Nitric oxide as an independent regulatory factor in regenerating rat liver

Nitric oxide production and lipid peroxidation modulate the proliferating activity of liver cells, but the relationship between enhanced nitric oxide production, lipid peroxidation, and liver regeneration remains unclear. We examined the role of nitric oxide and lipid peroxidation on experimental liver regeneration. Thirty-five male Wistar albino rats underwent a sham operation (I), partial hepatectomy alone (II, IV), partial hepatectomy and daily N-nitro-L-arginine methyl ester (L-NAME) treatment for 24-hrs (III) or 48-hrs (V). Liver tissue concentrations of catalase, nitrite and nitrate, glutathione, and serum levels of alaninaminotransferase and bilirubin were measured. CD34, Ki-67 and proliferating cell nuclear antigen were evaluated in liver samples. Compared with other groups, both of the L-NAME groups had decreased tissue nitric oxide concentrations. Nitrate and nitrite (nitric oxide) concentrations were higher in partial hepatectomy-alone groups, as were CD34 counts and proliferation indexes. Partial hepatectomy elevated catalase, and glutathione levels in all groups compared to the sham-operated controls. In conclusion, nitric oxide inhibition impaired hepatic regeneration following partial hepatectomy. An obvious effect of nitric oxide on lipid peroxidation in the context of hepatocyte and endothelial cell proliferation could not be demonstrated. Thus, while lipid peroxidation could influence some steps in liver regeneration, nitric oxide poses as an independent regulatory factor in regenerating rat liver.