Carvedilol attenuates ischemia-reperfusion-induced oxidative renal 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 carvedilol (CVD), an antihypertensive drug in I/R-induced renal failure in rats. The protective effect of CVD 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. Carvedilol (2 mg/kg, i.p.) was administered twice, 30 min prior to ischemia and 12 h after the reperfusion period. At the end of the reperfusion period, rats were killed. Thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH) levels, 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 CVD 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 CVD exerts renoprotective effects probably by the radical scavenging and antioxidant activities.
Singh
Devinder
D
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh - 160 014, India. devindercpsingh@yahoo.co.uk
Chander
Vikas
V
Chopra
Kanwaljit
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D005978:Glutathione / Q000819:agonists; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000975:Antioxidants; D002227:Carbazoles; D011412:Propanolamines; D017382:Reactive Oxygen Species; D000077261:Carvedilol; D010088:Oxidoreductases; D005978:Glutathione