Effect of trimetazidine on renal ischemia/reperfusion injury in rats.
There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of trimetazidine, in I/R induced renal failure in rats. The protective effect of trimetazidine (Tmz) against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague-Dawley rats using histopathological and biochemical parameters. In one set of experiments animals were unilaterally nephrectomized, and subjected to 45 min of left renal pedicle occlusion and in another set both the renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Trimetazidine (3 mg kg(-1), i.p.) was administered 30 min prior to ischemia and repeated 12 h after the first dose. At the end of the reperfusion period, rats were sacrificed. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, glutathione reductase (GR) catalase (CAT), and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with trimetazidine markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes. The findings imply that ROS play a causal role in I/R induced renal injury and trimetazidine exert renoprotective effects probably by the radical scavenging and antioxidant activities.
Singh
Devinder
D
Pharmacology Division, University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh 160014, India.
Chopra
Kanwaljit
K
D000818:Animals; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D014292:Trimetazidine / Q000494:pharmacology / Q000627:therapeutic use*
D014292:Trimetazidine