Effects of ascorbic acid deficiency on the [formula omitted] biosynthesis of cyclooxgenase metabolites in guinea pig lungs

Abstract

Endogenous levels of ascorbic acid may play a role in regulating the biosynthesis of cyclooxygenase metabolites in lungs of male guinea pigs. The in vitro biosyntheses of prostaglandins, prostacyclin and thromboxane were examined using isolated microsomal membranes from control and ascorbic acid deficient guinea pigs, under conditions in which the substrate concentration ([ 3H]-arachidonic acid) was varied from 10–100μM. Maintenance of guinea pigs for two weeks on an ascorbic acid deficient diet did not alter lung/body weight ratios, nor protein content of the lungs. Lung microsomes from ascorbic acid deficient guinea pigs demonstrated a greater biosynthesis of total cyclooxygenase metabolites at low substrate concentrations. A significant increase in the PGF 2α synthesis was observed in the scorbutic microsomes at 20μM arachidonic acid. At higher substrate concentrations the production of PGF 2α was significantly reduced in ascorbic acid deficient animals. By contrast, biosynthesis of thromboxane or prostacyclin in treated animals was not significantly different from control microsomes. At a substrate concentration of l00μM, there was equivalent synthesis of total cyclooxygenase metabolites in control and vitamin C deficient animals. The changes in prostaglandin biosynthesis were not due to an interaction of ascorbic acid with glutathione levels in the lung. These results support the hypothesis that ascorbic acid may modulate cyclooxygenase activity in the lung in a substrate dependent nature.