PT  - JOURNAL ARTICLE
AU  - Amin A. Nanji
AU  - Kalle Jokelainen
AU  - George K. K. Lau
AU  - Amir Rahemtulla
AU  - George L. Tipoe
AU  - Rathnagiri Polavarapu
AU  - El-Nasir Lalani
TI  - Arginine Reverses Ethanol-Induced Inflammatory and Fibrotic Changes in Liver Despite Continued Ethanol Administration
DP  - 2001 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 832--839
VI  - 299
IP  - 3
4099  - http://jpet.aspetjournals.org/content/299/3/832.short
4100  - http://jpet.aspetjournals.org/content/299/3/832.full
SO  - J Pharmacol Exp Ther2001 Dec 01; 299
AB  - We investigated the potential of arginine to reverse pathological changes in alcohol-induced liver injury. Four groups (six rats/group) of male Wistar rats were fed a fish oil-ethanol diet for 6 (group 2) or 8 (group 1) weeks. Rats in group 3 were fed fish oil-ethanol for 6 weeks, after which they were administered arginine with fish oil-ethanol for an additional 2 weeks. Rats in group 4 were fed fish oil-dextrose for 8 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, cytochrome P4502E1 activity, nuclear factor-κB, and levels of messenger RNA for tumor necrosis factor-α, cyclooxygenase-2, and inducible nitric oxide synthase. Concentrations of endotoxin were measured in plasma. The most severe inflammation and fibrosis was detected in groups 1 and 2, as were the highest levels of endotoxin, lipid peroxidation, cytochrome P450 2E1 activity, activation of nuclear factor-κB, and mRNA levels for tumor necrosis factor-α, cyclooxygenase-2, and inducible nitric oxide synthase. Plasma nitric oxide was also increased as was nitrotyrosine in liver. After arginine was administered, there was marked improvement in the pathological changes accompanied by decreased levels of endotoxin, lipid peroxidation, activation of nuclear factor-κB, tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide, and nitrotyrosine staining. The therapeutic effects of arginine are probably secondary to increased levels of nitric oxide but other effects of arginine cannot be excluded. The American Society for Pharmacology and Experimental Therapeutics