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Effect of iron overload on spontaneous and xenobiotic‐induced lipid peroxidation in vivo
Author(s) -
Younes M.,
Eberhardt I.,
Lemoine R.
Publication year - 1989
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550090206
Subject(s) - lipid peroxidation , chemistry , in vivo , bromobenzene , biochemistry , medicine , endocrinology , xenobiotic , toxicity , pharmacology , enzyme , biology , microbiology and biotechnology , organic chemistry , catalysis
To study the effect of iron‐overload on hepatic lipid peroxidation, two rat models of haemochromatosis were employed: in the first model resembling secondary haemochromatosis, repeated i.p. injections with Fe‐dextran led to an accumulation of Fe in Kupffer cells, while in the second model resembling hereditary haemochromatosis, iron was located mainly in periportal hepatocytes after feeding on a diet containing 3.5% Fe‐fumarate for 3 weeks. In both models, total hepatic iron content was elevated four‐ to fivefold over controls. In vivo lipid peroxidation (ethane exhalation) was enhanced only in the second model, indicating that the hepatocytes are the main targets of Fe‐induced lipid peroxidation. Low hepatotoxicity was observed in the second model. Additional treatment of the rats with hepatotoxic agents led to different results: with ethanol and bromobenzene, lipid peroxidation was only evident in both models of iron‐overload, while paracetamol‐induced lipid peroxidation was seen only in Fe‐fumarate‐fed rats. CCl 4 ‐induced lipid peroxidation was strongly enhanced in both models of haemochromatosis. Hepatotoxicity was enhanced by iron overload only in the case of CCl 4 treated, Fe‐fumarate‐fed rats. The activities of phase I and phase II enzymes of xenobiotic metabolism were not markedly altered in livers of iron‐overloaded rats. This implies that neither the bioactivation nor the detoxification of the agents studied were affected in experimental haemochromatosis.