Vitamin E dietary supplementation protects against carbon tetrachloride—induced chronic liver damage and cirrhosis

Previous studies have shown that α‐tocopherol (vitamin E) pretreatment of experimental animals can protect against acute liver necrosis induced by carbon tetrachloride. In this study we investigated whether the increase of vitamin E liver content by dietary supplementation influences chronic liver damage and cirrhosis induced by carbon tetrachloride in the rat. Our data indicate that vitamin E supplementation did not interfere with the growth rate of the animals and increased about threefold the liver's content of the vitamin. Vitamin E supplementation significantly reduced oxidative liver damage, but it was not effective in protecting against development of fatty liver and did not interfere with metabolic activation of carbon tetrachloride. Moreover, vitamin E—fed animals showed incomplete but significant prevention of liver necrosis and cirrhosis induced by carbon tetrachloride. This has been shown by means of histological examination, analysis of serum parameters and biochemical evaluation of collagen content. These results show that an increased liver content of vitamin E can afford a significant degree of protection against carbon tetrachloride–induced chronic liver damage and cirrhosis. (HEPATOLOGY 1992;16:1014–1021)

[1]  R. Sokol,et al.  Effect of dietary lipid and vitamin E on mitochondrial lipid peroxidation and hepatic injury in the bile duct-ligated rat. , 1991, Journal of lipid research.

[2]  D. Brenner,et al.  d-alpha-tocopherol inhibits collagen alpha 1(I) gene expression in cultured human fibroblasts. Modulation of constitutive collagen gene expression by lipid peroxidation. , 1991, The Journal of clinical investigation.

[3]  Gressner Am Liver fibrosis: perspectives in pathobiochemical research and clinical outlook. , 1991 .

[4]  G. Poli,et al.  In vivo and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride , 1991, Cell biochemistry and function.

[5]  M. Horwitt Data supporting supplementation of humans with vitamin E. , 1991, The Journal of nutrition.

[6]  D. J. Reed,et al.  Modification of hepatic vitamin E stores in vivo. I. Alterations in plasma and liver vitamin E content by methyl ethyl ketone peroxide. , 1991, Archives of biochemistry and biophysics.

[7]  K. Minakata,et al.  Effects of vitamin E on toxicity by minute amounts of paraquat fed continuously to rats. , 1991, Journal of nutritional science and vitaminology.

[8]  M. Zern,et al.  Two rat models of hepatic fibrosis. A morphologic and molecular comparison. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[9]  S. Thorgeirsson,et al.  Transforming growth factor-beta 1 and type I procollagen transcripts during regeneration and early fibrosis of rat liver. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[10]  P. Muriel,et al.  The role of membrane composition in ATPase activities of cirrhotic rat liver: Effect of silymarin , 1990, Journal of applied toxicology : JAT.

[11]  T. Speroff,et al.  Prevention of hepatocyte injury and lipid peroxidation by iron chelators and α‐tocopherol in isolated iron‐loaded rat hepatocytes , 1990, Hepatology.

[12]  A. Gressner,et al.  Transformed fat storing cells inhibit the proliferation of cultured hepatocytes by secretion of transforming growth factor beta. , 1990, Journal of hepatology.

[13]  H. Esterbauer,et al.  Effect of 4-hydroxylalkenals on hepatic phosphatidylinositol-4,5-bisphosphate-phospholipase C. , 1990, Biochemical pharmacology.

[14]  A. Casini,et al.  Lipid peroxidation and antioxidant systems in the liver injury produced by glutathione depleting agents. , 1990, Biochemical pharmacology.

[15]  G. Poli,et al.  Comparative evaluation of the antioxidant activity of α-tocopherol, α-tocopherol polyethylene glycol 1000 succinate and α-tocopherol succinate in isolated hepatocytes and liver microsomal suspensions , 1990 .

[16]  J. Gordon,et al.  Retinoids affect collagen synthesis through inhibition of ascorbate-induced lipid peroxidation in cultured human dermal fibroblasts. , 1990, Archives of biochemistry and biophysics.

[17]  S. Friedman,et al.  Connective tissue biology and hepatic fibrosis: Report of a conference , 1990, Hepatology.

[18]  J. Seyer,et al.  Regulation of TGFβ gene expression in rat liver intoxicated with carbon tetrachloride , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  G. Poli,et al.  Lipid peroxidation and covalent binding in the early functional impairment of liver golgi apparatus by carbon tetrachloride , 1990, Cell biochemistry and function.

[20]  B. Bacon,et al.  The pathology of hepatic iron overload: A free radical‐Mediated Process? , 1990, Hepatology.

[21]  G. Bellomo,et al.  Effects of carbon tetrachloride on calcium homeostasis. A critical reconsideration. , 1989, Biochemical pharmacology.

[22]  H. Stein,et al.  In situ hybridization for procollagen types I, III and IV mRNA in normal and fibrotic rat liver: Evidence for predominant expression in nonparenchymal liver cells , 1989, Hepatology.

[23]  P. Muriel,et al.  PREVENTION OF CCL4‐INDUCED LIVER CIRRHOSIS BY SILYMARIN , 1989, Fundamental & clinical pharmacology.

[24]  L. Ala‐Kokko,et al.  Preventive effect of malotilate on dimethylnitrosamine-induced liver fibrosis in the rat. , 1989, The Journal of laboratory and clinical medicine.

[25]  G. Poli,et al.  The role of lipid peroxidation in liver damage. , 1987, Chemistry and physics of lipids.

[26]  G. Cecchini,et al.  Chemotactic activity of the lipid peroxidation product 4-hydroxynonenal and homologous hydroxyalkenals. , 1986, Biological chemistry Hoppe-Seyler.

[27]  S. Friedman,et al.  Hepatic lipocytes: the principal collagen-producing cells of normal rat liver. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Comporti Lipid peroxidation and cellular damage in toxic liver injury. , 1985, Laboratory investigation; a journal of technical methods and pathology.

[29]  G. Bellomo,et al.  Mechanisms responsible for carbon tetrachloride‐induced perturbation of mitochondrial calcium homeostasis , 1985, FEBS letters.

[30]  G. Poli,et al.  Separation and characterization of the aldehydic products of lipid peroxidation stimulated by carbon tetrachloride or ADP-iron in isolated rat hepatocytes and rat liver microsomal suspensions. , 1985, The Biochemical journal.

[31]  A. Casini,et al.  Liver glutathione depletion induced by bromobenzene, iodobenzene, and diethylmaleate poisoning and its relation to lipid peroxidation and necrosis. , 1985, The American journal of pathology.

[32]  A. Stier,et al.  Spin-trapping studies on the free-radical products formed by metabolic activation of carbon tetrachloride in rat liver microsomal fractions isolated hepatocytes and in vivo in the rat. , 1982, The Biochemical journal.

[33]  D. J. Reed,et al.  High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides. , 1980, Analytical biochemistry.

[34]  M. Rojkind,et al.  Liver proline oxidase activity and collagen synthesis in rats with cirrhosis induced by carbon tetrachloride. , 1980, Biochimica et biophysica acta.

[35]  R. Burk,et al.  Ethane production and liver necrosis in rats after administration of drugs and other chemicals. , 1979, Toxicology and applied pharmacology.

[36]  R. Zender Analyse de l'hydroxyproline urinaire. Méthode et valeurs fréquentes , 1972 .

[37]  Larry Johnson Connective Tissue , 1924, Definitions.

[38]  H. Esterbauer,et al.  Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. , 1991, Free radical biology & medicine.

[39]  C. Drevon Absorption, transport and metabolism of vitamin E. , 1991, Free radical research communications.

[40]  A. Gressner Liver fibrosis: perspectives in pathobiochemical research and clinical outlook. , 1991, European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies.

[41]  M. Fariss Oxygen toxicity: unique cytoprotective properties of vitamin E succinate in hepatocytes. , 1990, Free radical biology & medicine.

[42]  E. Albano,et al.  Inhibition of the high affinity Ca2(+)-ATPase activity in rat liver plasma membranes following carbon tetrachloride intoxication. , 1990, Chemico-biological interactions.

[43]  G. Poli,et al.  Comparative evaluation of the antioxidant activity of alpha-tocopherol, alpha-tocopherol polyethylene glycol 1000 succinate and alpha-tocopherol succinate in isolated hepatocytes and liver microsomal suspensions. , 1990, Biochemical pharmacology.

[44]  E. Wisse,et al.  Cell population kinetics of Kupffer cells during the onset of fibrosis in rat liver by chronic carbon tetrachloride administration. , 1988, Journal of hepatology.

[45]  T. Slater,et al.  Effects of α-Tocopherol on Carbon Tetrachloride Metabolism in Rat Liver Microsomes , 1987 .

[46]  G. Poli,et al.  Electron spin resonance studies on isolated hepatocytes treated with ferrous or ferric iron. , 1987, Free radical research communications.

[47]  T. Slater,et al.  Effects of alpha-tocopherol on carbon tetrachloride metabolism in rat liver microsomes. , 1987, Free radical research communications.

[48]  M. Dianzani,et al.  Effects of 4-hydroxynonenal on adenylate cyclase and 5'-nucleotidase activities in rat liver plasma membranes. , 1985, Chemico-biological interactions.

[49]  W. Brattin,et al.  Pathological mechanisms in carbon tetrachloride hepatotoxicity. , 1985, Journal of free radicals in biology & medicine.

[50]  T. Slater Free-radical mechanisms in tissue injury. , 1984, The Biochemical journal.