Oral supplementation of L-arginine prevents chronic cyclosporine nephrotoxicity in rats.
This study was performed to evaluate the effect of L-arginine (L-Arg) on the prevention of chronic cyclosporine (CsA) nephrotoxicity in rats. Rats pair-fed a low-salt diet (0.05%) were given CsA (15 mg/kg/day s.c.), CsA and L-Arg (L-Arg group, 1.25 g/l water), CsA and N-nitro-L-arginine methyl ester (L-NAME group, 70 mg/l water) or vehicle. After 28 days, the L-Arg group had a higher glomerular filtration rate compared to the CsA (0.42 +/- 0.05 vs. 0.31 +/- 0.06 ml/min/100 g, p < 0.05) and the L-NAME groups (vs. 0.19 +/- 0.04 ml/min/100 g, p < 0.05) and a significantly lower serum creatinine level compared to the CsA (0.70 +/- 0.06 vs. 0.92 +/- 0.12 mg/dl, p < 0.05) and the L-NAME groups (vs. 1.21 +/- 0.17 mg/dl, p < 0.05). The L-Arg group had less fibrosis, tubular injury (TI), and arteriolopathy than the CsA (fibrosis 0.39 +/- 0.14 vs. 0.74 +/- 0.15; TI 1.3 +/- 0.3 vs. 2.0 +/- 0.1; arteriolopathy 33 +/- 7 vs. 48 +/- 17, p < 0.05, respectively) and the L-NAME groups (fibrosis vs. 1.67 +/- 0.32, TI vs. 2.6 +/- 0.3, arteriolopathy vs. 63 +/- 10, p < 0.05, respectively). Plasma renin activity in the L-Arg group was less than in the CsA (18 +/- 2 vs. 23 +/- 3 ng Ang I/ml/h, p < 0.05) and the L-NAME groups (vs. 30 +/- 3 ng Ang I/ml/h, p < 0.05). Nitric oxide production in L-Arg group was higher than in the CsA (24.2 +/- 1.7 vs. 11.1 +/- 1.5 mumol/24 h, p < 0.05) and the L-NAME groups (vs. 8.4 +/- 1.0 mumol/24 h, p < 0.05). In conclusion, the nitric oxide pathway is associated with the pathogenesis of chronic CsA nephrotoxicity, and exogenous L-Arg supplementation is effective in reducing chronic CsA nephrotoxicity in rats.
Yang
C W
CW
Department of Internal Medicine, Catholic University Medical College, Seoul, Korea.
Kim
Y S
YS
Kim
J
J
Kim
Y O
YO
Min
S Y
SY
Choi
E J
EJ
Bang
B K
BK
D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008274:Magnesium / Q000097:blood / Q000652:urine; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009318:Natriuresis; D009569:Nitric Oxide / Q000378:metabolism / Q000652:urine; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D016572:Cyclosporine; D001120:Arginine; D003404:Creatinine; D019001:Nitric Oxide Synthase; D012083:Renin; D008274:Magnesium; D019331:NG-Nitroarginine Methyl Ester