Na K J, Jeong S Y, Lim C H
Korea Ginseng and Tobacco Research Institute, Taejon.
Arch Toxicol. 1992;66(9):646-51. doi: 10.1007/BF01981504.
Ascorbate treatment 30 min prior to sodium dichromate (20 or 30 mg/kg, s.c.) shows higher potency than that of glutathione (GSH) in protecting against both the metabolic disturbance and nephrotoxicity induced by dichromate. However, ascorbate treatment after 2 h of dichromate intoxication had no effect on dichromate-induced blood urea nitrogen (BUN) elevation 3 days after intoxication. In contrast, dichromate-induced glucosuria, which reached maximum levels at 3 days after treatment, was significantly decreased by GSH or N-acetyl cysteine (NAC) treatment, even if its administration was after 24 h of dichromate intoxication. Pretreatment with GSH depletors such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) had no effect on dichromate-induced nephrotoxicity. GSH levels in the liver and kidney were not affected at 3 h after dichromate treatment. However, dichromate significantly increased tissue GSH levels with a marked increase in liver per kidney GSH ratio at 24 h after treatment, if food was withheld subsequent to dichromate treatment, indicating that GSH biosynthesis resulted from the accelerated protein breakdown. These results suggest that GSH-mediated dichromate reduction is not a kinetically favorable pathway in vivo; however, GSH plays an important role in protection against dichromate-induced nephrotoxicity. In addition, the cellular metabolism of dichromate in the early period after treatment is important in the pathogenesis of its nephrotoxicity.
在重铬酸钠（20或30毫克/千克，皮下注射）给药前30分钟给予抗坏血酸治疗，在预防重铬酸盐引起的代谢紊乱和肾毒性方面，其效力高于谷胱甘肽（GSH）。然而，在重铬酸盐中毒2小时后给予抗坏血酸治疗，对中毒3天后重铬酸盐引起的血尿素氮（BUN）升高没有影响。相比之下，即使在重铬酸盐中毒24小时后给予GSH或N-乙酰半胱氨酸（NAC）治疗，重铬酸盐引起的糖尿（在治疗后3天达到最高水平）也会显著降低。用马来酸二乙酯（DEM）和丁硫氨酸亚砜胺（BSO）等GSH消耗剂进行预处理，对重铬酸盐引起的肾毒性没有影响。重铬酸盐治疗3小时后，肝脏和肾脏中的GSH水平未受影响。然而，如果在重铬酸盐治疗后禁食，治疗24小时后重铬酸盐会显著提高组织GSH水平，肝脏与肾脏的GSH比值也会显著增加，这表明GSH生物合成源于加速的蛋白质分解。这些结果表明，GSH介导的重铬酸盐还原在体内不是一个动力学上有利的途径；然而，GSH在预防重铬酸盐引起的肾毒性方面起着重要作用。此外，治疗后早期重铬酸盐的细胞代谢在其肾毒性的发病机制中很重要。
