Preventive effect Of L-carnosine on ischemia/reperfusion-induced acute renal failure in rats

We investigated the effect of L-carnosine (beta-alanyl-L-histidine) on ischemic acute renal failure in rats. Ischemic acute renal failure was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in untreated acute renal failure rats markedly decreased at I day after reperfusion. Pre-ischemic treatment with L-camosine dose-dependently (1, 10 mug/kg, i.v.) attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of untreated acute renal failure rats revealed severe renal damage, which was significantly suppressed by pre-treatment With L-carnosine, at each dose given. In untreated acute renal failure rats, norepinephrine concentrations in renal venous plasma remarkably increased within 2 min after reperfusion and thereafter rapidly decreased. Pre-ischemic treatment With L-camosine at a dose of 10 mug/kg significantly depressed the elevated norepinephrine level. On the other hand, although the higher dose of L-camosine given 5 min after reperfusion tended to ameliorate the renal dysfunction after reperfusion, the improvement was moderate compared with those seen in pre-ischemic treatment. These results indicate that L-camosine prevents the development of ischemia/reperfusion-induced renal injury, and the effect is accompanied by suppression of the enhanced norepinephrine release in the kidney immediately after reperfusion. Thus, the preventing effect Of L-camosine on ischemic acute renal failure is probably through the suppression of enhanced renal sympathetic nerve activity induced by ischemia/reperfusion. (C) 2003 Elsevier B.V. All rights reserved.