Inhibition of human platelet phospholipase A/sub 2/ by mono(2-ethylhexyl)phthalate
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 A/sub 2/ (PLA/sub 2/), one of the enzymes important in the release of arachidonic acid from membrane phospholipids. PLA/sub 2/ was measured by the liberation of /sup 14/C-arachidonic acid from 1-stearoyl-2-(1-/sup 14/C)arachidonyl-L-3-phosphatidylcholine. MEHP inhibits PLA/sub 2/ activity noncompetitively in intact human platelets and lysates with a K/sub i/ of 3.7 x 10/sup -4/ M. DEHP does not inhibit PLA/sub 2/ in whole platelets. Inhibition of PLA/sub 2/ 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.
- Research Organization:
- Ottawa Center, Ontario (Canada)
- OSTI ID:
- 6218802
- Journal Information:
- Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 78; ISSN EVHPA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ARACHIDONIC ACID
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CARBON 14 COMPOUNDS
CARBOXYLESTERASES
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
ENZYMES
ESTERASES
HYDROLASES
INHIBITION
LABELLED COMPOUNDS
LIPASE
MATERIALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHTHALATES
RADIOASSAY