title: Metformin Protects Against Cisplatin-Induced Tubular Cell Apoptosis and Acute Kidney Injury via AMPKα-regulated Autophagy Induction.
abstract: Metformin, one of the most common prescriptions for patients with type 2 diabetes, is reported to protect the kidney from gentamicin-induced nephrotoxicity. However, the role and mechanisms for metformin in preventing cisplatin-induced nephrotoxicity remains largely unknown. In this study, a single intraperitoneal injection of cisplatin was employed to induce acute kidney injury (AKI) in CD1 mice. The mice exhibited severe kidney dysfunction and histological damage at day 2 after cisplatin injection. Pretreatment of metformin could markedly attenuate cisplatin-induced acute kidney injury, tubular cell apoptosis and inflammatory cell accumulation in the kidneys. Additionally, pretreatment of metformin could enhance both AMPKα phosphorylation and autophagy induction in the kidneys after cisplatin injection. In cultured NRK-52E cells, a rat kidney tubular cell line, metformin could stimulate AMPKα phosphorylation, induce autophagy and inhibit cisplatin-induced cell apoptosis. Blockade of either AMPKα activation or autophagy induction could largely abolish the protective effect of metformin in cisplatin-induced cell death. Together, this study demonstrated that metformin may protect against cisplatin-induced tubular cell apoptosis and AKI through stimulating AMPKα activation and autophagy induction in the tubular cells.
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gui
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Jiafa
authors.initials: J
authors.lastname: Ren
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Weichun
authors.initials: W
authors.lastname: He
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, P. R. China.
authors.forename: Chunsun
authors.initials: C
authors.lastname: Dai
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D002945:Cisplatin / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008856:Microscopy, Fluorescence; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D020011:Protective Agents; D008687:Metformin; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D002945:Cisplatin