Taurine prevents ethanol-induced apoptosis mediated by mitochondrial or death receptor pathways in liver cells

Amino Acids. 2018 Jul;50(7):863-875. doi: 10.1007/s00726-018-2561-3. Epub 2018 Apr 6.

Abstract

One pathogenic mechanism of ethanol-induced liver injury is the excessive production of reactive oxygen species (ROS), which may result in alcoholic liver disease (ALD) characterized by cell death due to necrosis and apoptosis. Taurine was proved to protect against liver damage. However, whether taurine attenuates ethanol-induced hepatic apoptosis remains unknown. The present study aims to elucidate this effect and its underlying mechanism. Taurine was administered to ALD rats and an in vitro experiment in which taurine was added to primary rat hepatocytes cultured with ethanol was conducted. Mitochondrial function and anti-oxidative capacity of the liver were tested. TUNEL and AO-EB double staining were conducted to detect apoptosis of liver cells. Expressions of factors and proteins involved in mitochondrial and death receptor pathways were detected by RT-PCR and Western-blot. The results showed that taurine inhibited the decline of cell functions and apoptosis in hepatocytes cultured with ethanol. Furthermore, increased malondialdehyde (MDA) and reduced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), cytochrome c oxidase (COX) and NADH dehydrogenase (ND) in ALD rats were mediated by taurine. RT-PCR and western-blot results revealed that taurine down-regulated expression of Bax, Fas, Fas ligand (FasL), caspase 3 and caspase 9 while up-regulating the expression of Bcl-2 in ethanol-cultured hepatocytes. In summary, taurine inhibit ethanol-induced hepatic apoptosis by regulating mitochondrial or death receptor pathways.

Keywords: Alcoholic liver disease; Apoptosis; Oxidative damage; Rat; Taurine.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Ethanol / adverse effects*
  • Ethanol / pharmacology
  • Hepatocytes / metabolism*
  • Hepatocytes / pathology
  • Liver Diseases, Alcoholic / drug therapy
  • Liver Diseases, Alcoholic / metabolism
  • Liver Diseases, Alcoholic / pathology
  • Male
  • Mitochondria, Liver / metabolism*
  • Mitochondria, Liver / pathology
  • Rats
  • Rats, Wistar
  • Receptors, Death Domain / metabolism*
  • Taurine / pharmacology*

Substances

  • Receptors, Death Domain
  • Taurine
  • Ethanol