Skip to main content
Log in

Protective effect of gamma-aminobutyric acid (GABA) against cytotoxicity of ethanol in isolated rat hepatocytes involves modulations in cellular polyamine levels

  • Published:
Amino Acids Aims and scope Submit manuscript

Summary.

Gamma-aminobutyric acid (GABA) is considered to be a multifunctional molecule with various physiological effects throughout the body. It is also evident that the liver contains GABA and its transporter. However, the functions of GABA in liver have not been well documented. In this study, the cytoprotective effect of GABA against ethanol-induced hepatotoxicity was evaluated in primary cultured rat hepatocytes. Addition of ethanol induced decrease of cell viability in a dose-dependent manner. However, treatment with GABA resulted in a dose-dependent recovery from ethanol (150 mM)-induced cytotoxicity.

GABA reversed the ethanol-induced decrease in intracellular polyamine levels. Furthermore, the addition of polyamines also reversed the ethanol-induced decrease of cell viability. These results suggest that GABA is protective against the cytotoxicity of ethanol in isolated rat hepatocytes and this effect may be modulated by the maintenance of intracellular polyamine levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • M Adachi H Ishii (2002) ArticleTitleRole of mitochondria in alcoholic liver injury Free Radic Biol Med 32 487–491 Occurrence Handle11958949 Occurrence Handle10.1016/S0891-5849(02)00740-2 Occurrence Handle1:CAS:528:DC%2BD38Xhs1yls7o%3D

    Article  PubMed  CAS  Google Scholar 

  • T Arimura A Kojima-Yuasa Y Tatsumi DO Kennedy I Matsui-Yuasa (2005) ArticleTitleInvolvement of polyamines in evening primrose extract-induced apoptosis in Ehrlich ascites tumor cells Amino Acids 28 21–27 Occurrence Handle15700107 Occurrence Handle10.1007/s00726-004-0155-8 Occurrence Handle1:CAS:528:DC%2BD2MXhsVKqs7o%3D

    Article  PubMed  CAS  Google Scholar 

  • HU Bergmeyer E Bernt B Hess (1965) Lactate dehydrogenase HU Bergmeyer (Eds) Methods of enzymatic analysis Academic Press New York 736–743

    Google Scholar 

  • K Burton (1968) ArticleTitleDeterminations of DNA concentration with diphenylamine Methods Enzymol 12B 163–166

    Google Scholar 

  • R Castilla R Gonzalez D Fouad E Fraga J Muntane (2004) ArticleTitleDual effect of ethanol on cell death in primary culture of human and rat hepatocytes Alcohol 39 290–296 Occurrence Handle1:CAS:528:DC%2BD2cXltVWnu7o%3D

    CAS  Google Scholar 

  • W Chen DO Kennedy A Kojima I Matsui-Yuasa (2000) ArticleTitlePolyamines and thiols in the cytoprotective effect of L-cysteine and L-methionine on carbon tetrachloride-induced hepatotoxicity Amino Acids 18 319–327 Occurrence Handle10949915 Occurrence Handle10.1007/s007260070071 Occurrence Handle1:CAS:528:DC%2BD3cXlvVGhtrc%3D

    Article  PubMed  CAS  Google Scholar 

  • RD Goldin NC Hunt J Clark SN Wickramasinghe (1993) ArticleTitleApoptotic bodies in a murine model of alcoholic liver disease: reversibility of ethanol-induced changes J Pathol 171 73–76 Occurrence Handle8229461 Occurrence Handle10.1002/path.1711710115 Occurrence Handle1:STN:280:DyaK2c%2Fks1Wqtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Gong M Zhang L Cui GY Minuk (2001) ArticleTitleSequence and chromosomal assignment of a human novel cDNA: similarity to gamma-aminobutyric acid transporter Can J Physiol Pharmacol 79 977–984 Occurrence Handle11824941 Occurrence Handle10.1139/cjpp-79-12-977 Occurrence Handle1:CAS:528:DC%2BD38XoslKgug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • K Henzel C Thorborg M Hofmann G Zimmer U Leuschner (2004) ArticleTitleToxicity of ethanol and acetaldehyde in hepatocytes treated with ursodeoxycholic or tauroursodeoxycholic acid Biochim Biophys Acta 1644 37–45 Occurrence Handle14741743 Occurrence Handle10.1016/j.bbamcr.2003.10.017 Occurrence Handle1:CAS:528:DC%2BD2cXntFSjtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • A Kasdallah-Grissa B Mornagui E Aouani M Hammami N Gharbi A Kamoun S El-Fazaa (2006) ArticleTitleProtective effect of resveratrol on ethanol-induced lipid peroxidation in rats Alcohol 41 236–239 Occurrence Handle1:CAS:528:DC%2BD28XjvF2kurc%3D

    CAS  Google Scholar 

  • RF Klein KA Fausti AS Carlos (1996) ArticleTitleEthanol inhibits human osteoblastic cell proliferation Alcohol Clin Exp Res 20 572–578 Occurrence Handle8727257 Occurrence Handle10.1111/j.1530-0277.1996.tb01095.x Occurrence Handle1:CAS:528:DyaK28Xjsleru70%3D

    Article  PubMed  CAS  Google Scholar 

  • YJ Lee AR Aroor SD Shukla (2002) ArticleTitleTemporal activation of p42/44 mitogen-activated protein kinase and c-Jun N-terminal kinase by acetaldehyde in rat hepatocytes and its loss after chronic ethanol exposure J Pharmacol Exp Ther 301 908–914 Occurrence Handle12023518 Occurrence Handle10.1124/jpet.301.3.908 Occurrence Handle1:CAS:528:DC%2BD38XktlGjs7o%3D

    Article  PubMed  CAS  Google Scholar 

  • LJ Levy J Leek MS Losowsky (1987) ArticleTitleEvidence for gamma-aminobutyric acid as the inhibitor of gamma-aminobutyric acid binding in the plasma of humans with liver disease and hepatic encephalopathy Clin Sci (Lond) 73 531–534 Occurrence Handle1:CAS:528:DyaL2sXmtlCitLg%3D

    CAS  Google Scholar 

  • AJ McCullough (1999) Alcohol liver disease ER Schiff MF Sorrell WC Maddrey (Eds) Schiff’s diseases of the liver Lippincott-Raven Philadelphia 941–971

    Google Scholar 

  • GY Minuk (1993) ArticleTitleGamma-aminobutyric acid and the liver Dig Dis 11 45–54 Occurrence Handle8383020 Occurrence Handle1:STN:280:DyaK3s7osFarsA%3D%3D Occurrence Handle10.1159/000171400

    Article  PubMed  CAS  Google Scholar 

  • GY Minuk T Gauthier XK Zhang GQ Wang NM Pettigrew FJ Burczynski (1995) ArticleTitleCiprofloxacin prevents the inhibitory effects of acute ethanol exposure on hepatic regeneration in the rat Hepatology 22 1797–1800 Occurrence Handle7489991 Occurrence Handle1:CAS:528:DyaK28XmvV2ktA%3D%3D

    PubMed  CAS  Google Scholar 

  • P Moldeus J Hogberg S Orrenius (1978) ArticleTitleIsolation and use of liver cells Methods Enzymol 52 60–71 Occurrence Handle672656 Occurrence Handle1:CAS:528:DyaE1MXjs1Sisg%3D%3D Occurrence Handle10.1016/S0076-6879(78)52006-5

    Article  PubMed  CAS  Google Scholar 

  • S Nagoshi Y Ohta A Matsui K Fujiwara (1994) ArticleTitleProtective action of putrescine against rat liver injury Scand J Gastroenterol 29 166–171 Occurrence Handle8171286 Occurrence Handle1:CAS:528:DyaK2cXkt1Kls70%3D

    PubMed  CAS  Google Scholar 

  • LE Nagy (2004) ArticleTitleMolecular aspects of alcohol metabolism: transcription factors involved in early ethanol-induced liver injury Annu Rev Nutr 24 55–78 Occurrence Handle15189113 Occurrence Handle10.1146/annurev.nutr.24.012003.132258 Occurrence Handle1:CAS:528:DC%2BD2cXlvFKksrs%3D

    Article  PubMed  CAS  Google Scholar 

  • S Natori C Rust LM Stadheim A Srinivasan LJ Burgart GJ Gores (2001) ArticleTitleHepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis J Hepatol 34 248–253 Occurrence Handle11281553 Occurrence Handle10.1016/S0168-8278(00)00089-1 Occurrence Handle1:CAS:528:DC%2BD3MXislCksLk%3D

    Article  PubMed  CAS  Google Scholar 

  • S Nishiguchi T Kuroki T Takeda S Nakajima S Shiomi S Seki I Matsui-Yuasa S Otani K Kobayashi (1990) ArticleTitleEffects of putrescine on D-galactosamine-induced acute liver failure in rats Hepatology 12 348–353 Occurrence Handle2391073 Occurrence Handle10.1002/hep.1840120224 Occurrence Handle1:CAS:528:DyaK3cXmt1Cmtrg%3D

    Article  PubMed  CAS  Google Scholar 

  • J Ostrowska W Luczaj I Kasacka A Rozanski E Skrzydlewska (2004) ArticleTitleGreen tea protects against ethanol-induced lipid peroxidation in rat organs Alcohol 32 25–32 Occurrence Handle15066700 Occurrence Handle10.1016/j.alcohol.2003.11.001 Occurrence Handle1:CAS:528:DC%2BD2cXivVWrtLY%3D

    Article  PubMed  CAS  Google Scholar 

  • RG Schipper LC Penning AA Verhofstad (2000) ArticleTitleInvolvement of polyamines in apoptosis. Facts and controversies: effectors or protectors? Semin Cancer Biol 10 55–68 Occurrence Handle10888272 Occurrence Handle10.1006/scbi.2000.0308 Occurrence Handle1:CAS:528:DC%2BD3cXkvFWkt7k%3D

    Article  PubMed  CAS  Google Scholar 

  • N Seiler JG Delcros JP Moulinoux (1996) ArticleTitlePolyamine transport in mammalian cells. An update Int J Biochem Cell Biol 28 843–861 Occurrence Handle8811834 Occurrence Handle10.1016/1357-2725(96)00021-0 Occurrence Handle1:CAS:528:DyaK28XlvVGnsbY%3D

    Article  PubMed  CAS  Google Scholar 

  • A Sessa A Perin (1997) ArticleTitleEthanol and polyamine metabolism: physiologic and pathologic implications: a review Alcohol Clin Exp Res 21 318–325 Occurrence Handle9113270 Occurrence Handle1:CAS:528:DyaK2sXjt1eisLk%3D

    PubMed  CAS  Google Scholar 

  • IA Shibley SuffixJr MD Gavigan SN Pennington (1995) ArticleTitleEthanol’s effect on tissue polyamines and ornithine decarboxylase activity: a concise review Alcohol Clin Exp Res 19 209–215 Occurrence Handle7771652 Occurrence Handle10.1111/j.1530-0277.1995.tb01494.x Occurrence Handle1:CAS:528:DyaK2MXksFegsbY%3D

    Article  PubMed  CAS  Google Scholar 

  • T Tanaka S Nishiguchi T Kuroki K Kobayashi I Matsui-Yuasa S Otani T Toda T Monna Y Sukegawa (1991) ArticleTitleEffects of single ethanol administration on hepatic ornithine decarboxylase induction and polyamine metabolism Hepatology 14 696–700 Occurrence Handle1916673 Occurrence Handle1:CAS:528:DyaK3MXmsFSitro%3D Occurrence Handle10.1002/hep.1840140420

    Article  PubMed  CAS  Google Scholar 

  • KN Tzirogiannis GI Panoutsopoulos MD Demonakou GK Papadimas VG Kondyli KT Kourentzi RI Hereti MG Mykoniatis (2004) ArticleTitleThe hepatoprotective effect of putrescine against cadmium-induced acute liver injury Arch Toxicol 78 321–329 Occurrence Handle15004664 Occurrence Handle10.1007/s00204-004-0549-0 Occurrence Handle1:CAS:528:DC%2BD2cXks1Kmt78%3D

    Article  PubMed  CAS  Google Scholar 

  • AL Vahrmeijer JH van Dierendonck J Schutrups CJ van de Velde GJ Mulder (1999) ArticleTitleEffect of glutathione depletion on inhibition of cell cycle progression and induction of apoptosis by melphalan (L-phenylalanine mustard) in human colorectal cancer cells Biochem Pharmacol 58 655–664 Occurrence Handle10413303 Occurrence Handle10.1016/S0006-2952(99)00130-6 Occurrence Handle1:CAS:528:DyaK1MXks1WrsLY%3D

    Article  PubMed  CAS  Google Scholar 

  • S Vemulapalli M Barletta (1984) ArticleTitleThe role of the sympathetic nervous system in the cardiovascular effects of systemically administered gamma-aminobutyric acid Arch Int Pharmacodyn Ther 267 46–58 Occurrence Handle6144293 Occurrence Handle1:CAS:528:DyaL2cXhtleitb8%3D

    PubMed  CAS  Google Scholar 

  • C Wu C Miyagawa DO Kennedy Y Yano S Otani I Matsui-Yuasa (1997) ArticleTitleInvolvement of polyamines in the protection of taurine against the cytotoxicity of hydrazine or carbon tetrachloride in isolated rat hepatocytes Chem Biol Interact 103 213–224 Occurrence Handle9134011 Occurrence Handle10.1016/S0009-2797(96)03760-X Occurrence Handle1:CAS:528:DyaK2sXis1eiu7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • SZ Zhang MM Lipsky BF Trump IC Hsu (1990) ArticleTitleNeutral red (NR) assay for cell viability and xenobiotic-induced cytotoxicity in primary cultures of human and rat hepatocytes Cell Biol Toxicol 6 219–234 Occurrence Handle2113829 Occurrence Handle10.1007/BF00249595 Occurrence Handle1:CAS:528:DyaK38XkvVCktr0%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Norikura, T., Kojima-Yuasa, A., Opare Kennedy, D. et al. Protective effect of gamma-aminobutyric acid (GABA) against cytotoxicity of ethanol in isolated rat hepatocytes involves modulations in cellular polyamine levels. Amino Acids 32, 419–423 (2007). https://doi.org/10.1007/s00726-006-0381-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-006-0381-3

Navigation