Effects of glutathione depletion on selenite- and selenate-induced embryotoxicity in cultured rat embryos.
Effects of depletion of reduced glutathione (GSH) on selenium (Se) embryotoxicity in cultured rat embryos were examined. Rat embryos at day 9.5 of gestation were cultured for 48 h in the presence of Se as either sodium selenite at 10 and 20 microM or sodium selenate at 30 and 100 microM. Embryonic GSH was depleted by the addition of 0.1 mM of L-buthionine-[S,R]-sulfoximine (BSO) without embryotoxicity, i.e., significant growth retardation and malformation of the embryos. Selenite at 10 microM or selenate at 100 microM significantly increased the incidence of malformation of the embryos. The incidence of selenite-induced malformation of the embryos at 20 microM was significantly decreased with BSO. On the contrary, the incidence of selenate-induced malformation at 30 microM was significantly increased with BSO. It was noted that the major malformed regions of the embryos by the embryotoxic concentration of BSO alone were the same to those affected by selenite or selenate. It was considered from these results that embryonic GSH was involved in the embryotoxicity of selenite and selenate. The embryotoxicity of selenate may not be mediated through the reduction to selenite. It was suggested that the formation of selenodiglutathione and the oxidative stress were involved in the embryotoxicity of selenite and selenate, respectively.
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan. usami@nihs.go.jp
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D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D005865:Gestational Age; D005978:Glutathione / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D064586:Selenic Acid; D018036:Selenium Compounds / Q000633:toxicity*; D018038:Sodium Selenite / Q000633:toxicity*
D018036:Selenium Compounds; D019328:Buthionine Sulfoximine; D005978:Glutathione; D018038:Sodium Selenite; D064586:Selenic Acid