Combined toxicity of ethanol and methylmercury in rat.
The hepatotoxic and nephrotoxic effects of methylmercury (CH3Hg) 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 CH3Hg in water, and Group 4 with 2.5 mg/kg of CH3Hg 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 CH3Hg 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 that of the control (0.39 +/- 0.03). In gross appearance the kidney was pale and the urine production was significantly higher (P less than 0.05) in Group 3 compared to that of Group 1. Group 4 rats had significantly more (P less than 0.05) Hg in the kidney than Group 3; however, the inorganic percentages in both groups were similar. Morphological examination of the kidney proximal tubules from CH3Hg 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 Group 4 rats indicate an additive effect of EtOH on the kidney pathology caused by CH3Hg.(ABSTRACT TRUNCATED AT 400 WORDS)
McNeil
S I
SI
Department of Biomedical Sciences, University of Guelph, Ontario, Canada.
Bhatnagar
M K
MK
Turner
C J
CJ
D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007672:Kidney Cortex / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008628:Mercury / Q000032:analysis; D008767:Methylmercury Compounds / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains
D008767:Methylmercury Compounds; D000431:Ethanol; D008628:Mercury