Protection of hypoxic cytotoxicity by glucocorticoid in the liver

Abstract

Induction of hypoxia for 2.5 h in perfused cat livers resulted in a 10-fold increase in cathepsin D and a 15-fold increase in lactic dehydrogenase (LDH) activities in the perfusate and a 42% depression of the clearance rate of particles by the reticuloendothelial system (RES). Addition of 10⁻³ M methylprednisolone (MP) to the perfusate only slightly retarded the release of LDH, but significantly (P<0.05) inhibited cathepsin D release by 90% at 150 min. Liver flow did not change during the perfusion period when MP was added to control or hypoxic livers. Similarly, MP did not significantly alter oxygen consumption in perfused livers. However, MP protected against the reduction in carbon clearance during hypoxia without inducing blockade of colloidal carbon clearance. Moreover, opsonization of carbon with autologous plasma did not improve the clearance of colloidal carbon above that observed in nonopsonized experiments. Thus, pharmacologic doses of a synthetic glucocorticoid protected RES cells and release of lysosomal hydrolases during severe hypoxia in isolated perfused cat livers probably by stabilization of cellular and intracellular (lysosomal) membranes.