The Effect of Selenium Compounds (Selenite, Selenate, Ebselen) on the Production of Thromboxane and Prostacyclin by the Human Term Placenta in Vitro

Abstract

Selenium not only has an important role in controlling lipid hydroperoxides through glutathione peroxidase (GPX) activity, but also can produce oxidative stress through exposure to selenite. Because levels of lipid hydroperoxides affect the production of thromboxane A2 (TxA2) and prostacyclin (PGI2), selenium compounds may be able to influence the production of these two vasoactive substances. Late-gestation pregnancy reduces the half-life of PGI2; therefore, pregnancy itself may enhance susceptibility to changes in the production of TxA2 and PGI2. The objective of this investigation was to determine if different selenium compounds, selenite, selenate, and ebselen, can influence the human term placental production of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α), the inactive hydrolysis products of TxA2 and PGI2. Although selenate exposure (40 μM 24 hr) increased TxB2 production, and ebselen (an organic selenium compound with GPX activity) exposure (40 μM, 24 hr) decreased both TxB2 and 6-keto-PGF1α production, only selenite had a significant effect on the TxB2/6-keto-PGF1α, ratio. Three exposures to selenite at 6 μM (32 hr) significantly decreased 6-keto-PGF1α production with no effect on TxB2 production or tissue GPX activity. Following two exposures to selenite at 20 and 40 μM (24 hr), TxB2 production was significantly increased, while tissue 6-keto-PGF1α production and tissue GPX activity were significantly decreased. These results indicate that selenite, but not selenate or ebselen, can directly affect the human placenta by producing changes in the TxB2/6-keto-PGF1α ratio, which may be related to increased vasoconstriction and blood coagulation.