EFFECT OF FE-OVERLOAD ON THE BIOTRANSFORMATION OF METHYLMERCURY IN RAT

It is well documented that methylmercury (MeHg) in vivo slowly undergo es demethylation reaction to change to inorganic mercury (Hg-i). The c leavage of the C-Hg bond was suggested to occur via a reactive oxygen- mediated process in vitro. To study the possibility of the involvement of hydroxyl radical (.OH) in the demethylation of MeHg in vivo, the c ombined effect of Fe-overload and carbon tetrachloride (CCl4) treatmen t on the rate of biotransformation of MeHg was examined in rats. The e ffects of this treatment on H2O2-scavenging enzyme activities (catalas e and glutathione peroxidase) were also studied. Rats were fed 3.5% Fe (II) fumalate-containing diet for 0, 7 or 21 d to load Fe. Feeding of the Fe-containing diet brought about a time-dependent increase of the hepatic Fe levels by nearly 7-fold after 3 weeks. The serum Fe levels showed a maximum on day 7, while the renal levels increased after day 7. TBA-reactive substance levels in the liver significantly increased along with the Fe feeding, and this increase was drastically accelera ted by CCl4 treatment, suggesting the effective production of .OH. The CCl4-induced stimulation of the lipid peroxidation was observed also in serum and kidney, though not as marked as in the liver. The hepatic accumulations of total and inorganic Hg at 72 h after MeHg administra tion were significantly increased by the Fe-feeding. The proportion of Hg-i to total Hg in this tissue increased markedly by the combined ef fect of Fe and CCl4 with the concomitant decrease of catalase activity . On the other hand, the renal accumulation of Hg-i drastically decrea sed by the Fe-load, while the MeHg levels remained unchanged. Since th e renal metallothionein levels were found to be lowered after the Fe-f eeding, this might account for the reduced retention of Hg-i in the wh ole kidney. The present results suggest that reactive oxygen species, probably .OH, induced by Fe and CCl4 treatment may play a critical rol e in the biotransformation of MeHg in the liver.