Splenectomy attenuates superoxide anion release into the hepatic sinusoidsafter lipopolysaccharide challenge

Background/Aims: The aim of this study was to determine whether the spleen contributes to superoxide anion release into the hepatic sinusoids and subs equent damage to endothelial cells of the hepatic sinusoids after lipopolys accharide challenge. Methods: Rats were given 2 mg/kg body weight lipopolysaccharide, Three hour s after the treatment, superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome C method. Dama ge to endothelial cells of the hepatic sinusoids was assessed from the puri ne nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in the live r perfusate, To further characterize the mechanisms behind these changes, t hese studies were done in rats given superoxide dismutase or an anti-TNF al pha antibody. To study whether the spleen plays a role in the mechanisms, e xperiments with splenectomized rats were performed. Results: Lipopolysaccharide challenge resulted in superoxide anion release into the hepatic sinusoids and damage to endothelial cells of the hepatic s inusoids, These changes were significantly attenuated by the treatments wit h superoxide dismutase or an antibody against TNF alpha, as well as by sple nectomy, The hepatic macrophage and Kupffer cell populations after lipopoly saccharide challenge were significantly smaller in the rats given splenecto my than in those given a sham operation. There were no significant differen ces in the neutrophil populations between the two groups, Levels of TNF alp ha were significantly lower in the former than the latter, whereas there we re no significant differences in levels of Interleukin-8 between the two gr oups. Conclusions: Splenectomy reduced the superoxide anion release into the hepa tic sinusoids caused by the lipopolysaccharide challenge and subsequent dam age to endothelial cells of the hepatic sinusoids, This supports the view t hat splenectomy has a protective effect in lipopolysaccharide-induced liver injury.