2019","journal-title":"Chem.-Biol. Interact."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.cbi.2018.11.008","article-title":"Omeprazole protects against cisplatin-induced nephrotoxicity by alleviating oxidative stress, inflammation, and transporter-mediated cisplatin accumulation in rats and HK-2 cells","volume":"297","author":"Gao","year":"2019","journal-title":"Chem.-Biol. Interact."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.fct.2018.02.041","article-title":"Astilbin ameliorates cisplatin-induced nephrotoxicity through reducing oxidative stress and inflammation","volume":"114","author":"Wang","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/00007890-199608270-00001","article-title":"Quinacrine Attenuates Cyclosporine-Induced Nephrotoxicity in Rats1","volume":"62","author":"Khader","year":"1996","journal-title":"Transplantation"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Al Asmari, A.K., Al Sadoon, K.T., Obaid, A.A., Yesunayagam, D., and Tariq, M. (2017). Protective effect of quinacrine against glycerol-induced acute kidney injury in rats. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0450-8"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"52928","DOI":"10.18632\/oncotarget.10608","article-title":"Repurposing the anti-malarial drug, quinacrine: New anti-colitis properties","volume":"7","author":"Chumanevich","year":"2016","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"630509","DOI":"10.1155\/2014\/630509","article-title":"The effects of quinacrine, proglumide, and pentoxifylline on seizure activity, cognitive deficit, and oxidative stress in rat lithium-pilocarpine model of status epilepticus","volume":"2014","author":"Ahmad","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1097\/00001756-200309150-00017","article-title":"Quinacrine acts as an antioxidant and reduces the toxicity of the prion peptide PrP106-126","volume":"14","author":"Turnbull","year":"2003","journal-title":"Neuroreport"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1517\/14728222.2012.648926","article-title":"SIRT1: New avenues of discovery for disorders of oxidative stress","volume":"16","author":"Chong","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Qi, Z., Li, Z., Li, W., Liu, Y., Wang, C., Lin, H., Liu, J., and Li, P. (2018). Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1\/NF-\u03baB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice. Molecules, 23.","DOI":"10.3390\/molecules23113038"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e22738","DOI":"10.1002\/jbt.22738","article-title":"Nephroprotective effect of umbelliferone against cisplatin-induced kidney damage is mediated by regulation of NRF2, cytoglobin, SIRT1\/FOXO-3, and NF- kB-p65 signaling pathways","volume":"35","author":"Ali","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.3390\/toxins2112490","article-title":"Mechanisms of Cisplatin nephrotoxicity","volume":"2","author":"Miller","year":"2010","journal-title":"Toxins"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.taap.2013.10.031","article-title":"Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis","volume":"274","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1172\/JCI200215606","article-title":"TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity","volume":"110","author":"Ramesh","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1620\/tjem.229.195","article-title":"D-ribose ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice","volume":"229","author":"Ueki","year":"2013","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Harada, M., Morimoto, K., Kondo, T., Hiramatsu, R., Okina, Y., Muko, R., Matsuda, I., and Kataoka, T. (2017). Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-\u03baB Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF-\u03b1 and the Fas Ligand. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122603"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S57","DOI":"10.1016\/j.jisp.2016.11.001","article-title":"Quinacrine Suppresses Tumor Necrosis Factor-\u03b1 and IFN-\u03b1 in Dermatomyositis and Cutaneous Lupus Erythematosus","volume":"18","author":"Alves","year":"2017","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8506195","DOI":"10.1155\/2019\/8506195","article-title":"The Beneficial Roles of SIRT1 in Drug-Induced Liver Injury","volume":"2019","author":"Yan","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1007\/s11033-020-05582-5","article-title":"Metformin and\/or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1\/SOD and BAX\/Bcl-2 pathways in rats","volume":"47","author":"Omran","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/CAD.0000000000000824","article-title":"EX527, a Sirt-1 inhibitor, induces apoptosis in glioma via activating the p53 signaling pathway","volume":"31","author":"Wang","year":"2020","journal-title":"Anti-Cancer Drugs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jphotobiol.2016.03.027","article-title":"Hepatoprotective effect of grape seed oil against carbon tetrachloride induced oxidative stress in liver of \u03b3-irradiated rat","volume":"160","author":"Ismail","year":"2016","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6376","DOI":"10.1158\/1078-0432.CCR-08-1526","article-title":"Structural and Functional Basis for Therapeutic Modulation of p53 Signaling","volume":"14","author":"Bassett","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nature09852","article-title":"Catalytic activity of the caspase-8\u2013FLIP L complex inhibits RIPK3-dependent necrosis","volume":"471","author":"Oberst","year":"2011","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1084\/jem.20110251","article-title":"Mechanisms of necroptosis in T cells","volume":"208","author":"Tsau","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1023\/A:1007546505528","article-title":"Involvement of phospholipase A2 activation in anthrax lethal toxin-induced cytotoxicity","volume":"15","author":"Shin","year":"1999","journal-title":"Cell Biol. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.fct.2012.11.015","article-title":"Merit of quinacrine in the decrease of ingested sulfite-induced toxic action in rat brain","volume":"52","author":"Kencebay","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10495-015-1190-5","article-title":"Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity","volume":"21","author":"Pessoa","year":"2016","journal-title":"Apoptosis"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4103\/0974-8490.172658","article-title":"Ameliorative Effects of Chloroform Fraction of Cocos nucifera L. Husk Fiber Against Cisplatin-induced Toxicity in Rats","volume":"8","author":"Adaramoye","year":"2016","journal-title":"Pharmacogn. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neulet.2006.11.029","article-title":"The effects of the glucocorticoid receptor antagonist RU486 and phospholipase A2 inhibitor quinacrine on acoustic injury of the mouse cochlea","volume":"413","author":"Hirose","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0009-8981(72)90432-9","article-title":"Serum creatinine determination without protein precipitation","volume":"37","author":"Bartels","year":"1972","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1136\/jcp.13.2.156","article-title":"A rapid and precise method for the determination of urea","volume":"13","author":"Fawcett","year":"1960","journal-title":"J. Clin. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0009-8981(78)90081-5","article-title":"Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method","volume":"90","author":"Kei","year":"1978","journal-title":"Clin. Chim. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1136\/jcp.54.5.356","article-title":"Method for the measurement of antioxidant activity in human fluids","volume":"54","author":"Koracevic","year":"2001","journal-title":"J. Clin. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:08:23Z","timestamp":1760166503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":49,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910660"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910660","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]}}}