Carvedilol prevents the apoptosis of renal tubular cells in cisplatin-induced ARF

Objective To study the apoptosis of renal tubular cells in acute renal failure induced by cisplatin and the effect of carvedilol on such apoptosis. Methods Male wistar rats were randomly divided into four groups: group 1 received 0.85% saline 1 ml/200 g ip. single dose; group 2 received cisplatin 10 mg/kg ip; group 3 received carvedilol 15 rag/kg qd ig; group 4 received carvedilol 15 mg/kg qd ig. for 6 days, and cisplatin 10 mg/kg ip at day 4. Nephrotoxicity was assessed by measuring BUN, Scr, urinary acetylglucosaminidase(NAG) and histopathology of kidney 3 days after the cisplatin treatment. Tubular cell apoptosis was examined by TUNEL and DNA agarose gel electrophoresis. Protein expression of caspase-3 as well as malondialdehyde (MDA) content and superoxided dismutase (SOD) activity were detected in kidneys. Results Cisplatin induced a significant elevation in Scr, BUN, urinary NAG, renal tubular cell apoptosis, expression of caspase-3 as well as MDA content and severe morphology changes, while decreased the renal SOD activity. However, carvedilol improved above status of nephrotoxicity. Conclusions Renal tubular cell apoptosis is one of the important causes of cisplatin-induced ARF. Pretreatment with carvedilol can protect the rats from cisplatin-induced nephrotoxicity by reducing ROS, decreasing the apoptosis of renal tubulan cells, and partly inhibiting the caspase-dependent way.