Poznan University of Medical Sciences, Department of Toxicology, Poland.
Poznan University of Medical Sciences, Department of Toxicology, Poland.
Environ Toxicol Pharmacol. 2017 Dec;56:290-296. doi: 10.1016/j.etap.2017.10.004. Epub 2017 Oct 10.
Toxic effects of ethylene glycol (EG) and its metabolites are mainly related to metabolic acidosis and kidney damage. EG biotransformation involving CYP2E1 affects the oxidant-antioxidant balance. The study assessed the effect of repeated administration of 4-methylpyrazole (4MP, 15mg/kg b.w. after 2h, followed by 10mg/kg b.w. every 12h) on renal function (creatinine, urea and urinary protein levels) as well as products of kidney's lipid peroxidation (MDA and TBARS levels) in rats poisoned with EG (5745mg/kg b.w.). Serum EG and glycolic acid (GA) concentrations were measured throughout the experiment. Repeated administration of 4MP reduced the rate of EG elimination, extended the period of EG persistence in serum and significantly limited formation of GA. The study showed the temporary intensification of kidney oxidative processes that correlated with changes in kidney function. It was found that the use of 4MP in EG poisoning inhibited its biotransformation to toxic metabolites, but simultaneously intensified oxidative damages in kidneys.
乙二醇（EG）及其代谢物的毒性作用主要与代谢性酸中毒和肾脏损伤有关。涉及 CYP2E1 的 EG 生物转化会影响氧化还原平衡。本研究评估了重复给予 4-甲基吡唑（4MP，2 小时后给予 15mg/kg bw，然后每 12 小时给予 10mg/kg bw）对 EG（5745mg/kg bw）中毒大鼠肾功能（肌酐、尿素和尿蛋白水平）以及肾脏脂质过氧化产物（MDA 和 TBARS 水平）的影响。在整个实验过程中测量了血清 EG 和乙醇酸（GA）的浓度。重复给予 4MP 可降低 EG 的消除率，延长其在血清中的持续时间，并显著限制 GA 的形成。该研究表明，肾氧化过程暂时加剧，与肾功能变化相关。结果发现，在 EG 中毒中使用 4MP 抑制了其向有毒代谢物的生物转化，但同时加剧了肾脏的氧化损伤。
