Chronic alcohol consumption increases the sensitivity of rat liver mitochondrial respiration to inhibition by nitric oxide
Article first published online: 30 DEC 2003
Copyright © 2003 American Association for the Study of Liver Diseases
Volume 38, Issue 1, pages 141–147, July 2003
How to Cite
Venkatraman, A., Shiva, S., Davis, A. J., Bailey, S. M., Brookes, P. S. and Darley-Usmar, V. M. (2003), Chronic alcohol consumption increases the sensitivity of rat liver mitochondrial respiration to inhibition by nitric oxide. Hepatology, 38: 141–147. doi: 10.1053/jhep.2003.50293
- Issue published online: 30 DEC 2003
- Article first published online: 30 DEC 2003
- Manuscript Accepted: 18 APR 2003
- Manuscript Received: 22 JAN 2003
- Supported by grants from NIH AA13682 (S.M.B.) and AA13395 (V.D.U.). S.S. received support from an NIH cardiovascular training grant, and P.S.B. received support from the American Heart Association and University of Alabama at Birmingham's Clinical Nutrition Research Center.
Chronic alcohol consumption is a well-known risk factor for hepatic injury, and mitochondrial damage plays a significant role in this process. Nitric oxide (NO) is an important modulator of mitochondrial function and is known to inhibit mitochondrial respiration. However, the impact of chronic alcohol consumption on NO-dependent control of liver mitochondrial function is unknown. This study examines the effect of alcohol exposure on liver mitochondria in a rat model and explores the interaction of NO and mitochondrial respiration in this context. Mitochondria were isolated from the liver of both control and ethanol-fed rats after 5 to 6 weeks of alcohol consumption. Mitochondria isolated from ethanol-treated rats showed a significant decrease in state 3 respiration and respiratory control ratio that was accompanied by an increased sensitivity to NO-dependent inhibition of respiration. In conclusion, we show that chronic alcohol consumption leads to increased sensitivity to the inhibition of respiration by NO. We propose that this results in a greater vulnerability to hypoxia and the development of alcohol-induced hepatotoxicity.