Effects of ethanol and acetaldehyde on reactive oxygen species production in rat hepatic stellate cells

Gennadiy Novitskiy, Kassim Traore, Lan Wang, Michael A. Trush, Esteban Mezey

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Alcoholism is a common cause of cirrhosis. Hepatic stellate cells are the main source of collagen that ultimately leads to hepatic fibrosis and cirrhosis. Reactive oxygen species (ROS) enhance stellate cell activation and stimulate fibrogenesis. In this study, the acute effects of ethanol (ET) and acetaldehyde (AC) were determined on the production of ROS in isolated rat hepatic stellate cells. Methods: Rat stellate cells were isolated in situ by perfusion of the portal vein and cultured. Hydrogen peroxide (H 2O2) was determined by luminol-derived chemiluminescence (CL), while superoxide anion (O2•-) production was assessed by the fluorescent probe hydroethidine. Results: AC increased the formation of H2O2 and O2•-, and these effects were first detectable at AC concentrations of 5 and 10 μM, respectively, reaching a maximum at 50 to 75 μM. Reduction of glutathione (GSH) synthesis by 1-buthionine sulfoximide (BSO) or by GSH conjugation with dimethylmaleate (DEM) further enhanced the effects of AC on H2O 2 and O2•- formation, while N-acetylcysteine (NAC) decreased H2O2 and eliminated the enhanced generation of O2•- caused by AC. Raloxifene, which inhibits O2•- production by NAD(P)H oxidase, reduced the effects of AC on H2O2 and O2 •- production. ET increased H2O2 or O 2•- only in the presence of BSO or DEM. Conclusions: This study shows that concentrations of AC, which occur in vivo after the ingestion of alcoholic beverages, result in the formation of ROS in rat hepatic stellate cells. The increases in ROS are known to activate stellate cells promoting fibrogenesis.

Original languageEnglish (US)
Pages (from-to)1429-1435
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume30
Issue number8
DOIs
StatePublished - Aug 2006

Keywords

  • Acetaldehyde
  • Ethanol
  • Hydrogen Peroxide
  • Stellate Cells
  • Superoxide Anion

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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