Branched-chain amino acid-enriched nutrients stimulate antioxidant DNA repair in a rat model of liver injury induced by carbon tetrachloride.
Oxidative stress (OS) plays an important role in the progression of chronic liver disease including organ injury and hypoalbuminemia. Long-term oral supplementation with branched-chain amino acids (BCAAs) can inhibit liver dysfunction but their role in the prevention of liver fibrosis and injury to the liver is unclear. The aim of this study was to assess how BCAAs preserve liver function from OS. To investigate how BCAAs specifically prevent OS, we evaluated the effect of oral supplementation with BCAAs on OS using a rat liver cirrhosis model. Liver cirrhosis was induced in ten male Sprague-Dawley rats by administering carbon tetrachloride for 12 weeks. Five of the ten carbon tetrachloride-treated rats were assigned to a control group and five to a BCAA group. BCAA-supplementation significantly preserved plasma albumin concentrations and significantly inhibited the occurrence of organ injury as determined by blood chemistry analysis. Hepatic expression of OGG1 mRNA was increased in the BCAA group compared to the control group. In the BCAA group, increased hepatic levels of OGG1 protein were found by western blot. On the other hand, the number of 8-OHdG-positive cells was significantly higher in liver sections taken 1 month after carbon tetrachloride treatment. Furthermore, OGG1-positive cells were significantly increased in the hepatocytes around the central vein. BCAA was found to reduce OS, which could possibly lead to a decrease in the occurrence of hypoalbuminemia and organ injury. Our results indicate that BCAA-enriched nutrients stimulate antioxidant DNA repair in a rat model of liver injury induced by carbon tetrachloride.
Regenerative Medicine Group, Center for Innovative and Translational Medicine, Department of Surgery at Kochi Medical School, Kochi University, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan.
Kengo
K
Ichikawa
Takehiro
T
Okabayashi
Yasuo
Y
Shima
Tatsuo
T
Iiyama
Yuka
Y
Takezaki
Masaya
M
Munekage
Tsutomu
T
Namikawa
Takeki
T
Sugimoto
Michiya
M
Kobayashi
Toshiki
T
Mimura
Kazuhiro
K
Hanazaki
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000597:Amino Acids, Branched-Chain / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D016207:Cytokines / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005502:Food; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000597:Amino Acids, Branched-Chain; D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002251:Carbon Tetrachloride; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D003849:Deoxyguanosine