Synergistic Interaction between Excess Hepatic Iron and Alcohol Ingestion in Hepatic Mutagenesis.

dc.contributor.authorAsare, A.G.
dc.contributor.authorMichelle, B.
dc.contributor.authorVivash, N.
dc.contributor.authorKew, C.M.
dc.date.accessioned2013-01-03T12:06:41Z
dc.date.accessioned2017-10-16T11:37:49Z
dc.date.available2013-01-03T12:06:41Z
dc.date.available2017-10-16T11:37:49Z
dc.date.issued2008
dc.description.abstractBACKGROUND/AIM Hereditary hemochromatosis (HH) and dietary iron overload are the main iron-loading diseases. Fibrosis, cirrhosis and hepatocellular carcinoma (HCC) are complications to HH and dietary iron overload possibly influenced by co-factors. Alcohol may be one such factor. The aim therefore was to determine the extent of synergistic interaction between free hepatic iron and alcohol, complicating dietary iron overload in HCC pathogenesis. METHODS: Four groups of 20 Wistar albino rats were used: group 1 (C) was fed the chow diet; group 2 (Fe) was supplemented with 0.75% ferrocene iron; group 3 (Fe+Al), 0.75% iron and 7% ethanol; and group 4, 7% ethanol (Al) for 12 months. Iron profile, superoxide/nitrite free radicals, lipid peroxidation (LPO)/8-isoprostane (8-IP), 8-hydroxydeoxyguanosine (8-OHdG), oxidative lipid/DNA damage immunohistochemistry, transaminases (AST/ALT) and Ames mutagenesis tests were performed. RESULTS: Significant differences were observed in the Fe+Al group for LPO, 8-IP, AST and ALT (p<0.001, 0.001, 0.001 and 0.001, respectively) compared to other groups. A three-fold synergistic interaction was observed for the same parameters. Furthermore, significant differences of p<0.05 and 0.001 were observed for 8-OHdG and mutagenesis, respectively, with an additive synergy in the Fe+Al group. ALT/8-OHdG and ALT/mutagenesis correlated positively (p<0.04 and 0.008, respectively). The immunohistochemistry revealed iron/alcohol multiplicative synergism with hydroxyl radical involvement. CONCLUSION: Mutagenic effects of iron and alcohol are synergistically multiplicative implicating hydroxyl free radicals in hepatocarcingenesis.en_US
dc.identifier.citationToxicology 254:11-18.en_US
dc.identifier.urihttp://197.255.68.203/handle/123456789/2350
dc.language.isoenen_US
dc.publisherElsevier, Irelanden_US
dc.subjectIron overloaden_US
dc.subjectAlcoholen_US
dc.subjectSynergyen_US
dc.subjectMutagenesisen_US
dc.subjectp53 mutationen_US
dc.titleSynergistic Interaction between Excess Hepatic Iron and Alcohol Ingestion in Hepatic Mutagenesis.en_US
dc.typeArticleen_US

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