PMID- 17456591 OWN - NLM STAT- MEDLINE DCOM- 20070511 LR - 20131121 IS - 1099-8004 (Print) IS - 1099-8004 (Linking) VI - 8 IP - 4 DP - 2007 Apr TI - 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. PG - 300-4 AB - 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. FAU - McCullough, Karey D AU - McCullough KD AD - Nursing Faculty, Nipissing University, North Bay, Ontario, Canada. FAU - Bartfay, Wally J AU - Bartfay WJ LA - eng PT - Journal Article PL - United States TA - Biol Res Nurs JT - Biological research for nursing JID - 9815758 RN - 0 (Aldehydes) RN - 0 (Free Radicals) RN - 1406-18-4 (Vitamin E) RN - 4Y8F71G49Q (Malondialdehyde) RN - 9004-66-4 (Iron-Dextran Complex) RN - 9DC2K31JJQ (n-hexanal) SB - IM MH - Aldehydes/analysis/metabolism MH - Animals MH - Chronic Disease MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Drug Residues/analysis/metabolism MH - Free Radicals/analysis/metabolism MH - Gas Chromatography-Mass Spectrometry MH - Injections, Intraperitoneal MH - *Iron Overload/chemically induced/metabolism/pathology MH - Iron-Dextran Complex/*adverse effects MH - *Liver/chemistry/metabolism MH - Male MH - Malondialdehyde/analysis/metabolism MH - Mice MH - Mice, Inbred Strains MH - Random Allocation MH - Spectrophotometry, Atomic MH - *Vitamin E/analysis/metabolism EDAT- 2007/04/26 09:00 MHDA- 2007/05/12 09:00 CRDT- 2007/04/26 09:00 PHST- 2007/04/26 09:00 [pubmed] PHST- 2007/05/12 09:00 [medline] PHST- 2007/04/26 09:00 [entrez] AID - 8/4/300 [pii] AID - 10.1177/109980040629873 [doi] PST - ppublish SO - Biol Res Nurs. 2007 Apr;8(4):300-4. doi: 10.1177/109980040629873.