Effects of Ethanol and Fat on the Transport of Reducing Equivalents into Rat Liver Mitochondria (original) (raw)
Related papers
Chronic low dose ethanol intake: Biochemical characterization of liver mitochondria in rats
Life Sciences, 2000
Liver mitochondria were isolated from male rats exposed for 2 months to low doses of ethanol (3% v/v in drinking water), a condition not associated with tolerance or dependence. The results show no significant changes in the content of reduced or oxidized glutathione in the liver mitochondria of ethanol treated rats with respect to controls. However, a slight but significant increase in lipid peroxidation, accompanied by an increased content of oxidized proteins, was found in el.hanol exposed animals. Mitochondrial content of cytochrome complexes was not significantly affected by ethanol intake. The specific enzymatic activity of cytochrome oxidase showed, however, a . significant decrease in ethanol-treated rats. The slight mitochondrial alterations found in the liver of rats exposed chronically to low doses of ethanol might represent the beginning of a more extensive damage previously observed in rats exposed to high doses of this substance.
Biochemical Pharmacology, 1978
Incorporation in vitro of labeled leucine into isolated rat liver mitochondria was decreased in animals chronically fed ethanol. To avoid artifactual leucine incorporation, no trichloroacetic acid (TCA) precipitation was performed. Further, it was found that when these mitochondrial proteins were separated on sodium dodecyl sulfate polyacrylamide gels, no specific reduction of leucine incorporation into any indi~dua1 protein bands could be detected. This probably reflected a general decrease in amino acid incorporation occurring in these isolated mitochondria. Incorporation in uiuo of labeled arginine detected a decrease in the viability of rat liver mitochondria from chronic ethanol-fed rats. This incorporation revealed a 2&y decrease in the half-life of liver mitochondria from chronic ethanolfed rats. It was also found that arginine incorporation by the cytoplasmic protein-synthesizing system is increased in uivo after chronic ethanol feeding. The results from these experiments suggest that if this reaction were to persist through continuous consumption of ethanol, there would in time be diminished amounts of properly assembled proteins which are necessary for membrane structure and function. Whether or not such induced deficiencies in the mitochondria over a long period of time
Role of mitochondria in hepatotoxicity of ethanol
Biophysics, 2010
The current understanding of the effects of alcohol intoxication on the basic mitochondrial func tions has been presented. Both, the direct toxic effect of ethanol on biological membranes and various cellular systems and the toxicity of acetaldehyde and reactive oxygen species (the products of ethanol oxidation) are discussed, with emphasis on the effect of ethanol on the basic functions of mitochondria and Ca 2+ dependent mitochondrial permeability transition. Based on the available experimental data, it is demonstrated that acute alcohol intoxication causes a global mitochondrial dysfunction in the liver, resulting in considerable distur bance of the whole cellular metabolism. Alcohol poisoning of the liver leads to a decreased ability of cells to withstand oxidative stress, to support the synthesis of vital metabolic intermediates (e.g., methyl groups), as well as to produce urea from ammonia, due to a decreased permeability of the outer membrane and impaired exchange of substrates between the cytoplasm and the mitochondrial matrix. This review emphasizes the role of porin channels of the outer mitochondrial membrane in ethanol mediated disturbances of basic mito chondrial functions and its consequences for the entire cell metabolism in the liver.
Journal of Clinical Investigation, 1994
Chronic ethanol feeding selectively impairs the translocation of cytosol GSH into the mitochondrial matrix. Since ethanol-induced liver cell injury is preferentially localized in the centrilobular area, we examined the hepatic acinar distribution of mitochondrial GSH transport in ethanol-fed rats. Enriched periportal (PP) and perivenous (PV) hepatocytes from pairand ethanol-fed rats were prepared as well as mitochondria from these cells. The mitochondrial pool size of GSH was decreased in both PP and PV cells from ethanol-fed rats either as expressed per 106 cells or per microliter of mitochondrial matrix volume. The rate of reaccumulation of mitochondrial GSH and the linear relationship of mitochondrial to cytosol GSH from ethanol-fed mitochondria were lower for both PP and PV cells, effects observed more prominently in the PV cells. Mitochondrial functional integrity was lower in both PP and PV ethanol-fed rats, which was associated with decreased cellular ATP levels and mitochondrial membrane potential, effects which were greater in the PV cells. Mitochondrial GSH depletion by ethanol feeding preceded the onset of functional changes in mitochondria, suggesting that mitochondrial GSH is critical in maintaining a functionally competent organelle and that the greater depletion of mitochondrial GSH by ethanol feeding in PV cells could contribute to the pathogenesis of alcoholic liver disease. (J. Clin. Invest. 1994. 94:193-201.)
Mitochondrial remodeling in the liver following chronic alcohol feeding to rats
Free radical biology & medicine, 2017
The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to cause declines in mitochondrial respiration (state III), decreased expression of respiratory complexes, and decreased respiratory control ratios (RCR) in liver mitochondria. These declines and other mitochondrial alterations have led to the hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver. If oral alcohol feeding leads to mitochondrial dysfunction, one would predict that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats would cause greater declines in mitochondrial bioenergetics in the liver. In this study, we examined the mitochondrial alterations that occur in rats fed alcohol both orally and intragastrically. Oral alcohol feeding decreased glutamate/malate-, acetaldehyde- and succinate-driven state III respiration, RCR, and expression of respiratory complexes (I, III, IV, V) in liver mitochondria, in agreement with previous results. IG alco...
FEBS letters, 2000
The efficiency of oxidative phosphorylation was compared between rats chronically fed with ethanol and controls. (i) Results showed that the liver mitochondria state 4 respiratory rate was strongly inhibited, while the corresponding protonmotive force was not affected; (ii) the cytochrome oxidase content and activity were decreased and (iii) the oxidativephosphorylation yield was increased in the ethanol exposed group. Furthermore, oxidative phosphorylation at coupling site II was not affected by ethanol. Cytochrome oxidase inhibition by sodium-azide mimicked the effects of ethanol intoxication in control mitochondria. This indicates that the decrease in cytochrome oxidase activity induced by ethanol intoxication directly increases the efficiency of oxidative phosphorylation.