Effect of treatment with mercury chloride and lead acetate during the second stage of rapid postnatal brain growth on delta-aminolevulinic acid dehydratase (ALA-D) activity in brain, liver, kidney and blood of suckling rats.
The sensitivity of developing rodents to toxic metals differs considerably from that of adults. In the present study, we investigated the in vivo and in vitro effects of inorganic mercury and lead on delta-aminolevulinic acid dehydratase (ALA-D) from brain, liver, kidney and blood of young rats. Eight day-old rats were injected with one or five doses of lead acetate (0, 3.5, or 7.0 mg/kg) or HgCl2 (0, 2.5, or 5.0 mg/kg). In vitro, the IC50 for mercury inhibition of cerebral, renal and hepatic ALA-D was in the 124 to 160 microM range, while values for lead acetate was in the 7 to 12 microM range. The IC50 of blood enzyme for lead (0.8 microM) and mercury (6.5 microM) was significantly lower than that observed for the other tissues. A single dose of lead did not affect the enzyme activity, but a single dose of HgCl2 (5 mg/kg) caused a significant inhibition of ALA-D from kidney (40%, P < 0.01) and liver (25%, P < 0.05). Five doses of lead acetate (3.5 or 7 mg/kg) caused an inhibition of about 25 and 40%, respectively (P < 0.01), of hepatic ALA-D, and an increase of 1.4-fold (P < 0.05) and 2.6-fold (P < 0.01) of blood enzyme, respectively. Treatment with five doses of HgCl2 (5 mg/kg) caused an inhibition of about 25, 60, 50, and 80% of ALA-D from brain, blood, liver and kidney, respectively (all P < 0.05). Five doses of 2.5 mg/kg HgCl2 caused an inhibition of ALA-D from liver (40%, P < 0.01) and kidney (45%, P < 0.01). These results demonstrate that ALA-D from young rat tissues show different sensitivities to mercury and lead. The enzyme was more affected by mercury than by lead in vivo, while in vitro lead was more potent that mercury as an ALA-D inhibitor.
Rocha
J B
JB
Departamento de Quimica, Universidade Federal de Santa Maria, RS, Brasil.
Pereira
M E
ME
Emanuelli
T
T
Christofari
R S
RS
Souza
D O
DO
D000704:Analysis of Variance; D000818:Animals; D000833:Animals, Suckling; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001798:Blood Proteins; D009942:Organometallic Compounds; D007854:Lead; D008627:Mercuric Chloride; D000623:Porphobilinogen Synthase; C008261:lead acetate