Cadmium and glutathione: effect on human placental thromboxane and prostacyclin production

Cadmium toxicity, noted in rodents during late gestation, has been compared with preeclampsia, a condition associated with an imbalance between thromboxane A2 and prostacyclin. This study examines the effect of cadmium on the human placental production of thromboxane A2 and prostacyclin, as reflected by their hydrolysis products (TxB2, 6-keto-PGF1 alpha). Following two 12-h exposures, 6-keto-PGF1 alpha production by placental explants was 74.8 and 39.9% of unexposed tissue values at 40 and 100 microM cadmium, respectively, with no significant effect on TxB2. The effect of glutathione on placental TxB2 and 6-keto-PGF1 alpha production was also examined. Sulfhydryl concentrations have been shown to affect thromboxane and prostacyclin production, and glutathione binds to cadmium reducing its toxicity. Although glutathione at concentrations up to 1 mM had no effect on explant function, glutathione did prevent the effects of cadmium on 6-keto-PGF1 alpha. This study indicates that acute exposure to cadmium at high concentrations directly affects the placental production of 6-keto-PGF1 alpha, disturbing the thromboxane A2/prostacyclin ratio.