Combined toxicity of ethanol and methylmercury in rat

Abstract

The hepatotoxic and nephrotoxic effects of methylmercury (CH 3Hg) and ethanol (EtOH) are well known; however, their interaction in vivo is not clearly understood. In order to investigate the combined effects of these 2 substances, 4 groups of male Wistar rats with an initial weight of approximately 190 g were treated for 7 weeks. Each group consisting of 8 rats was gavaged as follows: Group 1 with 5.0 ml/kg body weight of double distilled water, Group 2 with 5.0 ml/kg body weight of 25% EtOH, Group 3 with 2.5 mg/kg of CH 3Hg in water, and Group 4 with 2.5 mg/kg of CH 3Hg in 25% EtOH. At the termination of the experiment the mean body weights of the rats in Group 3 (372.5 ± 10.8 S.E.) and Group 4 (383.4 ± 13.4) were significantly lower than that of Group 1 (433.0 ± 7.8). Linear regression showed a positive feed conversion efficiency for Groups 1 and 2 (1.07 and 0.83, respectively), and a negative score for this parameter for Groups 3 and 4 (−1.43, −1.53). At necropsy, rat livers from Group 3 exhibited random multifocal tan spots. The relative liver weights were similar to those of controls. Semithin sections of liver revealed an increase in lipid droplets in Groups 2 and 3 compared to those in the other 2 groups while vacuolization was more striking in CH 3Hg treated rats (Groups 3 and 4). Severe hepatolysis and portal canal edema were noted in the groups of rats exposed to either EtOH alone or in combination with mercury. The relative weight of left kidney in Group 3 (0.70 ± 0.03) and Group 4 (0.51 ± 0.04) rats was significantly greater than of the control (0.39 ± 0.03). In gross appearance the kidney was pale and the urine production was significantly higher ( P<0.05) in Group 3 compared to that of Group 1. Group 4 rats had significantly more ( P <0.50) Hg in the kidney than Group 3; however, the inorganic percentages in both groups were similar. Morphological examination of the kidney proximal tubules from CH 3Hg treated rats (Groups 3 and 4) revealed an increase in lipid droplets, vacuoles, cell sloughing and tubular degeneration compared to Groups 1 and 2. These histological changes in the proximal tubules of Groups 4 rats indicate an additive effect of EtOH on the kidney pathology caused by CH 3Hg. This present study seems to suggest that ethanol in combination with mercury enhances the retention of mercury in the kidney and increases the nephrotoxicity while it has no effect on the neurotoxicity of mercury. EtOH and CH 3Hg combination (Group 4) showed increased fibroblast infiltration and fibrosis in the kidney cortex, and larger and more numerous dense bodies and swollen mitochondria in the tubular cells. However, these alterations of nephrotoxicity by EtOH require further study.