Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanol-induced liver injury

AIM: To study the expression and activity of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in rats with ethanol-induced liver injury and their relation with liver damage, activation of nuclear factor-kappa B (NF-kappa B) and tumor necrosis factor-alpha (TNF-alpha) expression in the liver. METHODS: Female Sprague-Dawley rats were given fish oil (0.5 mL) along with ethanol or isocaloric dextrose daily via gastrogavage for 4 or 6 wk. Liver injury was assessed using serum alanine aminotransferase (ALT) activity and pathological analysis. Liver malonclialdehyde (MDA), nitric oxide contents, NOS and eNOS activity were determined. NF-kappa B p65, NOS, eNOS and TNF-alpha protein or mRNA expression in the liver were detected by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Chronic ethanol gavage for 4 wk caused steatosis, inflammation and necrosis in the liver, and elevated serum ALT activity. Prolonged ethanol administration (6 wk) enhanced the liver damage. These responses were accompanied with increased lipid peroxidation, NO contents, NOS activity and reduced eNOS activity. NF-kappa B p65, NOS and TNF-alpha protein or mRNA expression were markedly induced after chronic ethanol gavage, whereas eNOS mRNA expression remained unchanged. The enhanced NOS activity and expression were positively correlated with the liver damage, especially the necro-inflammation, activation of NF-kappa B, and TNF-alpha mRNA expression. CONCLUSION: NOS expression and, activity are induced in the liver after chronic ethanol exposure in rats, which are correlated with the liver damage, especially the necro-inflammation, activation of NF-kappa B and TNF-alpha expression. eNOS activity is reduced, but its mRNA,expression is not affected. (c) 2006 The WIG Press. All rights reserved.