Monochloramine potently inhibits arachidonic acid metabolism in rat platelets

Abstract

In the present study, the effects of hypochlorous acid (HOCl), monochloramine (NH 2Cl), glutamine-chloramine (Glu-Cl) and taurine-chloramine (Tau-Cl) on the formation of 12-lipoxygenase (LOX) metabolite, 12-HETE, and cyclooxygenase (COX) metabolites, TXB 2, and 12-HHT, from exogenous arachidonic acid (AA) in rat platelets were examined. Rat platelets (4 × 10 8/ml) were preincubated with drugs for 5 min at 37 °C prior to the incubation with AA (40 μM) for 2 min at 37 °C. HOCl (50–250 μM) showed an inhibition on the formation of LOX metabolite (12-HETE, 5–67% inhibition) and COX metabolites (TXB 2, 33–73% inhibition; 12-HHT, 27–74% inhibition). Although Tau-Cl and Glu-Cl up to 100 μM were without effect on the formation of 12-HETE, TXB 2 and 12-HTT, NH 2Cl showed a strong inhibition on the formation of all three metabolites (10–100 μM NH 2Cl, 12-HETE, 21–92% inhibition; TXB 2, 58–94% inhibition; 12-HHT, 36–92% inhibition). Methionine reversed a reduction of formation of LOX and COX metabolites induced by NH 2Cl, and taurine restoring that induced by both NH 2Cl and HOCl. These results suggest that NH 2Cl is a more potent inhibitor of COX and LOX pathways in platelets than HOCl, and taurine and methionine can be modulators of NH 2Cl-induced alterations in the COX and LOX pathways in vivo.