Spontaneous and xenobiotic-induced in vivo-lipid peroxidation in iron-overloaded rats.

Abstract

Iron ions play a major role in initiation and propagation reactions of enzymatic lipid peroxidation (LPO) (Aust et al 1985). Recently, it has been shown that chelation of endogenous iron by deferrioxamine, a specific high affinity iron chelator, resulted in an inhibition of acetaminophen- and CCl4-induced in vivo-lipid peroxidation (Younes and Siegers 1985). Similar results were obtained with bro-mobenzene (Casini et al 1987) and allyl alcohol (Jaeschke et al 1987), indicating that ionized iron is involved in xenobiotic-induced lipid peroxidation. On the other hand, simultaneous treatment with iron was shown to potentiate the prooxidative action of acetaminophen (Younes et al 1986), adriamycin (Muliawan et al 1986), CC14 (Muliawan and Kappus 1983), and ethanol (Nordmann et al 1987). In hemochromatosis (HC), excessive iron is progressively deposited in parenchymal cells of the liver, besides heart and endocrine glands (Powell 1975). Liver damage resulting from this condition, has been partly attributed to membrane lipid peroxidation of mitochondria and microsomes with subsequent cell injury and cell death (Bacon et al 1983, 1985). In this study, the effect of experimental iron-overload on lipid peroxidation induced by acetaminophen, ethanol, bromobenzene and CC14 was investigated using two rat models resembling hereditary and secondary HC, respectively.