Girardi G, Elías M M
Facultad de Ciencias, Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, República Argentina.
Toxicology. 1993 Jul 11;81(1):57-67. doi: 10.1016/0300-483x(93)90156-m.
Mercury renal disposition has been studied following HgCl2 injection (5.0 mg/kg body wt., s.c.) in controls, diethylmaleate and N-acetylcysteine-treated rats. The different treatments were used to generate statistically different degrees of non-protein sulfhydryls concentration in kidneys. Diethylmaleate (4 mmol/kg body wt., i.p.) diminished kidney glutathione levels to 25% and N-acetylcysteine (2 mmol/kg body wt., i.p.) increased kidney non-protein sulfhydryls levels up to 75% compared with new controls. The amount of mercury in the kidneys, the mercury excretion rate in urine and the mercury plasma disappearance curves were calculated during 3 h post HgCl2 injection. BUN was measured in plasma at the same time period to determine the onset of kidney damage. The results indicate a higher HgCl2 renal clearance in N-acetylcysteine-treated rats compared to controls and less renal mercury accumulation. The data agree with diminished renal toxicity. On the other hand, renal mercury accumulation was higher and mercury renal clearance lower in diethylmaleate-treated animals, associated with higher renal toxicity. The results suggest that non-protein sulfhydryl levels (principally glutathione) might determine renal accumulation of mercury as well as its elimination rate and hence might enhance or mitigate the nephrotoxicity induced by the metal.
在对照组、经马来酸二乙酯和N-乙酰半胱氨酸处理的大鼠中,通过皮下注射氯化汞(5.0毫克/千克体重)来研究汞在肾脏中的分布情况。采用不同的处理方法,以在肾脏中产生统计学上不同程度的非蛋白巯基浓度。与新的对照组相比,马来酸二乙酯(4毫摩尔/千克体重,腹腔注射)使肾脏谷胱甘肽水平降至25%,而N-乙酰半胱氨酸(2毫摩尔/千克体重,腹腔注射)使肾脏非蛋白巯基水平提高至75%。在注射氯化汞后的3小时内,计算肾脏中的汞含量、尿汞排泄率和汞在血浆中的消失曲线。在同一时间段内测定血浆中的尿素氮,以确定肾脏损伤的起始情况。结果表明,与对照组相比,N-乙酰半胱氨酸处理的大鼠对氯化汞的肾脏清除率更高,肾脏汞蓄积更少。这些数据与肾脏毒性降低相符。另一方面,马来酸二乙酯处理的动物肾脏汞蓄积更高,肾脏汞清除率更低,伴有更高的肾脏毒性。结果表明,非蛋白巯基水平(主要是谷胱甘肽)可能决定汞在肾脏中的蓄积及其清除率,因此可能增强或减轻该金属诱导的肾毒性。