BACKGROUND AND AIMS: Alcohol-induced liver injury is associated with an increase in oxidants from a variety of possible sources. Therefore, it was hypothesized that increased and stable expression of the antioxidant enzyme Cu/Zn-superoxide dismutase (SOD1) would diminish oxygen free radicals and reduce alcohol-induced liver injury. METHODS: To test this hypothesis, rats were given recombinant adenovirus containing Cu/Zn-superoxide dismutase (Ad.SOD1) or beta-galactosidase (Ad.lacZ) and fed ethanol enterally for 3 weeks. RESULTS: SOD was increased significantly 3-5-fold over endogenous levels in both hepatocytes as well as Kupffer cells 3 weeks after infection. Serum transaminase levels and pathology were elevated significantly in Ad.lacZ-treated animals by using an intragastric feeding model. This effect was blunted significantly in Ad.SOD1-infected animals. Importantly, electron spin resonance-detectable free-radical adducts caused by ethanol were also decreased by SOD1 overexpression. Moreover, the increase in nuclear factor kappaB (NFkappaB), tumor necrosis factor alpha (TNF-alpha), and interleukin 1 messenger RNA (mRNA) caused by ethanol was blunted in animals treated with Ad.SOD1. CONCLUSIONS: These data support the hypothesis that oxidant production is critical in early alcohol-induced liver injury and that gene delivery of antioxidant enzymes may be useful in prevention and treatment.
BACKGROUND AND AIMS: Alcohol-induced liver injury is associated with an increase in oxidants from a variety of possible sources. Therefore, it was hypothesized that increased and stable expression of the antioxidant enzyme Cu/Zn-superoxide dismutase (SOD1) would diminish oxygen free radicals and reduce alcohol-induced liver injury. METHODS: To test this hypothesis, rats were given recombinant adenovirus containing Cu/Zn-superoxide dismutase (Ad.SOD1) or beta-galactosidase (Ad.lacZ) and fed ethanol enterally for 3 weeks. RESULTS:SOD was increased significantly 3-5-fold over endogenous levels in both hepatocytes as well as Kupffer cells 3 weeks after infection. Serum transaminase levels and pathology were elevated significantly in Ad.lacZ-treated animals by using an intragastric feeding model. This effect was blunted significantly in Ad.SOD1-infected animals. Importantly, electron spin resonance-detectable free-radical adducts caused by ethanol were also decreased by SOD1 overexpression. Moreover, the increase in nuclear factor kappaB (NFkappaB), tumor necrosis factor alpha (TNF-alpha), and interleukin 1 messenger RNA (mRNA) caused by ethanol was blunted in animals treated with Ad.SOD1. CONCLUSIONS: These data support the hypothesis that oxidant production is critical in early alcohol-induced liver injury and that gene delivery of antioxidant enzymes may be useful in prevention and treatment.
Authors: Martin J J Ronis; Angelica Butura; Brante P Sampey; Kartik Shankar; Ronald L Prior; Sohelia Korourian; Emanuele Albano; Magnus Ingelman-Sundberg; Dennis R Petersen; Thomas M Badger Journal: Free Radic Biol Med Date: 2005-09-01 Impact factor: 7.376
Authors: Shiguang Liu; Tzu-Hsuan Yeh; Vijay P Singh; Sruti Shiva; Lindsay Krauland; Huanan Li; Pili Zhang; Kusum Kharbanda; Vladimir Ritov; Satdarshan P S Monga; Donald K Scott; Patricia K Eagon; Jaideep Behari Journal: Hepatology Date: 2012-03 Impact factor: 17.425
Authors: Zhanxiang Zhou; Lipeng Wang; Zhenyuan Song; Jason C Lambert; Craig J McClain; Y James Kang Journal: Am J Pathol Date: 2003-09 Impact factor: 4.307