The effect of selenium compounds (selenite, selenate, ebselen) on the production of thromboxane and prostacyclin by the human term placenta in vitro.
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 F1 alpha (6-keto-PGF1 alpha), the inactive hydrolysis products of TxA2 and PGI2. Although selenate exposure (40 microM 24 hr) increased TxB2 production, and ebselen (an organic selenium compound with GPX activity) exposure (40 microM, 24 hr) decreased both TxB2 and 6-keto-PGF1 alpha production, only selenite had a significant effect on the TxB2/6-keto-PGF1 alpha ratio. Three exposures to selenite at 6 microM (32 hr) significantly decreased 6-keto-PGF1 alpha production with no effect on TxB2 production or tissue GPX activity. Following two exposures to selenite at 20 and 40 microM (24 hr), TxB2 production was significantly increased, while tissue 6-keto-PGF1 alpha 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-PGF1 alpha ratio, which may be related to increased vasoconstriction and blood coagulation.
D001393:Azoles / Q000494:pharmacology; D015415:Biomarkers; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis*; D005979:Glutathione Peroxidase / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D054833:Isoindoles; D007773:Lactates / Q000096:biosynthesis; D016566:Organoselenium Compounds / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D064586:Selenic Acid; D018036:Selenium Compounds / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*
D001393:Azoles; D015415:Biomarkers; D006063:Chorionic Gonadotropin; D054833:Isoindoles; D007773:Lactates; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; C042986:ebselen; D013929:Thromboxane B2; D011464:Epoprostenol; D005979:Glutathione Peroxidase; D018038:Sodium Selenite; D064586:Selenic Acid