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Research ArticleArticle

The Role of Lipid Peroxidation in the Pathogenesis of Carbon Tetrachloride-Induced Liver Injury

DAVID H. ALPERS, MICHAEL SOLIN and KURT J. ISSELBACHER
Molecular Pharmacology November 1968, 4 (6) 566-573;
DAVID H. ALPERS
Department of Medicine, Harvard Medical School, and the Medical Services (Gastrointestinal Unit), Massachusetts General Hospital, Boston, Massachusetts 02114
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MICHAEL SOLIN
Department of Medicine, Harvard Medical School, and the Medical Services (Gastrointestinal Unit), Massachusetts General Hospital, Boston, Massachusetts 02114
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KURT J. ISSELBACHER
Department of Medicine, Harvard Medical School, and the Medical Services (Gastrointestinal Unit), Massachusetts General Hospital, Boston, Massachusetts 02114
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Abstract

The effect of carbon tetrachloride on lipid peroxidation and protein synthesis has been studied in rat liver. In liver microsomes, no correlation could be found in vitro between the degree of lipid peroxidation and protein synthesis. Stimulation of peroxidation by CCl4, ultraviolet irradiation, or ascorbic acid, or inhibition of peroxidation by vitamin K, did not affect the rate of protein synthesis. Despite large changes in the degree of lipid peroxidation in vitro, ribosomes remained bound to microsomal membranes.

The administration of antioxidant in vivo, such as N,N’-diphenyl-p-phenylenediamine or α-tocopherol, prevented the fatty liver and necrosis produced by CCl4, but did not reverse the inhibition of protein synthesis in liver slices or isolated polyribosomes derived from such animals. Since the formation and release of hepatic hipoproteins involve many steps, including triglyceride synthesis, interaction with apoprotein, and release or secretion of lipoprotein from the liver, it is possible that antioxidants act at some stage other than apoprotein synthesis per se.

It is concluded that the demonstration of lipid peroxidation in vitro may not always imply functional damage to the subcellular component so oxidized. In particular, while CCl4 administered in vivo clearly decreases protein synthesis, there may not be a direct relationship between this effect and the degree of lipid peroxidation.

ACKNOWLEDGMENT We are indebted to Mrs. Katherine Porter for excellent technical assistance.

  • Copyright ©, 1968, by Academic Press Inc.

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Molecular Pharmacology
Vol. 4, Issue 6
1 Nov 1968
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Research ArticleArticle

The Role of Lipid Peroxidation in the Pathogenesis of Carbon Tetrachloride-Induced Liver Injury

DAVID H. ALPERS, MICHAEL SOLIN and KURT J. ISSELBACHER
Molecular Pharmacology November 1, 1968, 4 (6) 566-573;

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Research ArticleArticle

The Role of Lipid Peroxidation in the Pathogenesis of Carbon Tetrachloride-Induced Liver Injury

DAVID H. ALPERS, MICHAEL SOLIN and KURT J. ISSELBACHER
Molecular Pharmacology November 1, 1968, 4 (6) 566-573;
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