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 1 day after reperfusion. Pre-ischemic treatment with L-carnosine dose-dependently (1, 10 microg/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-carnosine at a dose of 10 microg/kg significantly depressed the elevated norepinephrine level. On the other hand, although the higher dose of L-carnosine 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-carnosine 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-carnosine on ischemic acute renal failure is probably through the suppression of enhanced renal sympathetic nerve activity induced by ischemia/reperfusion.
Fujii
Toshihide
T
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, 569-1094 Osaka, Japan.
Takaoka
Masanori
M
Muraoka
Tomoko
T
Kurata
Hayato
H
Tsuruoka
Nobuo
N
Ono
Hiroyuki
H
Kiso
Yoshinobu
Y
Tanaka
Takaharu
T
Matsumura
Yasuo
Y
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002336:Carnosine / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D002336:Carnosine; D009638:Norepinephrine