EFFECTS OF TROLOX-C AND SIN-1 ON ARACHIDONIC-ACID METABOLISM AND ON CYCLIC-GMP FORMATION IN LEUKOCYTES

The effects of Trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carbox ylic acid), a vitamin E analogue, (60-900 mu M) and SIN-1 (3-morpholin o sydnonimine), a nitric oxide donor, (30-3000 mu M) On arachidonic ac id metabolism and on cyclic GMP formation in calcium ionophore A23187 (calcimycin)-stimulated human polymorphonuclear leukocytes were invest igated. Trolox C elicited a dose dependent decrease in leukotriene B-4 levels and increase in prostaglandin E(2) levels but did not affect c yclic GMP levels. SIN-1 dose dependently inhibited leukotriene B-4 and stimulated prostaglandin E(2) and cyclic GMP formation. Dibutyryl cyc lic GMP did not affect the formation of leukotriene B-4 and prostaglan din E(2). Trolox C (180 beta M), which itself had no effect on cyclic GMP levels, enhanced the effect of SIN-1 (100 mu M) on cyclic GMP leve ls more than 5-fold. The effects of SIN-1 on arachidonic acid metaboli sm seem to be independent of cyclic GMP and are probably due to nitric oxide. In this experimental model both Trolox C and SIN-1 have simila r actions on the prostaglandin/leukotriene ratio, and Trolox C potenti ates the SIN-1-induced increase in cyclic GMP levels.