Attenuation of glycerol-induced acute renal failure in rats by trimetazidine and deferoxamine.
The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves, among other causes, ischaemia, vascular congestion, and reactive oxygen metabolites. The aim of this study was to investigate the roles of ischaemia and iron-induced oxidative stress by employing trimetazidine, an anti-ischemic drug with an additional antioxidant effect, and deferoxamine, an iron chelator, in glycerol-induced acute renal failure in rats. Five groups of rats were employed in this study: group 1 served as control group, group 2 was given 50% glycerol alone (8 ml/kg i.m.), group 3 was given glycerol plus trimetazidine (3 mg/kg), and groups 4 and 5 were given glycerol plus deferoxamine (50 and 100 mg/kg, respectively). Renal injury was assessed by measuring plasma creatinine and blood urea nitrogen levels and creatinine and urea clearances. The oxidative stress was measured on the basis of the renal malondialdehyde and reduced glutathione levels and the activities of catalase, glutathione reductase, and superoxide dismutase. Glycerol treatment resulted in marked renal oxidative stress and deranged renal functions which significantly improved by trimetazidine and deferoxamine treatments. Deferoxamine, by interacting with Fenton reaction chemistry, and trimetazidine, by its anti-ischaemic and antioxidative properties, protected the kidney against the oxidative stress and the resultant renal dysfunction produced by glycerol. Based on these results, this study points towards renal ischaemia and iron as potential mediators and demonstrates the potential beneficial effects of deferoxamine and trimetazidine in glycerol-induced acute renal failure in rats.
Chander
Vikas
V
Division of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Singh
Devinder
D
Chopra
Kanwaljit
K
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005990:Glycerol; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D007502:Iron Chelating Agents; D014665:Vasodilator Agents; D003676:Deferoxamine; D014292:Trimetazidine; D005990:Glycerol