Cell Biol Toxicol 2006; 22: 429–438. DOI: 10.1007/s10565-006-0119-8 C  Springer 2006 Antioxidants and metallothionein levels in mercury-treated mice R. Brand˜ ao 1 , F.W. Santos 1 , M. Farina 1,2 , G. Zeni 1 , D. Bohrer 1 , J.B.T. Rocha 1 and C.W. Nogueira 1 1 Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; 2 Departamento de Bioqu´ ımica, Centro de Ciˆ encias Biol ´ ogicas, Universidade Federal de Catarina, Florian´ opolis, SC, Brazil Received 2 May 2006; accepted 11 July 2006; Published online 11 September 2006 Keywords: mercuric chloride, metallothionein, selenium, 2,3-dimercapto-1-propanesulfonic acid, N- acetylcysteine Abstract Acute effects of mercury on mouse blood, kidneys, and liver were evaluated. Mice received a single dose of mercuric chloride (HgCl 2 , 4.6mg/kg, subcutaneously) for three consecutive days. We investigated the possible beneficial effects of antioxidant therapy (N-acetylcysteine (NAC) and diphenyl diselenide (PhSe) 2 ) compared with the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), an effective chelating agent in HgCl 2 exposure in mice. We also verified whether metallothionein (MT) induction might be involved in a possible mechanism of protection against HgCl 2 poisoning and whether different treatments would modify MT levels and other toxicological parameters. The results demonstrated that HgCl 2 exposure significantly inhibited δ-aminolevulinate dehydratase (δ-ALA-D) activity in liver and only DMPS treatment prevented the inhibitory effect. Mercuric chloride caused an increase in renal non- protein thiol groups (NPSH) and none of the treatments modified renal NPSH levels. Urea concentration was increased after HgCl 2 exposure. NAC plus (PhSe) 2 was partially effective in protecting against the ef- fects of mercury. DMPS and (PhSe) 2 were effective in restoring the increment in urea concentration caused by mercury. Thiobarbituric acid-reactive substances (TBARS), aspartate aminotransferase (AST), and ala- nine aminotransferase (ALT) activities and ascorbic acid levels were not modified after mercury exposure. Mercuric chloride poisoning caused an increase in hepatic and renal MT levels and antioxidant treatments did not modify this parameter. Our data indicated a lack of therapeutic effect of the antioxidants tested. Abbreviations: δ-ALA-D, δ-aminolevulinate dehydratase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; DMPS, Sodium salt of 2,3-dimercapto-1-propanesulfonic acid; DMSO, dimethyl sul- foxide; GC, gas chromatography; GR, glutathione reductase; GSH, glutathione; HPLC, high-performance liquid chromatography; MDA, malondialdehyde; MT, metallothionein; NAC, N-acetylcysteine; NPSH, non-protein thiol groups; RBC, red blood cells; ROS, reactive oxygen species; SH, sulfhydryl; TBARS, thiobarbituric acid-reactive substances Introduction Mercury is widely used in industry, medicine, agriculture, and other fields (ATSDR, 1989). Mercury is a transition metal; it promotes the formation of reactive oxygen species (ROS) such as hydrogen peroxides (Hussain et al., 1999). Accordingly, mercury exposure has been