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Protection against CCl4-induced injury in liver by adenovirally introduced thioredoxin gene
Authors:Isoda Katsuhiro  Arita Eri  Kojima Midori  Ikkaku Masahiro  Tashiro Fumi  Yamato Eiji  Miyazaki Jun-ichi  Kawase Masaya  Kondoh Masuo  Yagi Kiyohito
Affiliation:Laboratory of Bio-functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Abstract:Antioxidation therapy is a promising strategy for treating or preventing oxidative stress-related liver diseases. The human thioredoxin (TRX) gene was inserted into an adenovirus vector (Adv-TRX), which was administered to mice. The mice were treated with 1 ml/kg CCl4 48 h after the infection. Blood samples were taken and the liver was excised 24 h after the CCl4 treatment. Serum ammonia, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were determined, and liver sections were stained with hematoxylin and eosin. RT-PCR analysis showed that the introduced TRX gene was expressed only in the liver. Adv-TRX decreased the serum ammonia, AST, and ALT levels. Hematoxylin-eosin staining indicated that the CCl4-induced injury was significantly prevented by the Adv-TRX infection. The gene delivery of TRX, which plays a central role in intracellular redox control, was shown to be effective in protecting the liver against oxidative stress-induced injury.
Keywords:Thioredoxin   Adenovirus vector   Gene therapy   Oxidative stress   Liver injury
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