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Protective effect of gamma‐aminobutyric acid (GABA) against cytotoxicity of ethanol in isolated rat hepatocytes involves modulations in cellular polyamine levels
Author(s) -
Norikura Toshio,
KojimaYuasa Akiko,
Suzuura Chie,
MatsuiYuasa Isao
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a570-c
Subject(s) - polyamine , spermine , spermidine , viability assay , cytotoxicity , intracellular , putrescine , ethanol , chemistry , hepatocyte , biochemistry , gamma aminobutyric acid , pharmacology , cell , microbiology and biotechnology , biology , in vitro , enzyme , receptor
GABA is a potent amino acid neurotransmitter with various physiologic effects throughout the body. Serum concentration of GABA is known to be increased in liver failure. However, the function of GABA in liver is not clear. In this study, we investigated the involvement of modulations in cellular polyamine levels on the protective effect of GABA against cytotoxicity of ethanol in isolated rat hepatocytes. Method Hepatocytotoxicity was induced by the addition of ethanol. Viability of hepatocytes with or without GABA and polyamine was evaluated by Neutral Red assay. We used HPLC method with fluorometric detection to measure levels of intracellular putrescine (PUT), spermidine (SPD) and spermine (SPM) which are major polyamines ubiquitously present in eukaryotic cells. Result The addition of ethanol to hepatocyte induced a decrease in cell viability. However, incubation with GABA significantly prevented this decrease in a dose‐dependent manner. Ethanol also resulted in a loss of PUT and SPD levels and the loss was significantly returned to control levels by the addition of GABA. Furthermore, the decrease in cell viability induced by ethanol was significantly suppressed by supplementation of PUT and SPD. Conclusion These results suggest that GABA has protective effect against cytotoxicity of ethanol in isolated rat hepatocytes. This effect may be modulated by the maintenance of intracellular polyamine levels.