Ethanol feeding enhances age-related deterioration of the rat hepatic mitochondrion.
Chronic ethanol feeding damages the hepatic mitochondrion by increasing mitochondrial DNA (mtDNA) oxidation, lowering mtDNA yields and impairing mitochondrial respiration. These effects are also seen during aging. By employing a 21-day chronic feeding regimen, we investigated the effects of ethanol consumption on mtDNA content and mitochondrial respiration in 2-, 12-, and 24-mo-old male rats. 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 cause 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.
Cahill
Alan
A
Dept. of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. alan.cahill@jefferson.edu
Hershman
Stuart
S
Davies
Adrian
A
Sykora
Peter
P
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology; D004272:DNA, Mitochondrial / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005235:Fatty Liver, Alcoholic / Q000209:etiology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology*; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344
D004272:DNA, Mitochondrial; D000431:Ethanol; D002950:Citrate (si)-Synthase