Inhibition of Microcystin-Induced Release of Cyclooxygenase Products from Rat Hepatocytes by Anti-Inflammatory Steroids

Abstract

Abstract

We showed previously that exposure to microcystin causes eicosanoid release. That study was extended further to test the effect of glucocorticoids on microcystin-induced release of [¹⁴C]arachidonic acid and its metabolites from rat hepatocytes previously treated with [¹⁴C]arachidonic acid. Release of total radioactivity was 4-fold greater from hepatocytes after 2-hr incubation with 1 μM microcystin than after incubation with control medium. Fluocinolone pretreatment decreased the microcystin-induced synthesis and release of prostacyclin by 24 ± 2.6% (P < 0.05) and thromboxane B² by 39 ± 3% (P < 0.025). Treatment of hepatocyte cultures with either microcystin (1 μM) or steroids had no effect on cell viability or total cell protein. Total radioactivity released into the incubation medium was not affected by glucocorticoid alone. Under these conditions, the quantities of both prostaglandin F₂ α and prostaglandin E₂ released were not significantly different when control and microcystin-treated cultures were compared. The half-maximal inhibition (IC₅₀) values obtained from the dose-response data for the inhibition of arachidonic acid release by steroids were comparable with normal Cortisol levels in humans. Dose-response curves gave the following rank order of inhibitory potency: fluocinolone > dexamethasone > hydrocortisone. These results suggest that glucocorticoid therapy might be beneficial in microcystin toxicosis.