Attenuation of renal ischemia-reperfusion injury by trimetazidine: evidence of an in vivo antioxidant effect.
Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antiischemic agent trimetazidine in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping the unilateral renal artery for 45 min followed by 24 h of reperfusion. Trimetazidine (2.5 mg/kg i.p.) was administered 24 and 12 h prior to renal artery occlusion and the same dose was given intravenously 1 h before inducing ischemia. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance compared with sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. Trimetazidine markedly reduced elevated levels of TBARS and significantly attenuated renal dysfunction and morphological changes in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect and the therapeutic potential of trimetazidine, an anti-ischemic agent, in attenuating renal ischemia-reperfusion injury.
Kaur
H
H
Pharmacology division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Padi
S S V
SS
Chopra
K
K
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012078:Renal Artery Obstruction / Q000150:complications; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014292:Trimetazidine / Q000008:administration & dosage / Q000494:pharmacology*; D014508:Urea / Q000097:blood / Q000652:urine
D000975:Antioxidants; D008054:Lipid Peroxides; D014508:Urea; D003404:Creatinine; D014292:Trimetazidine