Labow R S, Meek E, Adams G A, Rock G
Ottawa Centre, Canadian Red Cross, Blood Transfusion Service, Ontario, Canada.
Environ Health Perspect. 1988 Jun;78:179-83. doi: 10.1289/ehp.8878179.
There is evidence that the carcinogenic and teratogenic effects attributed to the plasticizer di(2-ethylhexyl)phthalate (DEHP) are due to its major metabolite mono(2-ethylhexyl)phthalate (MEHP). MEHP is also formed ex vivo by a plasma enzyme in blood products stored in polyvinyl chloride (PVC) DEHP plastic containers. People who receive large amounts of blood products, such as hemophiliacs or patients undergoing hemodialysis, cardiopulmonary bypass, or massive transfusion, are exposed to significant levels of plasticizer. In this study, the platelet was used to show that MEHP inhibits phospholipase A2 (PLA2), one of enzymes important in the release of arachidonic acid from membrane phospholipids. Arachidonate is the parent molecule for the synthesis of prostaglandins, thromboxanes, leukotrienes, and lipoxins that are made by a wide variety of cells. PLA2 was measured by the liberation of 14C-arachidonic acid from 1-stearoyl-2-[1-14C]arachidonyl-L-3-phosphatidylcholine. MEHP inhibits PLA2 activity noncompetitively in intact human platelets and lysates with a Ki of 3.7 x 10(-4) M. DEHP does not inhibit PLA2 in whole platelets. Inhibition of PLA2 by MEHP occurs at only three times the circulating level of MEHP measured in neonates undergoing exchange transfusion and 20-fold the levels experienced by patients during cardiopulmonary bypass. Therefore, infants and adult patients with multisystem failure who accumulate MEHP in their blood may be at risk for decreased platelet function.
有证据表明，增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）的致癌和致畸作用是由其主要代谢产物单（2-乙基己基）邻苯二甲酸酯（MEHP）所致。MEHP也可在体外由储存在聚氯乙烯（PVC）DEHP塑料容器中的血液制品中的血浆酶形成。接受大量血液制品的人，如血友病患者或接受血液透析、体外循环或大量输血的患者，会接触到大量的增塑剂。在本研究中，使用血小板来表明MEHP抑制磷脂酶A2（PLA2），这是一种在从膜磷脂中释放花生四烯酸过程中起重要作用的酶。花生四烯酸盐是由多种细胞合成前列腺素、血栓素、白三烯和脂氧素的母体分子。通过从1-硬脂酰-2-[1-14C]花生四烯酰-L-3-磷脂酰胆碱中释放14C-花生四烯酸来测量PLA2。MEHP在完整的人血小板和裂解物中以非竞争性方式抑制PLA2活性，其Ki为3.7×10（-4）M。DEHP在全血中不抑制PLA2。MEHP对PLA2的抑制作用仅在接受换血治疗的新生儿中测得的MEHP循环水平的三倍以及体外循环期间患者所经历水平的20倍时出现。因此，血液中积累MEHP的婴儿和多系统功能衰竭的成年患者可能存在血小板功能下降的风险。
