RESUMO
Mercury is known to interact with selenite and when the two are co-administered, one reduces the toxicity of the other. The main goal of this study was to investigate the simultaneous in vitro effects of sodium selenite (Se(4+)) and mercuric chloride (Hg(2+)) on the activity of hepatic, renal and cerebral delta-aminolevulinate dehydratase (delta-ALA-D) of adult male mice (Swiss albino). Hg(2+) inhibited delta-ALA-D from tissue supernatants and the IC(50) values for hepatic, renal and cerebral enzyme inhibition were 38+/-4.2, 67.5+/-4.3 and 46.2+/-3.7 microM, respectively. Se(4+) displayed a higher inhibitory action toward delta-ALA-D activity than Hg(2+). Simultaneous addition of Se(4+) and Hg(2+) to the delta-ALA-D assay increased the inhibition of the enzyme. Se(4+) and Hg(2+) oxidized total -SH groups from hepatic, renal and cerebral supernatants, although the effect of Se(4+) decreased in the presence of increasing concentrations of Hg(2+). The oxidation of -SH groups from a dithiol (DTT), a monothiol glutathione (GSH) and a protein (albumin) increased in the presence of Hg(2+). Only DTT was oxidized by Se(4+) and the oxidation decreased in the presence of Hg(2+), suggesting the formation of a chemical complex. This complex did not inhibit delta-ALA-D. These results suggest a similar inhibitory mechanism of Se(4+) and Hg(2+) on delta-ALA-D in which oxidation of sulfhydryl groups located at the active site of the enzyme is an essential step. Furthermore, decreasing oxidative effects of selenite on sulfhydryl groups from DTT in the presence of mercury are believed to occur as the result of the formation of an inactive ternary complex of the thiol-Hg-Se type, which does not inhibit delta-ALA-D.
Assuntos
Encéfalo/enzimologia , Rim/enzimologia , Fígado/enzimologia , Cloreto de Mercúrio/farmacologia , Sintase do Porfobilinogênio/antagonistas & inibidores , Selenito de Sódio/farmacologia , Animais , Masculino , Cloreto de Mercúrio/toxicidade , Camundongos , Oxirredução , Sintase do Porfobilinogênio/metabolismo , Ratos , Ratos Wistar , Selenito de Sódio/toxicidade , Compostos de Sulfidrila/metabolismoRESUMO
The aim of this study was to investigate the effects of chronically administered aluminum on erythropoiesis in rats. After treatment (i.p. injections of Al(2)(SO(4))(3), 50 micromol/kg body weight, five times a week) for 3 months, the treated (Al) group showed significantly decreased hemoglobin concentration (32%) and hematocrit (24%) compared with the control group. Serum iron decreased significantly in the Al group, whereas total iron binding capacity did not change. Treatment did not alter the activity of hepatic, renal or cerebral delta-ALA-D. Biochemical measurements related to 2-thiobarbituric acid-reactive substance (TBARS) levels from serum and hepatic, renal and cerebral homogenates also did not change after treatment. Hepatic concentrations of aluminum were higher in the Al group than in the control group. Renal and cerebral aluminum concentrations did not vary between groups. The present results indicate that exposure to aluminum sulfate promotes signs of anemia in rats as a consequence of alterations in iron status.