title: Carvedilol protects against apoptotic cell death induced by cisplatin in renal tubular epithelial cells.
abstract: Cisplatin is a highly effective chemotherapeutic drug; however, its use is limited by nephrotoxicity. Studies showed that the renal injury produced by cisplatin involves oxidative stress and cell death mediated by apoptosis and necrosis in proximal tubular cells. The use of antioxidants to decrease cisplatin-induced renal cell death was suggested as a potential therapeutic measure. In this study the possible protective effects of carvedilol, a beta blocker with antioxidant activity, was examined against cisplatin-induced apoptosis in HK-2 human kidney proximal tubular cells. The mitochondrial events involved in this protection were also investigated. Four groups were used: controls (C), cisplatin alone at 25 μM (CIS), cisplatin 25 μM plus carvedilol 50 μM (CV + CIS), and carvedilol alone 50 μM (CV). Cell viability, apoptosis, caspase-9, and caspase-3 were determined. Data demonstrated that carvedilol effectively increased cell viability and minimized caspase activation and apoptosis in HK-2 cells, indicating this may be a promising drug to reduce nephrotoxicity induced by cisplatin.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Ribeirão Preto, SP, Brasil.
authors.forename: M A
authors.initials: MA
authors.lastname: Carvalho Rodrigues
authors.forename: G
authors.initials: G
authors.lastname: Gobe
authors.forename: N A G
authors.initials: NA
authors.lastname: Santos
authors.forename: A C
authors.initials: AC
authors.lastname: Santos
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002945:Cisplatin / Q000633:toxicity*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology*; D011412:Propanolamines / Q000494:pharmacology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000970:Antineoplastic Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D053148:Caspase 3; D053453:Caspase 9; D002945:Cisplatin