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Alcohol and Alcoholism Vol. 37, No. 3, pp. 222-228, 2002
© 2002 Medical Council on Alcohol

COMBINED CALCIUM CARBIMIDE AND ETHANOL TREATMENT INDUCES HIGH BLOOD ACETALDEHYDE LEVELS, MYOCARDIAL APOPTOSIS AND ALTERED EXPRESSION OF APOPTOSIS-REGULATING GENES IN RAT

Heidi Jänkälä1,3, C. J. Peter Eriksson5, Kari K. Eklund2, Matti Härkönen1 and Tiina Mäki4,*

1 Department of Clinical Chemistry,
2 Division of Rheumatology and
3 Department of Psychiatry, Helsinki University Central Hospital, Haartmaninkatu 4, SF-00290 Helsinki,
4 Clinical Laboratory of Jorvi Hospital and
5 Department of Mental Health and Alcohol Research, National Public Health Institute, POB 33, SF-00251 Helsinki, Finland

Received 30 May 2001; first review notified 30 October 2001; accepted 23 November 2001

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.


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 Ther Adv Cardiovasc DisHome page
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