PROTECTION BY ALBUMIN AGAINST ISCHEMIA-INDUCED AND HYPOXIA-INDUCED HEPATIC-INJURY

In previous studies using isolated perfused rat livers, we have shown that reactive oxygen species are involved in hypoxic and ischaemic liv er damage. Since albumin was shown to possess strong antioxidant prope rties we now investigated the capacity of albumin to prevent ischaemic and hypoxic damage in isolated perfused rat livers. Both, partial isc haemia and hypoxia/reoxygenation, resulted in marked hepatic injury as evidenced by an increased release of hepatic enzymes (GPT, LDH), by a strong decline of bile flow and by a decrease in hepatic GSH levels. With partial ischaemia, hepatic ATP depletion and calcium accumulation were also observed. Bovine serum albumin, added to the perfusate at c oncentrations of 0.1 or 1%, provided nearly complete protection agains t both types of liver injury. The same level of protection was also af forded by sulfhydryl-blocked and fatty acid-free bovine albumin prepar ations and by human albumin. In conclusion, the protective effect of a lbumin in our models of oxidative liver injury is neither due to the t hiol moiety nor to the presence of oxidizable Fatty acids in the album in fraction. More likely, albumin provides protection by an unspecific binding of redox-active transition metal ions capable of catalyzing r eactions which yield hydroxyl or hydroxyl-like radicals. Besides, unsp ecific sacrifice reactions of albumin with highly reactive oxygen spec ies or other endogenous compounds may also be implicated.