Insulin-like growth factor-I ameliorates transient ischemia-induced acute renal failure in rats.
Acute renal failure in rats was induced by transient occlusion of bilateral renal arteries and veins to investigate whether insulin-like growth factor-I (IGF-I) has an effect on the damaged renal function or not. Administration of IGF-I at 0.01, 0.1 and 1 mg/kg by s.c. injection caused a 18.7, 33.0 and 66.5% increase of glomerular filtration rate and 54.8, 61.2 and 84.1% decrease of blood urea nitrogen, respectively, compared with the values in the saline-treated group 2 days after ischemia. Other renal parameters tested such as fractional excretion of sodium, N-acetyl-beta-D-glucosaminidase and tubular reabsorptance of phosphorus which are thought to represent renal function of proximal and distal tubules, respectively, were also improved by IGF-I treatment. A histochemical study also supported these observations. Severe epithelial necrosis of proximal tubules and decrease of brush borders were observed 2 days after transient ischemia in the saline-treated group, whereas marked histochemical alterations were not observed in the IGF-I-treated group. L-NG-nitroarginine, an inhibitor of nitric oxide synthetase, prevented the improvement of glomerular filtration rate and blood urea nitrogen by IGF-I at 1 mg/kg, suggesting that the ameliorative action on renal function by IGF-I is mediated via nitric oxide, possibly its vasodilating action. These findings provide the first evidence for the efficacy of IGF-I in the model of acute renal failure, suggesting that IGF-I may be useful for the treatment of acute renal failure.
Noguchi
S
S
Preclinical Research Department, CIBA-GEIGY Japan, Limited, Hyogo.
Kashihara
Y
Y
Ikegami
Y
Y
Morimoto
K
K
Miyamoto
M
M
Nakao
K
K
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D004357:Drug Synergism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000502:physiology; D012082:Renal Veins / Q000502:physiology
D019335:Nitroarginine; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D001120:Arginine