title: Effect of mercuric chloride intoxication and dimercaprol treatment on delta-aminolevulinate dehydratase from brain, liver and kidney of adult mice.
abstract: Dimercaprol is a compound used in the treatment of mercury intoxication, however with low therapeutic efficacy. It is assumed that dimercaprol acts by reactivating target sulfhydryl-containing proteins. In the present investigation we studied the inhibitory effect of mercuric chloride treatment (3 days with 2.3 or 4.6 mg/kg HgCl2, sc) in mice on cerebral, renal and hepatic delta-aminolevulinate dehydratase (ALA-D) activity, and a possible reversal of the effect of mercury by dimercaprol (0.25 mmol/kg, 24 hr after the last mercury injection). Mercuric chloride did not inhibit cerebral ALA-D at the doses injected. Dimercaprol treatment did not restore the normal enzyme activity of the liver after the 25% inhibition caused by 4.6 mg/kg HgCl2. In the kidney, dimercaprol enhanced the inhibitory effect of 4.6 mg/kg mercuric chloride (from 35% after mercury treatment alone to 65% after mercury plus dimercaprol treatment). Mercury content increased in kidney after exposure to 2.3 or 4.6 mg/kg and the levels attained were higher than in any other organ Mercury accumulated in liver only after exposure to 4.6 mg/kg HgCl2, and dimercaprol further increased mercury deposition. Dimercaprol treatment also increased the levels of mercury in brain of animals exposed to 4.6 mg/kg HgCl2 The enzymes from all sources presented similar sensitivity to the combined effect of HgCl2 and dimercaprol in vitro. In the absence of preincubation, 0-500 muM dimercaprol potentiated the inhibitory effect of HgCl2 on ALA-D activity. In the presence of preincubation, and 100 and 250 muM dimercaprol enhanced ALA-D sensitivity to mercury, whereas 500 muM dimercaprol partially protected the enzyme from mercury inhibition. Dimercaprol (500 muM) inhibited renal and hepatic ALA-D when preincubated with the enzymes. These data suggested that the dimercaprol-Hg complex may have a more toxic effect on ALA-D activity than Hg2+. Furthermore, the present data show that dimercaprol did not acts by reactivating mercury-inhibited sulfhydryl-containing ALA-D, and that indeed it may have an inhibitory effect per se depending on the tissue.
authors.affiliation: Department of Chemistry, Santa Maria Federal University, RS, Brasil.
authors.forename: T
authors.initials: T
authors.lastname: Emanuelli
authors.forename: J B
authors.initials: JB
authors.lastname: Rocha
authors.forename: M E
authors.initials: ME
authors.lastname: Pereira
authors.forename: L O
authors.initials: LO
authors.lastname: Porciuncula
authors.forename: V M
authors.initials: VM
authors.lastname: Morsch
authors.forename: A F
authors.initials: AF
authors.lastname: Martins
authors.forename: D O
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004112:Dimercaprol / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D008628:Mercury / Q000378:metabolism*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D000623:Porphobilinogen Synthase / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000931:Antidotes; D004112:Dimercaprol; D008627:Mercuric Chloride; D000623:Porphobilinogen Synthase; D008628:Mercury