Tanaka-Kagawa T, Suzuki M, Naganuma A, Yamanaka N, Imura N
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108, Japan.
J Pharmacol Exp Ther. 1998 Apr;285(1):335-41.
Inorganic mercury has a high affinity for the kidneys and causes acute renal failure. The present investigation was designed to determine the cause of the strain difference in sensitivity of mice to the renal toxicity of inorganic mercury. Renal damage caused by HgCl2 was estimated by histopathological and biochemical assessment, such as increase in blood urea nitrogen and plasma creatinine levels, and was found to be more remarkable in C3H/He than in C57BL/6 mice. Increase in renal lipid peroxidation in C3H/He was greater than that in C57BL/6 mice. However, no strain difference was observed in renal activities of glutathione (GSH) peroxidase, superoxide dismutase and GSH S-transferase in HgCl2-untreated mice. The GSH content and activities of catalase and GSSG reductase in kidney of HgCl2-untreated mice were higher in C3H/He than in C57BL/6. Background level of renal metallothionein content and the extent of metallothionein induction by HgCl2 showed no strain difference. On the other hand, renal mercury accumulation was higher and urinary mercury excretion was lower in C3H/He than in C57BL/6. The activity of renal gamma-glutamyltranspeptidase (gamma-GTP), which plays a key role in renal mercury accumulation, was higher in C3H/He than in C57BL/6. Furthermore, the increase in blood urea nitrogen by HgCl2, renal mercury accumulation and renal gamma-GTP activity in B6C3F1 mice were intermediate between those of the parent strains. These results suggest that the strain difference in renal toxicity of inorganic mercury seems to be caused by the discrepancy in renal mercury accumulation, and therefore, renal gamma-GTP may be an important factor determining the susceptibility of mice to the toxic action of inorganic mercury.
无机汞对肾脏具有高度亲和力，并可导致急性肾衰竭。本研究旨在确定小鼠对无机汞肾毒性敏感性的品系差异原因。通过组织病理学和生化评估（如血尿素氮和血浆肌酐水平升高）来估计氯化汞引起的肾损伤，结果发现C3H/He小鼠的肾损伤比C57BL/6小鼠更显著。C3H/He小鼠肾脂质过氧化的增加大于C57BL/6小鼠。然而，在未用氯化汞处理的小鼠中，谷胱甘肽（GSH）过氧化物酶、超氧化物歧化酶和GSH S-转移酶的肾脏活性未观察到品系差异。未用氯化汞处理的小鼠肾脏中，C3H/He小鼠的GSH含量以及过氧化氢酶和谷胱甘肽二硫化物还原酶的活性高于C57BL/6小鼠。肾脏金属硫蛋白含量的背景水平以及氯化汞诱导金属硫蛋白的程度未显示出品系差异。另一方面，C3H/He小鼠的肾脏汞蓄积量高于C57BL/6小鼠，而尿汞排泄量则较低。在肾脏汞蓄积中起关键作用的肾脏γ-谷氨酰转肽酶（γ-GTP）活性，C3H/He小鼠高于C57BL/6小鼠。此外，B6C3F1小鼠中氯化汞引起的血尿素氮增加、肾脏汞蓄积和肾脏γ-GTP活性介于亲本品系之间。这些结果表明，无机汞肾毒性的品系差异似乎是由肾脏汞蓄积的差异引起的，因此，肾脏γ-GTP可能是决定小鼠对无机汞毒性作用易感性的重要因素。
