Effect of glucocorticoid on prostaglandin production during simulated shock conditions in the perfused cat liver

Abstract

The production of prostaglandins E 2 and F 2α by isolated perfused cat livers was quantitated during separate simulated shock conditions (i.e. ischemia, acidosis and hypoxia). Control livers showed little change in perfusate prostaglandin concentrations over a 150-min perfusion period. Neither ischemia nor acidosis produced significant increases in prostaglandin concentrations in the perfusate after 150 min of perfusion. Hypoxia resulted in a 4.5-fold increase in PGE 2 and a 3.5-fold increase in PGF 2α concentrations during this same period. Lactic acid dehydrogenase and cathepsin D activities were also elevated in the perfusate during hypoxia. Addition of methylprednisolone (10 −3 M) to the perfusate significantly retarded the release of PGE 2, PGF 2α, and cathepsin D into the perfusate during severe hypoxia, without significantly altering the increase in lactic acid dehydrogenase activity. The action of methylprednisolone on prostaglandin and lysosomal enzyme release in hypoxic livers may be the result of a membrane-stabilizing action of the glucocorticoid. One proposed mechanism for the inhibition by glucocorticoids of the increased prostaglandin production during hypoxia is that endogenous arachidonic acid is stabilized within the cell membrane phospholipids. Thus, less substrate is available for utilization by the prostaglandin synthetase system.