Protection against CCl4-induced injury in liver by adenovirally introduced thioredoxin gene.
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.
Isoda
Katsuhiro
K
Laboratory of Bio-functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Arita
Eri
E
Kojima
Midori
M
Ikkaku
Masahiro
M
Tashiro
Fumi
F
Yamato
Eiji
E
Miyazaki
Jun-ichi
J
Kawase
Masaya
M
Kondoh
Masuo
M
Yagi
Kiyohito
K
D000256:Adenoviridae / Q000235:genetics*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D051381:Rats; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism*
C491203:TXN protein, human; D013879:Thioredoxins; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase