title: The dose-dependent effects of chronic iron overload on the production of oxygen free radicals and vitamin E concentrations in the liver of a murine model.
abstract: Genetic disorders of iron metabolism such as primary and secondary hemochromatosis affect thousands of individuals worldwide and are major causes of liver dysfunction, morbidity, and mortality. Although the exact mechanism of hepatic injury associated with these genetic disorders is not fully understood, the propagation of excess concentrations of iron-catalyzed oxygen free radicals (OFRs) may play a role. The authors hypothesized that chronic iron burden would result in dose-dependent (a) increases in hepatic iron stores, (b) increases in hepatic OFR-mediated hepatic cellular injury as quantified by the cytotoxic aldehydes malondialdehyde (MDA) and hexanal, and (c) decreases in protective antioxidant reserve status as quantified by plasma vitamin E (alpha-tocopherol) levels in a murine model. Twenty B(6)D(2)F1 male mice were randomized to the (a) saline control (0.05 mL intraperiotoneal [i.p.]/mouse/day, n = 5), (b) 100 mg total iron burden (n = 5), (c) 200 mg total iron burden (n = 5), or (d) 400 mg total iron burden (n = 5) group. Iron burden was achieved by daily injections of iron dextran (Imferon, 0.05 mL i.p./mouse/day). In comparison to control mice and in support of the hypothesis, the authors observed significant dose-dependent increases in total hepatic iron burden (p < .001) with corresponding increases in MDA and hexanal concentrations (p < .001) and decreases in the protective plasma antioxidant vitamin E (p < .001). These findings suggest that iron-catalyzed OFR-mediated damage may play a role in damaging the liver in chronic states of iron burden.
authors: Nursing Faculty, Nipissing University, North Bay, Ontario, Canada.
authors: Karey D
authors: KD
authors: McCullough
authors: Wally J
authors: WJ
authors: Bartfay
mesh_terms: D000447:Aldehydes / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004350:Drug Residues / Q000032:analysis / Q000378:metabolism; D005609:Free Radicals / Q000032:analysis / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D007274:Injections, Intraperitoneal; D019190:Iron Overload / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007505:Iron-Dextran Complex / Q000009:adverse effects*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011897:Random Allocation; D013054:Spectrophotometry, Atomic; D014810:Vitamin E / Q000032:analysis / Q000378:metabolism
chemical_list: D000447:Aldehydes; D005609:Free Radicals; D014810:Vitamin E; D008315:Malondialdehyde; D007505:Iron-Dextran Complex; C010463:n-hexanal