A study of the effects of p,p'-DDE and other related chlorinated hydrocarbons on inhibition of platelet aggregation.
A series of chlorinated hydrocarbons of interest in environmental toxicology were investigated concerning their effects on human platelet aggregation. Most potent in inhibiting platelet aggregation were p,p'-DDE and Arochlor 1242. Aggregation induced by arachidonic acid (1 mM) was more sensitive to inhibition by p,p'-DDE than was aggregation induced by ADP (10 microM). The former was completely inhibited by p,p'-DDE at a concentration of 1 x 10(-4) M, whereas there was only a 31% inhibition of the latter. Addition of Ca2+ (1 mM) blocked the inhibitory effect of p,p'-DDE on aggregation induced by both arachidonic acid and ADP. Calmodulin (1 microgram/ml) blocked the inhibitory effect of p,p'-DDE on aggregation induced by arachidonic acid but not that induced by ADP. The calmodulin inhibitory drugs trifluoperazine and calmidazolium had no effect at all or only a weak effect (-14%), respectively, on platelet aggregation. Increasing the concentrations of p,p'-DDE and Arochlor 1242 caused a delay in the onset of aggregation induced by the addition of arachidonic acid. The synthesis of thromboxane B2 and other prostaglandins in platelet membranes was dose-dependently reduced by p,p'-DDE. The structurally closely related isomers o,p'-DDE and p,p'-DDT did not significantly inhibit arachidonic acid-induced platelet aggregation or thromboxane B2 synthesis. It is concluded that p,p'-DDE and Arochlor 1242 inhibited platelet aggregation by inhibiting platelet cyclooxygenase activity.
Lundholm
C E
CE
Department of Pharmacology, University of Linköping, Sweden.
Bartonek
M
M
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003634:DDT / Q000031:analogs & derivatives / Q000494:pharmacology; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology*; D003632:Dichlorodiphenyldichloroethane / Q000494:pharmacology; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D006843:Hydrocarbons, Chlorinated; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D003633:Dichlorodiphenyl Dichloroethylene; D000244:Adenosine Diphosphate; C000849:bis(p-chlorophenyl)acetic acid; D003634:DDT; D003632:Dichlorodiphenyldichloroethane