BACKGROUND/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.
BACKGROUND/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% ferroceneiron; group 3 (Fe+Al), 0.75% iron and 7% ethanol; and group 4, 7% ethanol (Al) for 12 months. Iron profile, superoxide/nitritefree 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.
Authors: Al B Benson; Thomas A Abrams; Edgar Ben-Josef; P Mark Bloomston; Jean F Botha; Bryan M Clary; Anne Covey; Steven A Curley; Michael I D'Angelica; Rene Davila; William D Ensminger; John F Gibbs; Daniel Laheru; Mokenge P Malafa; Jorge Marrero; Steven G Meranze; Sean J Mulvihill; James O Park; James A Posey; Jasgit Sachdev; Riad Salem; Elin R Sigurdson; Constantinos Sofocleous; Jean-Nicolas Vauthey; Alan P Venook; Laura Williams Goff; Yun Yen; Andrew X Zhu Journal: J Natl Compr Canc Netw Date: 2009-04 Impact factor: 11.908
Authors: Erik R Anderson; Matthew Taylor; Xiang Xue; Angelical Martin; David S Moons; M Bishr Omary; Yatrik M Shah Journal: Mol Cell Biol Date: 2012-08-06 Impact factor: 4.272
Authors: Thomas Tu; Magdalena A Budzinska; Annette E Maczurek; Robert Cheng; Anna Di Bartolomeo; Fiona J Warner; Geoffrey W McCaughan; Susan V McLennan; Nicholas A Shackel Journal: Int J Mol Sci Date: 2014-05-27 Impact factor: 5.923