title: Effect of metformin against cisplatin induced acute renal injury in rats: a biochemical and histoarchitectural evaluation.
abstract: Although cisplatin has been a mainstay for cancer therapy, its use is limited mainly because of nephrotoxicity. Accumulating literature suggest the antioxidant and cytoprotective effect of metformin, a first line antidiabetic drug. With this background, we investigated the effect of metformin on the cisplatin induced nephrotoxicity in rats. A single injection of cisplatin (7.5 mg/kg, i.p.) caused marked renal damage, characterized by a significant increase in blood urea nitrogen (BUN), serum creatinine (Cr) and abnormal histo-architecture of kidney. These were accompanied by significant elevation of malondialdehyde (MDA), total reactive oxygen species (tROS) and caspase-3 levels and decreased antioxidant levels. Metformin treatment significantly attenuated the increase in malondialdehyde and tROS generation and restores the decrease in both enzymatic and non-enzymatic antioxidants. However metformin treatment did not prevent the cisplatin induced renal injury as there was no significant difference of renal function parameters (BUN and Cr), kidney histopathology as well as caspase-3 activity between cisplatin per se and metformin plus cisplatin treated rats. Histopathology studies revealed that similar glomerular and tubular pathological architecture in both cisplatin per se and cisplatin plus metformin group. In conclusion, the present study demonstrated that metformin is not an adjuvant drug to treat nephrotoxicity associated with cisplatin therapy.
authors: Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors: Bidya Dhar
authors: BD
authors: Sahu
authors: Madhusudana
authors: M
authors: Kuncha
authors: Uday Kumar
authors: UK
authors: Putcha
authors: Ramakrishna
authors: R
authors: Sistla
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D008687:Metformin; D005978:Glutathione; D001205:Ascorbic Acid; D002945:Cisplatin
keywords: Apoptosis; Cisplatin; Metformin; Nephrotoxicity; Oxidative stress