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Mitochondrial fatty acid oxidation and susceptibility to endotoxin in acute liver injury
Abstract:
Farrar, W. Edmund, Jr. (Walter Reed Army Institute of Research, Washington, D.C.), Laurence M. Corwin, and Thomas H. Kent. Mitochondrial fatty acid oxidation and susceptibility to endotoxin in acute liver injury. J. Bacteriol. 90:1365-1372. 1965.-Acute liver injury was produced in guinea pigs with three chemically unrelated hepatotoxins: CCl(4), allyl alcohol, and dl-ethionine. The effects of these agents on liver morphology, susceptibility of animals to Escherichia coli endotoxin, endotoxin-inactivating ability of tissue homogenates, and substrate oxidation by liver mitochondria were studied. CCl(4) markedly reduced oxidation of all substrates studied except succinate, impaired the ability of liver homogenates to detoxify endotoxin in vitro, and increased the susceptibility of animals to the lethal effect of endotoxin by 150-fold. Allyl alcohol produced a severe morphological lesion in the liver but did not impair fatty acid oxidation by mitochondria, diminish endotoxin detoxification by liver homogenates, or greatly enhance susceptibility of the animals to endotoxin. Ethionine showed an effect intermediate between the other two agents. These findings are consistent with the hypothesis that the liver performs an important function in the detoxification of endotoxin by the oxidation of fatty acid residues in the endotoxin molecule.
Insights
Acute liver injury impairs the liver
Area of Science:
- Biochemistry
- Toxicology
- Microbiology
Background:
- Acute liver injury can be induced by various hepatotoxins.
- The liver plays a role in detoxifying harmful substances, including endotoxins.
- Mitochondrial function, specifically fatty acid oxidation, may be involved in liver detoxification processes.
Purpose of the Study:
- To investigate the relationship between mitochondrial fatty acid oxidation and susceptibility to endotoxin in acute liver injury.
- To determine how different hepatotoxins affect liver morphology, endotoxin detoxification, and mitochondrial function.
- To test the hypothesis that liver's endotoxin detoxification involves fatty acid oxidation.
Main Methods:
- Acute liver injury was induced in guinea pigs using carbon tetrachloride (CCl4), allyl alcohol, and dl-ethionine.
- Evaluated liver morphology, animal susceptibility to Escherichia coli endotoxin, and endotoxin-inactivating ability of tissue homogenates.
- Assessed substrate oxidation by liver mitochondria.
Main Results:
- Carbon tetrachloride (CCl4) significantly reduced mitochondrial fatty acid oxidation, impaired endotoxin detoxification, and increased endotoxin lethality 150-fold.
- Allyl alcohol caused severe liver damage but did not significantly affect fatty acid oxidation or endotoxin detoxification.
- Ethionine exhibited intermediate effects between CCl4 and allyl alcohol.
Conclusions:
- Impaired mitochondrial fatty acid oxidation in acute liver injury correlates with increased susceptibility to endotoxin.
- The liver's ability to detoxify endotoxin appears linked to its mitochondrial fatty acid oxidation capacity.
- Findings support the hypothesis that liver detoxifies endotoxin via oxidation of its fatty acid residues.