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 adminis tration of CCl4. CCl4 was administered three times a week for 8 weeks to male Wistar rats treated simultaneously with N-omega-nitro-L-argini ne 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., tw ice a day); appropriate controls were performed. Serum NO2- + NO3- inc reased in the groups treated with CCl4 and/or L-arginine, but the effe ct was prevented by either L-NAME or AG. In the liver, lipid peroxidat ion and collagen content increased, while glycogen content decreased i n the CCl4-treated group (P < 0.05); L-NAME and AG accentuated these e ffects. Serum enzyme activities of alanine aminotransferase (ALT), alk aline phosphatase, and gamma-glutamyl transpeptidase (gamma-GTP) and b ilirubin 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 prote cted the liver partially from the elevation of collagen, bilirubins, a nd alkaline phosphatase and from glycogen depletion induced by CCl4 in toxication (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 st udied herein. (C) 1998 Elsevier Science Inc.