Effects of methylmercury exposure during the second stage of rapid postnatal brain growth on negative geotaxis and on delta-aminolevulinate dehydratase of suckling rats.
In the present study, we examined the effects of exposure to methylmercury (0, 2.3, 4.6, 6.9 and 9.2 mg/kg, daily for 5 consecutive days, sc) during the second stage of rapid postnatal brain development (8 to 12 days of age) on the sulfhydryl-containing enzyme delta-aminolevulinate dehydratase (ALA-D, E.C. 4.2.1.24) from brain, liver and kidney and on motor performance (latency to complete a negative geotaxis response) of rats. ALA-D specific activity of 13-day old rats of both sexes (7-12 per group) was reduced significantly in rats treated with 6.9 mg/kg and 9.2 mg/kg in brain (about 40%, P < 0.05) and in liver (about 25%, P < 0.05). Renal ALA-D specific activity was not affected by methylmercury treatment. The in vitro IC50 for inhibition of brain, liver and renal ALA-D was 79.3, 81.8 and 39.1 microM, respectively. The latency to complete the negative geotaxis response of 12-day old rats was increased by 6.9 (7.9 +/- 0.7 s, mean +/- SEM) and 9.2 mg/kg methylmercury (7.8 +/- 0.5 s) when compared with control rats (5.8 +/- 0.3 s), suggesting an impairment in motor performance of exposed rats. These results demonstrate that exposure to relatively high doses of methylmercury during the second stage of brain development causes a significant reduction in brain and hepatic ALA-D. The absence of inhibition of ALA-D by lower doses may be related to the relatively low in vitro sensitivity of the enzyme to methylmercury. The possible involvement of ALA-D inhibition on the neurotoxicity of methylmercury deserves additional investigation.
Rocha
J B
JB
Departamento de Química, Universidade Federal de Santa Maria, RS, Brasil.
Freitas
A J
AJ
Marques
M B
MB
Pereira
M E
ME
Emanuelli
T
T
Souza
D O
DO
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight; D001921:Brain / Q000201:enzymology / Q000254:growth & development*; D005260:Female; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000506:poisoning*; D000623:Porphobilinogen Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D008767:Methylmercury Compounds; D000623:Porphobilinogen Synthase