Nitric oxide protection of rat liver from lipid peroxidation, collagen accumulation, and liver damage induced by carbon tetrachloride.
The aim of this work was to determine if the inhibition or stimulation of NO synthesis modulates liver damage induced by the chronic administration of CCl4. CCl4 was administered three times a week for 8 weeks to male Wistar rats treated simultaneously with N omega-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg, p.o., twice a day), aminoguanidine (AG, 4 g/L in the drinking water), or L-arginine (500 mg/kg, p.o., twice a day); appropriate controls were performed. Serum NO2- + NO3- increased in the groups treated with CCl4 and/or L-arginine, but the effect was prevented by either L-NAME or AG. In the liver, lipid peroxidation and collagen content increased, while glycogen content decreased in the CCl4-treated group (P < 0.05); L-NAME and AG accentuated these effects. Serum enzyme activities of alanine aminotransferase (ALT), alkaline phosphatase, and gamma-glutamyl transpeptidase (gamma-GTP) and bilirubin content increased about 2-, 3-, 2-, and 6-fold, respectively, after CCl4 intoxication (P < 0.05); L-NAME or AG cotreatment further increased the enzyme activities (P < 0.05). L-Arginine treatment protected the liver partially from the elevation of collagen, bilirubins, and alkaline phosphatase and from glycogen depletion induced by CCl4 intoxication (P < 0.05), but showed no significant effect on ALT, gamma-GTP, or lipid peroxidation. These results suggest that NO protects the liver against oxidative injury, because NO inhibition by L-NAME or AG increased lipid peroxidation and the other markers of liver injury studied herein.
Muriel
P
P
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N., México, DF, México. pmuriel@mail.cinvestav.mx
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D003094:Collagen / Q000378:metabolism*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D006146:Guanidines; D008112:Liver Glycogen; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D003094:Collagen; D001120:Arginine; D002251:Carbon Tetrachloride; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester