Submitted on April 29, 2005
Accepted on June 27, 2005
Ethanol feeding enhances age-related deterioration of the rat hepatic mitochondrion
Alan Cahill1*, Stuart Hershman1, Adrian Davies1, and Peter Sykora1
1 Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
* To whom correspondence should be addressed. E-mail: alan.cahill{at}jefferson.edu.
Background and rationale: chronic ethanol feeding damages the hepatic mitochondrion
by increasing mtDNA oxidation, lowering mtDNA yields and impairing mitochondrial
respiration. These effects are also seen during aging. Employing a 21-day chronic
feeding regimen, we investigated the effects of ethanol consumption upon mtDNA
content and mitochondrial respiration in 2, 12 and 24 month old male rats. Results:
Aging resulted in decreased mtDNA content, increased mtDNA damage as indicated by
inhibition of Taq polymerase progression, and a decline in state 3 respiration; effects that
were further exacerbated by ethanol feeding. Additionally, ethanol consumption caused
an increase in the levels of citrate synthase while not impacting mitochondrial protein
content. In conclusion: ethanol and aging combine to causes deterioration in the
structural and functional integrity of the hepatic mitochondrion. The additive effects of
aging and ethanol feeding may have serious consequences for hepatic energy metabolism
in aged animals and their detrimental combination may serve as one of the molecular
mechanisms underlying the progression of alcoholic liver disease.
