Mild iron overload effect on rat liver nuclei.
A single injection of iron-dextran significantly increased iron content in plasma, whole liver, cellular cytosol and liver nuclei. In vitro nuclear rate of Fe(3+)-EDTA reduction was not affected by the treatment. Membrane-bound enzymatic activities in the nuclei were measured after iron overload. Both NADPH- and NADH-dependent cytochrome c reductases were slightly decreased after iron overload, but cytochrome P450 was undetectable after 6 h of iron supplementation. The contents of lipid- and water-soluble antioxidants were measured in isolated nuclei from control and iron-overloaded rats. alpha-Tocopherol and beta-carotene co-elutant were decreased by 40% and 83%, respectively after 6 h of treatment. Nuclear glutathione content was not affected. The rate of generation of superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical-like species by isolated rat liver nuclei, were decreased by 50%, 40% and 60%, respectively after 6 h of iron supplementation. An identical qualitative response to iron overload was observed with NADPH and NADH. The inactivation of nuclear cytochrome P450, the significant loss in lipid-soluble antioxidants (alpha-tocopherol and beta-carotene) and the decrease in enzyme-dependent oxygen radical generation, suggest that the increase in catalytic active iron induced by iron overload could affect the cellular nuclei functionality.
Physical Chemistry Division, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
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Galleano
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Puntarulo
D000818:Animals; D000975:Antioxidants / Q000032:analysis; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D017665:Hydroxyl Radical; D007501:Iron / Q000633:toxicity*; D007505:Iron-Dextran Complex / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009245:NADH Dehydrogenase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D013481:Superoxides; D017665:Hydroxyl Radical; D007505:Iron-Dextran Complex; D007501:Iron; D009245:NADH Dehydrogenase