DIFFERENTIAL-EFFECTS OF EXOGENOUS AND ENDOGENOUSLY GENERATED H2O2 ON PHAGOCYTIC-ACTIVITY AND GLUCOSE-RELEASE OF NORMAL AND CIRRHOTIC LIVERS

Background/Aims: Reactive oxygen species play an essential role in nec ro-inflammatory processes. Therefore, the aim of the present studies w as to investigate the effect of exogenous and endogenously produced H2 O2 on the phagocytic capacity and glucose release of perfused cirrhoti c rat livers in comparison with that on the controls. Methods: Complet e septal cirrhosis was achieved by oral treatment of rats with thioace tamide for 6 months. The phagocytic capacity of the perfused livers wa s measured by the uptake of colloidal carbon. During the continuous pe rfusion with colloidal carbon, either H2O2 or benzylamine was added to the perfusion medium for a limited time period. The latter functioned as an endogenous H2O2 donor. Results: In control rats exogenous and e ndogenously produced H2O2 caused a transient stimulation of the hepati c colloidal carbon uptake as web as of the glucose release. Inhibition of the catalase by aminotriazol doubled the changes evoked by H2O2, w hereas blockade of the Kupffer cells by GdCl3 drastically reduced its stimulatory effect. Cirrhotic livers took up less colloidal carbon and released lower amounts of glucose than the controls when stimulated b y exogenous H2O2. The inhibition of the nitric oxide synthetase augmen ted the H2O2-induced effect in controls as well as in the cirrhotic li vers by 250% and 620% (colloidal carbon uptake) and 340% and 760% (glu cose release), respectively. The blockade of the eicosanoid production by indomethacin and caffeic acid drastically increased the glucose re lease and the colloidal carbon uptake in controls and, in absolute ter ms, to a lesser extent in cirrhotic livers. Endogenous H2O2 produced b y the addition of benzylamine stimulated the colloidal carbon uptake a nd glucose release in livers from both groups. The inhibition of the l ipoxygenase increased both parameters, whereas different effects were elicited by the addition of superoxide dismutase in controls and cirrh otic livers. Conclusion: The maximum uptake of colloidal carbon and gl ucose release, measured after stimulation by H2O2, was lower in cirrho tic livers than in controls, thus indicating a lowered phagocytic capa city of Kupffer cells and altered glycogenolytic response of the hepat ocytes in cirrhotic livers. The use of various effecters provided evid ence that superoxide anions, nitric oxide and, possibly, arachidonic a cid are involved in the signal transduction between Kupffer cells and hepatocytes when stimulated by exogenous or endogenously produced H2O2 . This signalling mechanism seems to be impaired in cirrhotic livers.