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Toxicology. 1992;72(1):17-26.

Influence of dietary protein levels on the fate of methylmercury and glutathione metabolism in mice.

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Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto, Japan.


We investigated the influence of dietary protein levels on the fate of methylmercury (MeHg), the tissue glutathione (GSH) levels and the efflux rates of GSH in C57BL/6N male mice. One group of mice was fed a 7.5% protein diet (low protein diet, LPD) and the other was fed a 24.8% protein diet (normal protein diet, NPD). The cumulative amount of Hg in urine in LPD-fed mice was approximately 3.7-times lower than in NPD group during the 7 days after oral administration of MeHg (20 mumol/kg), although the fecal Hg levels were identical in the two groups. Hg concentration in kidney, liver and blood decreased time-dependently for 7 days after the administration in both groups of mice, whereas the brain levels continued to increase during this period. Tissue Hg levels in the LPD group were significantly higher than in the NPD group except for the liver. Although the hepatic GSH level in LPD-fed mice was significantly lower than in NPD-fed mice, the levels in the kidney, brain, blood and plasma were not different between the two groups. The efflux rate (mumol/g body weight per day) of hepatic GSH in LPD-fed mice was significantly lower than in the NPD group, whereas the efflux rates of renal GSH were identical in both groups. When MeHg (20 mumol/kg)-pretreated mice were injected with acivicin, a specific inhibitor of gamma-glutamyltranspeptidase, the urinary Hg levels increased by 60- and 36-fold in groups fed LPD and NPD, respectively. As a result, the difference in urinary Hg levels between the two groups disappeared with acivicin treatment. This result indicated that LPD feeding might decrease urinary Hg excretion by increasing the retention of MeHg metabolite(s) in renal cells. Thus, our present study suggested that the dietary protein status, which could modulate the metabolism of thiol compounds, played an important role in determining the fate of MeHg.

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