title: Cd modifies hepatic Zn deposition and modulates δ-ALA-D activity and MT levels by distinct mechanisms.
abstract: Cadmium (Cd) is a pollutant that is harmful to human and animals. The liver is a target for Cd accumulation and it can disrupt Zn homeostasis. Here we examined the interaction of Zn and Cd to determine how these two metals could affect δ-aminolevulinate-dehydratase (δ-ALA-D) and metallothionein (MT), two potential molecular endpoints for Cd hepatotoxicity. Cd exposure (0.25 and 1 mg kg1 body weight, i.p., for 10 days) caused a marked increase in hepatic Zn deposition, which was not modified by treatment with Zn (2 mg kg1 , i.p.). Cd caused a dose-dependent increase in hepatic Cd content that was not modified by Zn. Zn and/or Cd treatment increased hepatic δ-ALA-D activity, although the increase caused by Cd was less marked. Reactivation index of δ-ALA-D by DTT was decreased by Zn and Cd exposure, which indicates that Zn protects enzyme from oxidation. Hepatic MT was increased only after exposure to 1 mg kg(-1) Cd and Zn reduced the stimulation of MT synthesis. The results presented here indicate that Cd can redistribute Zn from non-hepatic tissues to liver and the increase in hepatic Zn deposition can account for the increase in hepatic δ-ALA-D activity after Cd exposure. However, Zn blocked the increase in hepatic MT levels caused by Cd. Thus, the modulation of the two molecular endpoints of Cd toxicity used here was distinct, which indicates that the mechanism(s) involved in Zn and Cd distribution, δ-ALA-D and MT regulation are not coincident.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Marcos Martins
authors.initials: MM
authors.lastname: Braga
authors.forename: Tuiskon
authors.initials: T
authors.lastname: Dick
authors.forename: Diogo Losch
authors.initials: DL
authors.lastname: de Oliveira
authors.forename: Adriele Scopel
authors.initials: AS
authors.lastname: Guerra
authors.forename: Marina Concli
authors.initials: MC
authors.lastname: Leite
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ardais
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D000623:Porphobilinogen Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D004785:Environmental Pollutants; D002104:Cadmium; D008668:Metallothionein; D000623:Porphobilinogen Synthase; D015032:Zinc