RESUMO
Hexachlorobenzene (HCB) induces a porphyria characterized by a diminished activity of the enzyme uroporphyrinogen decarboxylase (URO-D), presumably due to inactivation by reactive metabolites of HCB. We studied the effect of iron on HCB porphyria in female rats, to determine whether the iron dependent process of lipid peroxidation was involved in the pathogenesis of porphyria. We showed that malondialdehyde formation is increased in rat liver tissue of porphyric rats and that high molecular weight proteins due to cross-linking are formed. We also showed that the induction of porphyria by HCB is dependent on the presence of iron. Our findings suggest that lipid peroxidation is involved in the toxicity of HCB and that the aggravating effects of iron on HCB are mediated by lipid peroxidation.
Assuntos
Clorobenzenos/toxicidade , Hexaclorobenzeno/toxicidade , Ferro/fisiologia , Peróxidos Lipídicos/metabolismo , Porfirias/induzido quimicamente , Animais , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ratos , Ratos Endogâmicos , Uroporfirinogênio Descarboxilase/antagonistas & inibidoresRESUMO
1. Rat reticulocytes previously incubated with ((59)Fe, (125)I)-labelled transferrin were hemolysed to yield labelled ghosts. 2. The solubilized ghosts can be fractionated, by gel filtration on Sepharose 2B and 6B, into several (59)Fe- and (125)I-containing compounds, classified as A, B(1) and B(2). 3. These fractions were prepared from ghosts which were obtained at different centrifugation rates and further purified by sucrose density gradient centrifugation in order to obtain membrane compounds purified from mitochondrial and lysosomal impurities. The influence of these purification steps on the appearance and the (59)Fe/(125)I activity of the three components was investigated. 4. The first Sepharose 2B fraction with high molecular mass, greater than 10(6) daltons, is an intracellular product of mitochondrial and lysosomal origin which precipitates with the membrane fractions during the preparation of the ghost. The first Sepharose 6B fraction, B(1), with M(r) approximately 10(6) seems to be a real membrane component. The second Sepharose 6B fraction, B(2), with M(r) approximately 230 000 represents a real membrane receptor transferrin.
Assuntos
Membrana Eritrocítica/análise , Eritrócitos/análise , Ferro/sangue , Reticulócitos/análise , Animais , Fracionamento Celular , Centrifugação com Gradiente de Concentração , Cromatografia em Gel , Lisossomos/análise , Masculino , Mitocôndrias/análise , Ratos , Transferrina/análiseRESUMO
The haemoglobin, haematocrit, erythrocyte count, transferrin and serum iron values of a group of 65 healthy young people aging from 18-25 years were determined. Ferritin in serum was quantitated by radioimmunoassay to determine the usefulness of this assay in reflecting iron stores of healthy people.