Pentavalent antimonial drugs such as
meglumine antimoniate (
Glucantime [Glu; Sanofi-Aventis, São Paulo, Brazil]) produce severe side effects, including
cardiotoxicity and hepatotoxicity, during the treatment of
leishmaniasis. We evaluated the role of residual Sb(III) in the hepatotoxicity of
meglumine antimoniate, as well as the protective effect of the
antioxidant ascorbic acid (AA) during antimonial
chemotherapy in a murine model of
visceral leishmaniasis. BALB/c mice infected with Leishmania infantum were treated intraperitoneally at 80 mg of Sb/kg/day with commercial
meglumine antimoniate (Glu) or a synthetic
meglumine antimoniate with lower Sb(III) level (MA), in association or not with AA (15 mg/kg/day), for a 20-day period. Control groups received saline or saline plus AA. Livers were evaluated for hepatocytes histological alterations,
peroxidase activity, and apoptosis. Increased proportions of swollen and apoptotic hepatocytes were observed in animals treated with Glu compared to animals treated with saline or MA. The
peroxidase activity was also enhanced in the liver of animals that received Glu. Cotreatment with AA reduced the extent of histological changes, the apoptotic index, and the
peroxidase activity to levels corresponding to the control group. Moreover, the association with AA did not affect the hepatic uptake of Sb and the ability of Glu to reduce the liver and spleen parasite loads in infected mice. In conclusion, our data supports the use of pentavalent antimonials with low residue of Sb(III) and the association of pentavalent antimonials with AA, as effective strategies to reduce side effects in antimonial
therapy.