Effect of iron overload on spontaneous and xenobiotic‐induced lipid peroxidation in vivo

Abstract

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. CCl4-induced lipid peroxidation was strongly enhanced in both models of haemochromatosis. Hepatotoxicity was enhanced by iron overload only in the case of CCl4-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.

Effects of Iron Overload on Hepatic and Renal Metallothionein Levels in Rats

“…8) In the present study, the hepatic Fe levels increased up to 7.2-fold of the control group after 21 days ( Table 1). The increase in the renal Fe levels was more moderate than in the liver levels.…”

“…[6][7][8] Younes et al 8) reported that rats fed on a diet containing 3.5% Fe(II) fumarate enhanced a susceptibility to xenobiotics-induced hepatic damage via selective accumulation of Fe in the hepatocytes. Previously, the authors suggested the enhanced production of *To whom correspondence should be addressed: Biochemistry Section, National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan.…”

Dietary Intrinsic Phytate Protects Colon from Lipid Peroxidation in Pigs with a Moderately High Dietary Iron Intake

“…Whereas 80 mgkg is the quantity of iron normally supplemented in practical diets for growing pigs, 750 mgkg were used to resemble the levels of consumption of this mineral by certain population groups whose iron intake approximates eight times the normal requirements (36). Yet, this level is much lower than those used in most iron-overload studies (40,41).…”

Nitric oxide and iron: effect of iron overload on nitric oxide production in endotoxemia

“…Liver is the main organ for iron storage (Papanastasiou et al, 2000) and human iron overload is characteristic of genetic hemochromatosis and of excess blood transfusions (Halliday and Searle, 1996;Stal et al, 1995). Treatment of rats with iron-dextran resembles the hemochromatosis secondary to iron loaded anemias (anemias treated with repeated transfusions) and high iron oral intake (Younes et al, 1969;Powell et al, 1980). Treatments with parenteral iron or with iron-dextran determine that the cells of the reticuloendothelial system accumulate the majority of the taken up iron.…”