Peters J M, Duncan J R, Wiley L M, Keen C L
Department of Obstetrics and Gynecology, University of California, Davis 95616, USA.
Toxicology. 1995 May 5;99(1-2):11-8. doi: 10.1016/0300-483x(94)02989-8.
To test the hypothesis that the developmental toxicity of cadmium (Cd) is due in part to oxidative damage, embryos were cultured in medium containing 0.0, 1.0, 3.0, or 6.0 microM Cd with or without various antioxidants for 72 h. Ascorbate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and glutathione (GSH) were all effective at ameliorating 1.0 microM Cd-induced embryotoxicity. For embryos cultured in medium containing either 3.0 or 6.0 microM Cd, GSH was effective at ameliorating Cd toxicity while the other antioxidants tested were ineffective. Pretreating embryos with antioxidants for 24 h prior to exposing them to Cd and antioxidants did not significantly alter the previously observed improvement with the exception that pretreatment with GSH virtually eliminated Cd-induced embryotoxicity between 1.0 and 6.0 microM Cd. A 4-h exposure to GSH prior to culture in Cd markedly improved embryo development suggesting that GSH taken up during pretreatment can provide protection against Cd-induced embryotoxicity. This work supports the hypothesis that the developmental toxicity of Cd is in part due to oxidative damage that can be modulated by select antioxidants.
为了验证镉(Cd)的发育毒性部分归因于氧化损伤这一假说,将胚胎在含有0.0、1.0、3.0或6.0微摩尔Cd的培养基中培养72小时,培养基中添加或不添加各种抗氧化剂。抗坏血酸、丁基羟基茴香醚(BHA)、丁基羟基甲苯(BHT)和谷胱甘肽(GSH)均能有效改善1.0微摩尔Cd诱导的胚胎毒性。对于在含有3.0或6.0微摩尔Cd的培养基中培养的胚胎,GSH能有效改善Cd毒性,而测试的其他抗氧化剂则无效。在将胚胎暴露于Cd和抗氧化剂之前,先用抗氧化剂预处理24小时,除了用GSH预处理实际上消除了1.0至6.0微摩尔Cd之间Cd诱导的胚胎毒性外,并未显著改变先前观察到的改善情况。在Cd中培养之前,先将胚胎暴露于GSH 4小时,可显著改善胚胎发育,这表明预处理期间摄取的GSH可提供针对Cd诱导的胚胎毒性的保护。这项工作支持了Cd的发育毒性部分归因于可由特定抗氧化剂调节的氧化损伤这一假说。