Protective Effects of Vasodilatory Βeta-Blockers Carvedilol and Nebivolol against Glycerol Model of Rhabdomyolysis-Induced Acute Renal Failure in Rats

BACKGROUND Rhabdomyolysis (RM)-induced acute renal failure (ARF) accounts for about 10-40% of all cases of ARF. AIM The present study investigated the possible protective effect of two nitric oxides (NO)-releasing third generation β-blockers, carvedilol (Carv) and nebivolol (Nebi), against RM-mimicking glycerol (Gly)-induced ARF in rats. MATERIAL AND METHODS After 24 h dehydration, rats received a single dose of 50% Gly (8 ml/kg, im). They were treated with vehicle, Carv (2.5 mg/kg/day, po) or Nebi (10 mg/kg, po) for 3 successive days starting from an hour prior to Gly injection. Evaluation of blood pressure and locomotor activity was performed during the experiment. 72 h following Gly administration, total protein in the urine, serum levels of creatinine, blood urea nitrogen, sodium and potassium as well as the renal contents of malondialdehyde, reduced glutathione and NO were assessed, together with a histopathological examination of renal tissues. RESULTS Carv and Nebi attenuated Gly-induced renal dysfunction and histopathological alterations. They decreased the Gly-induced oxidative stress and increased renal NO concentration. Restoration of normal blood pressure and improvement of locomotor activity were also observed. CONCLUSION The results clearly demonstrate protective effects of Carv and Nebi against renal damage involved in RM-induced ARF and suggest a role of their antioxidant and NO-releasing properties.