CHRONIC EFFECTS OF METHYLMERCURY IN RATS .1. BIOCHEMICAL ASPECTS

To examine chronic effects of methylmercury (MeHg), male Wistar rats w ere fed on MeHg-contaminated diet, 0, 1 and 5 ppm Hg, under a restrict ed feeding schedule of 16 g/rat/day for 6 days a week. Rats were kille d at 6-month intervals for examination of Hg accumulation, tissue leve ls of glutathione, metallothionein and lipid peroxide, as well as anti -oxidative enzyme activities. The survival of the 5 ppm Hg group, 50% of which died by the end of 32nd month of the exposure, was somewhat s horter than control and 1 ppm Hg groups, 50% of which survived for 34 months. Although the rats showed no neurological signs or decreased bo dy weight gain even in 5 ppm Hg-exposed group until the end of the 2nd year, crossing of hind limb was evident after 2.5 years in all three groups. Accordingly, the neurological sign observed here possibly due to aging rather than MeHg toxicity. Tissue Hg levels showed a dose-dep endent accumulation except for the kidney, where the highest Hg accumu lation was observed among tissues examined. Renal Hg levels in the 1 p pm group showed about 40% of those in the 5 ppm group. Significant eff ects by MeHg mere evident only in the kidney, where glutathione and me tallothionein levels increased in both MeHg-exposed groups. However, l ipid peroxide levels elevated only in 1 ppm group. Among the antioxida tive enzymes examined, the renal glutathione peroxidase was found to b e the most labile enzyme against MeHg exposure. Renal dysfunction sugg ested by increased plasma creatinine levels was also significant in 5 ppm Hg rats at 2 years. Furthermore, anemia, which would be caused by reduced erythropoietin production in the kidney was also evident in th is group. The present study suggested that the kidney was the most sus ceptible organ against MeHg toxicity under the present exposure schedu le and that the renal dysfunction might at least partly account for th e shortened survival in 5 ppm Hg rats. (C) 1997 Tohoku University Medi cal Press.