RESUMO
Cadmium exposure induces low birth weight through unknown mechanisms. Since low birth weight is associated to foetal exposure to high glucocorticoids (GC) concentrations, we hypothesized that low birth weight induced by prenatal exposure to Cd(2+) is, at least in part, mediated by higher foetal exposure to GC, specifically corticosterone, the main active GC in rodents. Pregnant rats were exposed to different dose of CdCl(2) administered in drinking water during the whole pregnancy period. At term, corticosterone was measured by enzyme immunoassay in maternal and foetal blood and in placental tissues. Cadmium was determined in placentas, maternal tissues (liver and kidney) and foetuses by inductively coupled plasma-mass spectrometry (ICP-MS). Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and expression were determined by a radiometric conversion assay and quantitative RT-PCR respectively. Results demonstrated that 50 ppm of Cd(2+), which was accumulated in different maternal tissues but not in the foetus, reduced pup birth weights and increased plasma corticosterone concentrations, both in mother and foetus. Placental 11beta-HSD2 activity and expression did not change by the treatment. We conclude that 50 ppm of Cd(2+) administered during pregnancy, increase foetal corticosterone concentrations due, probably, to alterations of the regulatory mechanisms of placental barrier to GC causing a mild but significant reduced birth weight.
Assuntos
Peso ao Nascer/efeitos dos fármacos , Cloreto de Cádmio/toxicidade , Corticosterona/sangue , Poluentes Ambientais/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Exposição Materna/efeitos adversos , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/biossíntese , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Animais , Cloreto de Cádmio/sangue , Cloreto de Cádmio/farmacocinética , Poluentes Ambientais/sangue , Poluentes Ambientais/farmacocinética , Feminino , Sangue Fetal/química , Placenta/efeitos dos fármacos , Placenta/enzimologia , Placenta/metabolismo , Gravidez , Ratos , Ratos WistarRESUMO
The heavy metal cadmium is very toxic to biological systems. Although its effect on the growth of microorganisms and plants has been investigated, the response of antioxidant enzymes of Aspergillus nidulans to cadmium is not well documented. We have studied the effect of cadmium (supplied as CdCl(2)) on catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR). 0.005 mM CdCl(2) had a very slight stimulatory effect on the growth rate of A. nidulans, but at concentrations above 0.025 mM, growth was totally inhibited. The accumulation of Cd within the mycelium was directly correlated with the increase in the concentration of CdC(2) used in the treatments. Although a cadmium-stimulated increase in SOD activity was observed, there was no change in the relative proportions of the individual Mn-SOD isoenzymes. Higher concentrations of CdCl(2) induced a small increase in total CAT activity, but there was a major increase in one isoenzymic form, that could be separated by gel electrophoresis. GR activity increased significantly following treatment with the highest concentration (0.05 mM) of CdCl(2). The increases in SOD, CAT, and GR activities suggest that CdCl(2) induces the formation of reactive oxygen species inside the mycelia of A. nidulans.