Hormonal contraceptive increases plasma lipid peroxides in female rats. Relationship to platelet aggregation and lipid biosynthesis.

Abstract

We investigated whether changes in plasma oxidative properties could occur after oral (hormonal) contraceptive (OC) administration in female rats and whether such changes could be responsible for the platelet increase in aggregation and lipid biosynthesis observed with that treatment. Platelets and plasma (platelet-poor) from control and OC (ethinyl estradiol + lynestrenol)-treated rats were prepared separately. Thrombin-induced aggregation of control platelets was markedly enhanced after incubation for 4 (p less than 0.025) to 60 (p less than 0.001) minutes in OC as compared with control plasma. Under the same conditions, platelet lipid biosynthesis was increased also (p less than 0.05 to p less than 0.01), but after 3 hours incubation. The enhanced response of platelets to aggregation induced by OC plasma could be inhibited by adding either glutathione (p less than 0.025), vitamin E (p less than 0.025), catalase (p less than 0.05), or peroxidase + glutathione (p less than 0.005) to plasma or 2,6,di-bis(ter-butyl)p-cresol (p less than 0.05) to platelets before incubation. The peroxidized free fatty acids isolated from OC plasma added to normal platelets induced a 150% (p less than 0.001) increase in the response to thrombin as compared with the fatty acids from control plasma. In addition, the level of malondialdehyde and conjugated dienes was significantly (p less than 0.02 to p less than 0.001) increased in OC compared with control plasma. We conclude that the enhanced formation in plasma of lipid hydroperoxides seems to be the initial event stimulating platelets after OC treatment, at least in rats.