title: Carnosic acid attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity.
abstract: Nephrotoxicity is one of the serious dose limiting side effects of cisplatin when used in the treatment of various malignant conditions. Accumulating evidence suggests that oxidative stress caused by free radicals and apoptosis of renal cells contributes to the pathogenesis of cisplatin-induced nephrotoxicity. Present study was aimed to explore the effect of carnosic acid, a potent antioxidant, against cisplatin induced oxidative stress and nephrotoxicity in rats. A single dose of cisplatin (7.5mg/kg) caused marked renal damage, characterized by a significant (P<0.05) increase in serum creatinine, blood urea nitrogen (BUN) and relative weight of kidney with higher kidney MDA (malondialdehyde), tROS (total reactive oxygen species), caspase 3, GSH (reduced glutathione) levels and lowered tissue nitrite, SOD (superoxide dismutase), CAT (catalase), GSH-Px (glutathione peroxidase), GR (glutathione reductase) and GST (glutathione S-transferase) levels compared to normal control. Carnosic acid treatment significantly (P<0.05) attenuated the increase in lipid peroxidation, caspase-3 and ROS generation and enhanced the levels of reduced glutathione, tissue nitrite level and activities of SOD, CAT, GSH-Px, GR and GST compared to cisplatin control. The present study demonstrates that carnosic acid has a protective effect on cisplatin induced experimental nephrotoxicity and is attributed to its potent antioxidant and antiapoptotic properties.
authors.affiliation: National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad, India.
authors.forename: Bidya Dhar
authors.initials: BD
authors.lastname: Sahu
authors.forename: Kiran Kumar Reddy
authors.initials: KK
authors.lastname: Rentam
authors.forename: Uday Kumar
authors.initials: UK
authors.lastname: Putcha
authors.forename: Madhusudana
authors.initials: M
authors.lastname: Kuncha
authors.forename: Ganga Modi Naidu
authors.initials: GM
authors.lastname: Vegi
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D045784:Abietanes; D000970:Antineoplastic Agents; D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; C018381:salvin; D002945:Cisplatin