Stacey N H
Toxicology. 1986 Dec 1;42(1):85-93. doi: 10.1016/0300-483x(86)90095-8.
Although various theories have been proposed to account for the mechanism of cadmium-induced cellular injury, none have received strong, direct support from experimental data. An interference with sulfhydryl groups is one of the proposed mechanisms. The ability of reduced glutathione (GSH) to protect hepatocytes from the toxic effects of cadmium has been investigated. When added just prior to cadmium, GSH has a pronounced protective effect, while an additional 15 min after cadmium resulted in partial protection against the ensuing loss of cellular potassium ion. The protection against loss of aspartate aminotransferase into the medium is pronounced, regardless of whether addition of GSH is at zero time or 15 min after cadmium. Addition of the GSH at either time resulted in reduced levels of cadmium associated with the hepatocytes, and may well account for these protective properties of GSH. Protein-bound sulfhydryl groups showed a small decrease in response to cadmium but only after cell injury had been initiated. These data allow the conclusion that cadmium does not exert its cytotoxic effects by simple, single irreversible interaction with cellular thiol groups. Furthermore, as the added GSH remains extracellular, these data indicate that protection can be afforded at an extracellular level even after intracellular exposure to toxic concentrations of cadmium.
尽管已经提出了各种理论来解释镉诱导细胞损伤的机制，但没有一种理论得到实验数据的有力直接支持。干扰巯基是提出的机制之一。已经研究了还原型谷胱甘肽（GSH）保护肝细胞免受镉毒性作用的能力。在镉之前立即添加时，GSH具有明显的保护作用，而在镉添加后额外15分钟添加则对随后的细胞钾离子损失起到部分保护作用。无论GSH是在零时间添加还是在镉添加后15分钟添加，对天冬氨酸转氨酶释放到培养基中的保护作用都很明显。在这两个时间点添加GSH都会导致与肝细胞相关的镉水平降低，这很可能解释了GSH的这些保护特性。蛋白质结合的巯基对镉的反应仅在细胞损伤开始后略有下降。这些数据可以得出结论，镉不会通过与细胞硫醇基团简单、单一的不可逆相互作用来发挥其细胞毒性作用。此外，由于添加的GSH仍留在细胞外，这些数据表明即使在细胞内暴露于有毒浓度的镉之后，在细胞外水平也可以提供保护。
