Sex Difference in Acute Renal Dysfunction Induced by Methylmercury in Mice

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Abstract
To investigate the sex-related difference of susceptibility of renal function to methylmercury (MeHg) toxicity, various doses of MeHg chloride (MMC, 20–200 μmol/kg) were orally administered to C57BL/6N mice of both sexes. On days 1, 3, 5, and 7 after MMC administration, the extent of damage to renal junction and the renal Hg levels were examined. After dosing, female mice survived much longer than males. With the increase in the dose level to 200 μmol/kg, the changes of the renal Hg levels 24 h after administration showed biphasic features with a plateau of around 85 μg/g. The renal Hg in male mice increased more rapidly to the plateau than in females. The doses by which the renal Hg level reached the plateau were 80 and 120 μmol/kgfor males and females, respectively. The time-dependent decrease of the renal Hg became much slower with dose levels exceeding 80 and 160 μmol/kg for males and females, respectively. Inhibition of phenolsulfonphthalein excretion and increase of plasma creatinine after the MMC administration were more marked in males than in females. Inorganic Hg levels in the kidney of MeHg-intoxicated mice were much lower than that of HgCl2-intoxicated mice, indicating that the involvement of inorganic Hg, a product of biotransformation of MeHg, in the renal failure caused by MMC treatment would be negligible. Although pathological changes in the renal proximal tubules of HgCl2-intoxicated mice were marked, those of the MeHg-intoxicated group were slight. The results obtained here suggest that the kidney is one of the primary target organs in MeHg acute toxicity, and that the kidney of male mice has a higher susceptibility to MeHg toxicity than that of females.