{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T21:01:13Z","timestamp":1788037273296,"version":"build-2784847793"},"reference-count":70,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology, New Delhi, India","award":["DST\/INSPIRE Fellowship\/2014\/IF170036"],"award-info":[{"award-number":["DST\/INSPIRE Fellowship\/2014\/IF170036"]}]},{"name":"Council of Scientific &amp; Industrial Research, New Delhi, India","award":["02(0275)\/16\/EMR-II"],"award-info":[{"award-number":["02(0275)\/16\/EMR-II"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl2 in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p &lt; 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p &lt; 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-\u03baB\/PKC-\u03b4\/TNFR2 activation. In addition, CdCl2 induced renal fibrosis by triggering TGF-\u03b21\/SMAD3\/\u03b1-SMA\/collagen signaling within renal cells. On the other hand, RA significantly (p &lt; 0.05\u20130.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p &lt; 0.05\u20130.01) reciprocate Cd-mediated pathological changes in blood and urine parameters in mice. In addition, histological data supported the pharmacological findings. In silico chemometric analyses predicted the possible interactions between RA and different signal proteins and anticipated drug-likeness characteristics of RA. Hence, RA can potentially be applied as a therapeutic agent to treat Cd-mediated nephrotoxicity in future.<\/jats:p>","DOI":"10.3390\/ijms20082027","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T03:39:02Z","timestamp":1556163542000},"page":"2027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis"],"prefix":"10.3390","volume":"20","author":[{"given":"Swarnalata","family":"Joardar","sequence":"first","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9085-4226","authenticated-orcid":false,"given":"Saikat","family":"Dewanjee","sequence":"additional","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8379-8286","authenticated-orcid":false,"given":"Shovonlal","family":"Bhowmick","sequence":"additional","affiliation":[{"name":"Department of Chemical Technology, University of Calcutta, Kolkata 700009, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarun K.","family":"Dua","sequence":"additional","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2696-2972","authenticated-orcid":false,"given":"Sonjit","family":"Das","sequence":"additional","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0205-7719","authenticated-orcid":false,"given":"Achintya","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Chemical Technology, University of Calcutta, Kolkata 700009, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1070-3207","authenticated-orcid":false,"given":"Vincenzo","family":"De Feo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12967-015-0598-6","article-title":"The effects of two common edible herbs, Ipomoea aquatica and Enhydra fluctuans, on cadmium-induced pathophysiology: A focus on oxidative defence and anti-apoptotic mechanism","volume":"13","author":"Dua","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.atmosenv.2016.01.030","article-title":"Mid-twentieth century increases in anthropogenic Pb, Cd and Cu in central Asia set in hemispheric perspective using Tien Shan ice core","volume":"131","author":"Grigholm","year":"2016","journal-title":"Atmos. Environ."},{"key":"ref_3","first-page":"135","article-title":"Cadmium toxicity and treatment: An update","volume":"8","author":"Kazemi","year":"2017","journal-title":"Casp. J. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29989","DOI":"10.1038\/srep29989","article-title":"Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function","volume":"6","author":"Wu","year":"2016","journal-title":"Sci Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1124\/jpet.110.166769","article-title":"Mechanisms of cadmium-induced proximal tubule injury: New insights with implications for biomonitoring and therapeutic interventions","volume":"343","author":"Prozialeck","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.fct.2013.07.043","article-title":"Cadmium induced pathophysiology: Prophylactic role of edible jute (Corchorus olitorius) leaves with special emphasis on oxidative stress and mitochondrial involvement","volume":"60","author":"Dewanjee","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1007\/s11356-016-7953-x","article-title":"Treatment of cadmium-induced renal oxidative damage in rats by administration of alpha-lipoic acid","volume":"24","author":"Luo","year":"2017","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.freeradbiomed.2008.04.041","article-title":"Cadmium generates reactive oxygen- and carbon-centered radical species in rats: Insights from in vivo spin-trapping studies","volume":"45","author":"Liu","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.freeradbiomed.2013.08.167","article-title":"Cadmium exposure induces vascular injury due to endothelial oxidative stress: The role of local angiotensin II and COX-2","volume":"65","author":"Angeli","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3892\/ijmm.2016.2640","article-title":"NF-kappaB signaling maintains the survival of cadmium-exposed human renal glomerular endothelial cells","volume":"38","author":"Zhang","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.fct.2016.07.030","article-title":"Epigallocatechin-3-gallate attenuates cadmium-induced chronic renal injury and fibrosis","volume":"96","author":"Chen","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dua, T.K., Dewanjee, S., Khanra, R., Joardar, S., Barma, S., Das, S., Zia-Ul-Haq, M., and De Feo, V. (2016). Cytoprotective and Antioxidant Effects of an Edible Herb, Enhydra fluctuans Lour. (Asteraceae), against Experimentally Induced Lead Acetate Intoxication. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148757"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.5507\/bp.2003.020","article-title":"Metal-chelating properties, electrochemical behavior, scavenging and cytoprotective activities of six natural phenolics","volume":"147","year":"2003","journal-title":"Biomed. Pap."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.enzmictec.2014.07.006","article-title":"Signal transducer and oxidative stress mediated modulation of phenylpropanoid pathway to enhance rosmarinic acid biosynthesis in fungi elicited whole plant culture of Solenostemon scutellarioides","volume":"66","author":"Dewanjee","year":"2014","journal-title":"Enzym. Microb. Technol."},{"key":"ref_15","first-page":"1799","article-title":"Therapeutic and nutraceutical potential of rosmarinic acid-Cytoprotective properties and pharmacokinetic profile","volume":"57","author":"Nunes","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.2174\/1389450116666150506114336","article-title":"Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium","volume":"17","author":"Malgorzata","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9162946","DOI":"10.1155\/2018\/9162946","article-title":"Flavocoxid, a natural antioxidant, protects mouse kidney from cadmium-induced toxicity","volume":"2018","author":"Micali","year":"2018","journal-title":"Oxid Med. Cell. Longev."},{"key":"ref_18","first-page":"313","article-title":"Mangiferin attenuates oxidative stress induced renal cell damage through activation of PI3K induced Akt and Nrf-2 mediated signaling pathways","volume":"5","author":"Saha","year":"2016","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1080\/10715760500231836","article-title":"Rosmarinic acid inhibits the formation of reactive oxygen and nitrogen species in RAW264.7 macrophages","volume":"39","author":"Qiao","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Revoltella, S., Baraldo, G., Waltenberger, B., Schwaiger, S., Kofler, P., Moesslacher, J., Huber-Seidel, A., Pagitz, K., Kohl, R., and Jansen-Duerr, P. (2018). Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus. Molecules, 23.","DOI":"10.3390\/molecules23030653"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.tiv.2017.01.016","article-title":"Antioxidant activity of rosmarinic acid and its principal metabolites in chemical and cellular systems: Importance of physico-chemical characteristics","volume":"40","author":"Chan","year":"2017","journal-title":"Toxicol. In Vitro"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1016\/j.fct.2009.07.038","article-title":"Antidiabetic activity of Diospyros peregrina fruit: Effect on hyperglycemia, hyperlipidemia and augmented oxidative stress in experimental type 2 diabetes","volume":"47","author":"Dewanjee","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/iub.1017","article-title":"Glucose-6-phosphate dehydrogenase, NADPH, and cell survival","volume":"64","author":"Stanton","year":"2012","journal-title":"IUBMB Life"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4062\/biomolther.2015.069","article-title":"Rosmarinic acid attenuates cell damage against UVB radiation-induced oxidative stress via enhancing antioxidant effects in human HaCaT cells","volume":"24","author":"Fernando","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ding, Y., Zhang, Z., Yue, Z., Ding, L., Zhou, Y., Huang, Z., and Huang, H. (2018). Rosmarinic acid ameliorates H2O2-induced oxidative stress in L02 cells through MAPK and Nrf2 pathways. Rejuvenation Res.","DOI":"10.1089\/rej.2018.2107"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.pneurobio.2012.09.003","article-title":"Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection","volume":"100","author":"Zhang","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3389\/fphar.2017.00251","article-title":"Protocatechuic Acid, a phenolic from Sansevieria roxburghiana Leaves, suppresses diabetic cardiomyopathy via stimulating glucose metabolism, ameliorating oxidative stress, and inhibiting inflammation","volume":"8","author":"Bhattacharjee","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_28","first-page":"2977","article-title":"Activation of apoptosis signalling pathways by reactive oxygen species","volume":"1863","year":"2016","journal-title":"BBA Mol. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.biopha.2017.07.112","article-title":"Taraxerol, a pentacyclic triterpenoid, from Abroma augusta leaf attenuates diabetic nephropathy in type 2 diabetic rats","volume":"94","author":"Khanra","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"21353","DOI":"10.1074\/jbc.M511052200","article-title":"Bcl-2 Phosphorylation by p38 MAPK: Identification of target sites and biologic consequences","volume":"281","author":"Marcocci","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.tcb.2015.12.002","article-title":"TNF and ROS Crosstalk in Inflammation","volume":"26","author":"Blaser","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.4049\/jimmunol.180.5.3072","article-title":"The Fas death signaling pathway connecting reactive oxygen species generation and flice inhibitory protein down-regulation","volume":"180","author":"Wang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.bbamcr.2011.01.026","article-title":"Caspase-8 and bid: Caught in the act between death receptors and mitochondria","volume":"1813","author":"Kantari","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1016\/j.cellsig.2014.08.011","article-title":"TRAF-mediated modulation of NF-kB AND JNK activation by TNFR2","volume":"26","author":"Rodriguez","year":"2014","journal-title":"Cell Signal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10697","DOI":"10.3390\/ijms130910697","article-title":"Cell signaling through protein kinase C oxidation and activation","volume":"13","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bcp.2018.06.017","article-title":"MicroRNA: A new generation therapeutic target in diabetic nephropathy","volume":"155","author":"Dewanjee","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/abbs\/gmp018","article-title":"Regulation of TGF-\u03b2 signaling by Smad7","volume":"41","author":"Yan","year":"2009","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejphar.2016.08.022","article-title":"Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update","volume":"791","author":"Bhattacharjee","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","first-page":"5878","article-title":"Effects of bradykinin on TGFbeta1induced epithelialmesenchymal transition in ARPE19 cells","volume":"17","author":"Wei","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/jcp.20972","article-title":"Therapies for bleomycin induced lung fibrosis through regulation of TGF-beta1 induced collagen gene expression","volume":"211","author":"Cutroneo","year":"2007","journal-title":"J. Cell Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.5527\/wjn.v4.i1.83","article-title":"Lipid abnormalities in kidney disease and management strategies","volume":"4","author":"Pandya","year":"2015","journal-title":"World J. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000488816","article-title":"Disorders of Lipid Metabolism in Chronic Kidney Disease","volume":"46","author":"Bulbul","year":"2018","journal-title":"Blood Purif."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"382918","DOI":"10.1155\/2015\/382918","article-title":"Uric Acid as a Marker of Kidney Disease: Review of the Current Literature","volume":"2015","author":"Giordano","year":"2015","journal-title":"Dis. Markers"},{"key":"ref_44","unstructured":"Higgins, C. (2016, October 10). Urea and Creatinine Concentration, the Urea: Creatinine Ratio. Available online: www.acutecaretesting.org."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tojo, A., and Kinugasa, S. (2012). Mechanisms of glomerular albumin filtration and tubular reabsorption. Int. J. Nephrol., 481520.","DOI":"10.1155\/2012\/481520"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"52629","DOI":"10.18632\/oncotarget.17539","article-title":"Antagonistic effects of selenium on cadmium-induced apoptosis by restoring the mitochondrial dynamic equilibrium and energy metabolism in chicken spleens","volume":"8","author":"Xu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Dewanjee, S., Dua, T.K., Khanra, R., Das, S., Barma, S., Joardar, S., Bhattacharjee, N., Zia-Ul-Haq, M., and Jaafar, H.Z. (2015). Water Spinach, Ipomoea aquatica (Convolvulaceae), Ameliorates Lead Toxicity by Inhibiting Oxidative Stress and Apoptosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139831"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Liu, T., Zhang, L., Joo, D., and Sun, S.C. (2017). NF-kappaB signaling in inflammation. Signal Transduct. Target Ther., 2.","DOI":"10.1038\/sigtrans.2017.23"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1421438","DOI":"10.1155\/2018\/1421438","article-title":"Carnosic Acid, a natural diterpene, attenuates arsenic-induced hepatotoxicity via reducing oxidative stress, MAPK activation, and apoptotic cell death pathway","volume":"2018","author":"Das","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_50","unstructured":"Public Health Service (2015). Public Health Service Policy on Human Care and Use of Laboratory Animals, National Institute of Health."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4161\/oxim.1.1.6491","article-title":"Primary mouse renal tubular epithelial cells have variable injury tolerance to ischemic and chemical mediators of oxidative stress","volume":"1","author":"Breggia","year":"2008","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4857","DOI":"10.1016\/j.biomaterials.2011.03.048","article-title":"The protective role of arjunolic acid against doxorubicin induced intracellular ROS dependent JNK-p38 and p53-mediated cardiac apoptosis","volume":"32","author":"Ghosh","year":"2011","journal-title":"Biomaterials"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000066298","article-title":"Delayed apoptosis post-cadmium injury in renal proximal tubule epithelial cells","volume":"23","author":"Stinson","year":"2003","journal-title":"Am. J. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.jep.2013.06.051","article-title":"Monoterpene bisindole alkaloids, from the African medicinal plant Tabernaemontana elegans, induce apoptosis in HCT116 human colon carcinoma cells","volume":"149","author":"Mansoor","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.fct.2017.05.002","article-title":"Edible leaf extract of Ipomoea aquatica Forssk. (Convolvulaceae) attenuates doxorubicin-induced liver injury via inhibiting oxidative impairment, MAPK activation and intrinsic pathway of apoptosis","volume":"105","author":"Dewanjee","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1002\/jcb.24578","article-title":"L-cysteine and hydrogen sulfide increase PIP3 and AMPK\/PPARgamma expression and decrease ROS and vascular inflammation markers in high glucose treated human U937 monocytes","volume":"114","author":"Manna","year":"2013","journal-title":"J. Cell Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0891-5849(88)90023-8","article-title":"Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: Characterization and comparison with homogenates and microsomes","volume":"4","author":"Fraga","year":"1988","journal-title":"Free Radic. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.freeradbiomed.2003.09.020","article-title":"Source of early reactive oxygen species in the apoptosis induced by transforming growth factor-beta in fetal rat hepatocytes","volume":"36","author":"Herrera","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.tox.2011.03.006","article-title":"Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro","volume":"283","author":"Pal","year":"2011","journal-title":"Toxicology"},{"key":"ref_60","first-page":"446","article-title":"Uptake of dietary coenzyme Q supplement is limited in rats","volume":"125","author":"Zhang","year":"1995","journal-title":"J. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.tox.2008.12.008","article-title":"Protective role of arjunolic acid in response to streptozotocin-induced type-I diabetes via the mitochondrial dependent and independent pathways","volume":"257","author":"Manna","year":"2009","journal-title":"Toxicology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/0003-2697(76)90326-2","article-title":"A fluorometric method for determination of oxidized and reduced glutathione in tissues","volume":"74","author":"Hissin","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.mex.2015.11.001","article-title":"Sequential fractionation and isolation of subcellular proteins from tissue or cultured cells","volume":"2","author":"Baghirova","year":"2015","journal-title":"MethodsX"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12967-014-0364-1","article-title":"Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response","volume":"13","author":"Khanra","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.lfs.2006.10.013","article-title":"Cytoprotective and antioxidant role of diallyl tetrasulfide on cadmium induced renal injury: An in vivo and in vitro study","volume":"80","author":"Pari","year":"2007","journal-title":"Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_67","unstructured":"(2018, October 10). OSIRIS Property Explorer. Available online: www.organic-chemistry.org\/prog\/peo\/."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic. Acids Res."},{"key":"ref_69","unstructured":"(2018, October 10). Protein Data Bank. Available online: http:\/\/www.rcsb.org\/."},{"key":"ref_70","unstructured":"(2018, October 10). Maestro, Schr\u00f6dinger, LLC, New York, USA, 2017. Available online: www.schrodinger.com."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/8\/2027\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:46:57Z","timestamp":1760186817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/8\/2027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,24]]},"references-count":70,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["ijms20082027"],"URL":"https:\/\/doi.org\/10.3390\/ijms20082027","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,24]]}}}