Combined calcium carbimide and ethanol treatment induces high blood acetaldehyde levels, myocardial apoptosis and altered expression of apoptosis-regulating genes in rat

Alcohol Alcohol. 2002 May-Jun;37(3):222-8. doi: 10.1093/alcalc/37.3.222.

Abstract

The effects of ethanol and ethanol-derived acetaldehyde on rat myocardial apoptosis and expression of genes involved in the regulation of apoptosis and cell cycle arrest were studied. Combined ethanol and calcium carbimide treatment for 2, 5 or 8 days (E + CC) markedly increased blood acetaldehyde levels. Cytosolic DNA fragmentation was quantified in the 5-day treatment group. Increased amount of DNA-fragmentation, reflecting increased apoptosis, was evident in the E + CC group (23% increase compared to controls). mRNA levels of genes regulating apoptosis were measured by using quantitative PCR in the 2- and 8-day treatment groups. In the 2-day treatment group, p21 gene expression was increased by 25% and bax/bcl-2 mRNA ratio by 57% in E + CC, compared to the control, group. In the 8-day treatment group, p21 mRNA level was 24% lower, p53 mRNA level was 15% higher (P < 0.005), and bcl-2 mRNA level 36% higher in E + CC-treated, compared to the control, group. Interestingly, both ethanol and calcium carbimide treatments alone increased bax mRNA levels, as compared to the control group at 2 and 8 days. These results indicate that acetaldehyde might regulate the expression of apoptosis-linked genes and that apoptosis of myocardial cells may be involved in the development of alcoholic heart disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / blood*
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics*
  • Central Nervous System Depressants / pharmacology*
  • Cyanamide / pharmacology*
  • DNA Fragmentation / drug effects
  • DNA Fragmentation / physiology
  • Drug Combinations
  • Ethanol / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology
  • Male
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Rats
  • Rats, Wistar

Substances

  • Central Nervous System Depressants
  • Drug Combinations
  • Ethanol
  • Cyanamide
  • Acetaldehyde