Advertisement

Carbon Tetrachloride-Induced Hepatotoxicity: A Classic Model of Lipid Peroxidation and Oxidative Stress

  • Samar BasuEmail author
Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

Carbon tetrachloride (CCl4)-induced lipid peroxidation and liver injury is a classic experimental model for comprehending the cellular mechanisms behind oxidative injury, and further estimating the therapeutic potential of drugs and antioxidants. Several methods have often been used to study free radical-induced lipid peroxidation following CCl4 induction suffer methodological discrepancies when considering the measurements in vivo, and thus the results could not be evaluated appropriately. Isoprostanes, free radical-derived prostaglandin F2-like compounds, extended a new era of determination of oxidant stress in vivo. This chapter mainly focuses on the formation of F2-isoprostanes as a marker of oxidative stress and its relation to inflammatory responses by evaluating prostaglandin F (PGF) formation following CCl4 treatment in experimental animals, and their further regulation by antioxidants. In this context, a study protocol on the induction of oxidative stress in rats is described to evaluate these eicosanoids. Both eicosanoids (F2-isoprostanes and PGF) are increased dramatically in liver tissue, peripheral plasma and urine, but with varied kinetics of formation, release and excretion patterns. Consequently, free radical- and cyclooxygenase-mediated oxidation of arachidonic acid products are closely associated with experimental hepatotoxicity, and thus could be used as consistent model of oxidative stress using a reliable in vivo marker of oxidative stress. In addition, its relation to inflammation has been further verified by applying this experimental model. Antioxidants have been shown to influence both the formation of F2-isoprostanes and prostaglandin formation, but the therapeutic values and precise mechanisms of action still remain uncertain.

Keywords

Antioxidants Carbon tetrachloride Cyclooxygenases Free ­radicals Inflammation Isoprostanes Lipid peroxidation Oxidative injury Prostaglandins 

References

  1. 1.
    Basu S (2003) Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 189: 113–127PubMedCrossRefGoogle Scholar
  2. 2.
    Hardin BL, Jr. (1954) Carbon tetrachloride poisoning; a review. Industrial medicine & surgery 23: 93–105Google Scholar
  3. 3.
    Lamson P, Wing R (1926) Early cirrhosis of the liver produced in dogs by carbon tetrachloride. J Pharmacol Exp Ther 29: 191–202Google Scholar
  4. 4.
    Bacon BR, Tavill AS, Brittenham GM, Park CH, Recknagel RO (1983) Hepatic lipid peroxidation in vivo in rats with chronic iron overload. The Journal of clinical investigation 71: 429–439PubMedCrossRefGoogle Scholar
  5. 5.
    Comporti M (1985) Lipid peroxidation and cellular damage in toxic liver injury. Laboratory investigation; a journal of technical methods and pathology 53: 599–623Google Scholar
  6. 6.
    Brattin WJ, Glende EA, Jr., Recknagel RO (1985) Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radic Biol Med 1: 27–38PubMedCrossRefGoogle Scholar
  7. 7.
    Basu S (1999) Oxidative injury induced cyclooxygenase activation in experimental hepatotoxicity. Biochemical and biophysical research communications 254: 764–767PubMedCrossRefGoogle Scholar
  8. 8.
    Basu S (2004) Isoprostanes: novel bioactive products of lipid peroxidation. Free radical research 38: 105–122PubMedCrossRefGoogle Scholar
  9. 9.
    Basu S (2007) Novel cyclooxygenase-catalyzed bioactive prostaglandin F(2alpha) from physiology to new principles in inflammation. Medicinal research reviews 27: 435–468PubMedCrossRefGoogle Scholar
  10. 10.
    Morrow JD, Awad JA, Kato T, et al. (1992) Formation of novel non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in carbon tetrachloride hepatotoxicity. An animal model of lipid peroxidation. The Journal of clinical investigation 90: 2502–2507PubMedCrossRefGoogle Scholar
  11. 11.
    Morrow JD, Harris TM, Roberts LJ, 2nd (1990) Noncyclooxygenase oxidative formation of a series of novel prostaglandins: analytical ramifications for measurement of eicosanoids. Analytical biochemistry 184: 1–10PubMedCrossRefGoogle Scholar
  12. 12.
    Sodergren E, Cederberg J, Vessby B, Basu S (2001) Vitamin E reduces lipid peroxidation in experimental hepatotoxicity in rats. European journal of nutrition 40: 10–16PubMedCrossRefGoogle Scholar
  13. 13.
    Riely CA, Cohen G, Lieberman M (1974) Ethane evolution: a new index of lipid peroxidation. Science (New York, NY) 183: 208–210Google Scholar
  14. 14.
    Dillard CJ, Dumelin EE, Tappel AL (1977) Effect of dietary vitamin E on expiration of pentane and ethane by the rat. Lipids 12: 109–114PubMedCrossRefGoogle Scholar
  15. 15.
    Hafeman DG, Hoekstra WG (1977) Protection against carbon tetrachloride-induced lipid peroxidation in the rat by dietary vitamin E, selenium, and methionine as measured by ethane evolution. The Journal of nutrition 107: 656  –  665PubMedGoogle Scholar
  16. 16.
    Wolff S (1994) Ferros iso oxidation in presence of ferric ion indicator xyloenol orange for measurement of hydroperoxide. Methods in enzymology 233: 183–189CrossRefGoogle Scholar
  17. 17.
    Marshall PJ, Warso MA, Lands WE (1985) Selective microdetermination of lipid hydroperoxides. Analytical biochemistry 145: 192–199PubMedCrossRefGoogle Scholar
  18. 18.
    Hicks M, Gebicki JM (1979) A spectrophotometric method for the determination of lipid hydroperoxides. Analytical biochemistry 99: 249–253PubMedCrossRefGoogle Scholar
  19. 19.
    Esterbauer H, Striegl G, Puhl H, Rotheneder M (1989) Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun 6: 67–75PubMedCrossRefGoogle Scholar
  20. 20.
    Dormandy TL, Wickens DG (1987) The experimental and clinical pathology of diene conjugation. Chemistry and physics of lipids 45: 353–364PubMedCrossRefGoogle Scholar
  21. 21.
    Corongiu FP, Banni S (1994) Detection of conjugated dienes by second derivative ultraviolet spectrophotometry. Methods in enzymology 233: 303–310PubMedCrossRefGoogle Scholar
  22. 22.
    Ottolenghi A (1959) 2-Thiobarbituric acid (TBA) method. Arch Biochem Biophys 77: 355–359CrossRefGoogle Scholar
  23. 23.
    Mihara M, Uchiyama M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Analytical biochemistry 86: 271–278PubMedCrossRefGoogle Scholar
  24. 24.
    Bird RP, Hung SS, Hadley M, Draper HH (1983) Determination of malonaldehyde in biological materials by high-pressure liquid chromatography. Analytical biochemistry 128: 240–244PubMedCrossRefGoogle Scholar
  25. 25.
    Young IS, Trimble ER (1991) Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection. Annals of clinical biochemistry 28 (Pt 5): 504–508PubMedGoogle Scholar
  26. 26.
    Gutteridge JM, Halliwell B (1990) The measurement and mechanism of lipid peroxidation in biological systems. Trends Biochem Sci 15: 129–135PubMedCrossRefGoogle Scholar
  27. 27.
    Halliwell B, Grootveld M (1987) The measurement of free radical reactions in humans. Some thoughts for future experimentation. FEBS Lett 213: 9–14PubMedCrossRefGoogle Scholar
  28. 28.
    Morrow JD, Awad JA, Boss HJ, Blair IA, Roberts LJ, 2nd (1992) Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids. Proceedings of the National Academy of Sciences of the United States of America 89: 10721–10725PubMedCrossRefGoogle Scholar
  29. 29.
    Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJd (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proceedings of the National Academy of Sciences of the United States of America 87: 9383–9387PubMedCrossRefGoogle Scholar
  30. 30.
    Kadiiska MB, Gladen BC, Baird DD, et al. (2005) Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free radical biology & medicine 38: 698–710CrossRefGoogle Scholar
  31. 31.
    Kadiiska MB, Gladen BC, Baird DD, et al. (2005) Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning. Free radical biology & medicine 38: 711–718CrossRefGoogle Scholar
  32. 32.
    Basu S (2008) F2-Isoprostanes in human health and diseases: From molecular mechanisms to clinical implications Antioxidant & Redox Signaling 10: 1405–1434Google Scholar
  33. 33.
    Basu S (2007) The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target. Scandinavian Journal of Food and Nutrition 51: 48–61CrossRefGoogle Scholar
  34. 34.
    Morrow JD, Roberts LJ, 2nd (1996) The isoprostanes. Current knowledge and directions for future research. Biochemical pharmacology 51: 1–9PubMedCrossRefGoogle Scholar
  35. 35.
    Lawson JA, Rokach J, FitzGerald GA (1999) Isoprostanes: formation, analysis and use as indices of lipid peroxidation in vivo. The Journal of biological chemistry 274: 24441–24444PubMedCrossRefGoogle Scholar
  36. 36.
    Casadesus G, Smith MA, Basu S, et al. (2007) Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease. Molecular neurodegeneration 2: 2PubMedCrossRefGoogle Scholar
  37. 37.
    Jonasson S, Hjoberg J, Hedenstierna G, Basu S (2009) Allergen-induced formation of F2-isoprostanes in a murine asthma model identifies oxidative stress in acute airway ­inflammation in vivo. Prostaglandins, leukotrienes, and essential fatty acids 80: 1–7PubMedCrossRefGoogle Scholar
  38. 38.
    Sodergren E, Vessby B, Basu S (2000) Radioimmunological measurement of F(2)-isoprostanes after hydrolysis of lipids in tissues. Prostaglandins, leukotrienes, and essential fatty acids 63: 149–152PubMedCrossRefGoogle Scholar
  39. 39.
    Samuelsson B, Goldyne M, Granstrom E, Hamberg M, Hammarstrom S, Malmsten C (1978) Prostaglandins and thromboxanes. Annu Rev Biochem 47: 997–1029PubMedCrossRefGoogle Scholar
  40. 40.
    Kuehl FA, Jr., Humes JL, Egan RW, Ham EA, Beveridge GC, Van Arman CG (1977) Role of prostaglandin endoperoxide PGG2 in inflammatory processes. Nature 265: 170–173PubMedCrossRefGoogle Scholar
  41. 41.
    Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 231: 232–235PubMedGoogle Scholar
  42. 42.
    Basu S (1998) Radioimmunoassay of 8-iso-prostaglandin F2alpha: an index for oxidative injury via free radical catalysed lipid peroxidation. Prostaglandins, leukotrienes, and essential fatty acids 58: 319–325PubMedCrossRefGoogle Scholar
  43. 43.
    Recknagel RO (1967) Carbon tetrachloride hepatotoxicity. Pharmacol Rev 19: 145–208PubMedGoogle Scholar
  44. 44.
    Recknagel RO, Glende EA, Jr., Dolak JA, Waller RL (1989) Mechanisms of carbon ­tetrachloride toxicity. Pharmacol Ther 43: 139–154PubMedCrossRefGoogle Scholar
  45. 45.
    Rubin E, Popper H (1967) The evolution of human cirrhosis deduced from observations in experimental animals. Medicine (Baltimore) 46: 163–183CrossRefGoogle Scholar
  46. 46.
    Castro JA, Gomez MI (1972) Studies on the irreversible binding of 14 C-CCl 4 to microsomal lipids in rats under varying experimental conditions. Toxicology and applied pharmacology 23: 541–552PubMedCrossRefGoogle Scholar
  47. 47.
    Diaz Gomez MI, Castro JA (1973) Effect of inhibitors of drug metabolism on mitochondrial swelling and on carbon tetrachloride-induced lysosomal damage. Toxicology and applied pharmacology 24: 378–386PubMedCrossRefGoogle Scholar
  48. 48.
    Comporti M, Saccocci C, Dianzani MU (1965) Effect of CCl-4 in vitro and in vivo on lipid peroxidation of rat liver homogenates and subcellular fractions. Enzymologia 29: 185–204PubMedGoogle Scholar
  49. 49.
    Ghoshal AK, Recknagel RO (1965) Positive Evidence of Acceleration of Lipoperoxidation in Rat Liver by Carbon Tetrachloride: In Vitro Experiments. Life sciences 4: 1521–1530PubMedCrossRefGoogle Scholar
  50. 50.
    Ingail A, Lott, K. and Slater, TF (1978) Metabolic activation of carbon tetrachloride to a ­free-radical products: Studies using a spin trap. Biochem Soc Trans 6: 962–978Google Scholar
  51. 51.
    McCay PB, Lai EK, Poyer JL, DuBose CM, Janzen EG (1984) Oxygen- and carbon-centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro. The Journal of biological chemistry 259: 2135–2143PubMedGoogle Scholar
  52. 52.
    Noguchi T, Fong KL, Lai EK, et al. (1982) Specificity of a phenobarbital-induced cytochrome P-450 for metabolism of carbon tetrachloride to the trichloromethyl radical. Biochemical pharmacology 31: 615–624PubMedCrossRefGoogle Scholar
  53. 53.
    Poyer JL, McCay PB, Lai EK, Janzen EG, Davis ER (1980) Confirmation of assignment of the trichloromethyl radical spin adduct detected by spin trapping during 13C-carbon tetrachloride metabolism in vitro and in vivo. Biochemical and biophysical research communications 94: 1154–1160PubMedCrossRefGoogle Scholar
  54. 54.
    Packer J, Slater, TF and Willson, R.L. (1978) Reactions of carbontetrachloride-related peroxy free radical (CCl3.O2) with amino acids. Pulse radiolysis evidence. Life sciences 23: 365–362CrossRefGoogle Scholar
  55. 55.
    Morrow JD, Tapper AR, Zackert WE, et al. (1999) Formation of novel isoprostane-like compounds from docosahexaenoic acid. Advances in experimental medicine and biology 469: 343–347PubMedCrossRefGoogle Scholar
  56. 56.
    Basu S (1998) Metabolism of 8-iso-prostaglandin F2alpha. FEBS Lett 428: 32–36PubMedCrossRefGoogle Scholar
  57. 57.
    Glende EA, Jr., Recknagel RO (1969) Biochemical basis for the in vitro pro-oxidant action of carbon tetrachloride. Experimental and molecular pathology 11: 172–185PubMedCrossRefGoogle Scholar
  58. 58.
    Gonzalez Padron A, de Toranzo EG, Castro JA (1996) Depression of liver microsomal glucose 6-phosphatase activity in carbon tetrachloride-poisoned rats. Potential synergistic effects of lipid peroxidation and of covalent binding of haloalkane-derived free radicals to cellular components in the process. Free radical biology & medicine 21: 81–87CrossRefGoogle Scholar
  59. 59.
    Blazka ME, Wilmer JL, Holladay SD, Wilson RE, Luster MI (1995) Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicology and applied pharmacology 133: 43–52PubMedCrossRefGoogle Scholar
  60. 60.
    Bruccoleri A, Gallucci R, Germolec DR, et al. (1997) Induction of early-immediate genes by tumor necrosis factor alpha contribute to liver repair following chemical-induced hepatotoxicity. Hepatology 25: 133–141PubMedCrossRefGoogle Scholar
  61. 61.
    Luster MI, Simeonova PP, Gallucci RM, Bruccoleri A, Blazka ME, Yucesoy B (2001) Role of inflammation in chemical-induced hepatotoxicity. Toxicology letters 120: 317–321PubMedCrossRefGoogle Scholar
  62. 62.
    Tappel AL (1980) Vitamin E and selenium protection from in vivo lipid peroxidation. Annals of the New York Academy of Sciences 355: 18–31PubMedCrossRefGoogle Scholar
  63. 63.
    Kunert KJ, Tappel AL (1983) The effect of vitamin C on in vivo lipid peroxidation in guinea pigs as measured by pentane and ethane production. Lipids 18: 271–274PubMedCrossRefGoogle Scholar
  64. 64.
    Knook DL, Bosma A, Seifert WF (1995) Role of vitamin A in liver fibrosis. Journal of gastroenterology and hepatology 10 Suppl 1: S47–49PubMedCrossRefGoogle Scholar
  65. 65.
    Seifert WF, Bosma A, Hendriks HF, et al. (1995) Beta-carotene (provitamin A) decreases the severity of CCl4-induced hepatic inflammation and fibrosis in rats. Liver 15: 1–8PubMedCrossRefGoogle Scholar
  66. 66.
    Merino N, Gonzalez R, Gonzalez A, Remirez D (1996) Histopathological evaluation on the effect of red propolis on liver damage induced by CCl4 in rats. Arch Med Res 27: 285–289PubMedGoogle Scholar
  67. 67.
    Iyama T, Takasuga A, Azuma M (1996) beta-Carotene accumulation in mouse tissues and a protective role against lipid peroxidation. International journal for vitamin and nutrition research Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung 66: 301–305Google Scholar
  68. 68.
    Burton GW, Ingold KU (1989) Vitamin E as an in vitro and in vivo antioxidant. Annals of the New York Academy of Sciences 570: 7–22PubMedCrossRefGoogle Scholar
  69. 69.
    Gutteridge JM, Halliwell B (2000) Free radicals and antioxidants in the year 2000. A historical look to the future. Annals of the New York Academy of Sciences 899: 136–147PubMedCrossRefGoogle Scholar
  70. 70.
    Halliwell B (1990) How to characterize a biological antioxidant. Free Radic Res Commun 9: 1–32PubMedCrossRefGoogle Scholar
  71. 71.
    Halliwell B (2000) Lipid peroxidation, antioxidants and cardiovascular disease: how should we move forward? Cardiovasc Res 47: 410  –  418PubMedCrossRefGoogle Scholar
  72. 72.
    Lieber CS, DeCarli LM, Mak KM, Kim CI, Leo MA (1990) Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. Hepatology 12: 1390–1398PubMedCrossRefGoogle Scholar
  73. 73.
    Lieber CS, Robins SJ, Li J, et al. (1994) Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology 106: 152–159PubMedGoogle Scholar
  74. 74.
    Ma X, Zhao J, Lieber CS (1996) Polyenylphosphatidylcholine attenuates non-alcoholic hepatic fibrosis and accelerates its regression. J Hepatol 24: 604–613PubMedCrossRefGoogle Scholar
  75. 75.
    Aleynik SI, Leo MA, Aleynik MK, Lieber CS (1998) Increased circulating products of lipid peroxidation in patients with alcoholic liver disease. Alcohol Clin Exp Res 22: 192–196PubMedCrossRefGoogle Scholar
  76. 76.
    Awad JA, Morrow JD, Hill KE, Roberts LJ, 2nd, Burk RF (1994) Detection and localization of lipid peroxidation in selenium- and vitamin E-deficient rats using F2-isoprostanes. The Journal of nutrition 124: 810–816PubMedGoogle Scholar
  77. 77.
    Smedman A, Vessby B, Basu S (2004) Isomer-specific effects of conjugated linoleic acid on lipid peroxidation in humans: regulation by alpha-tocopherol and cyclo-oxygenase-2 inhibitor. Clin Sci (Lond) 106: 67–73CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Laboratorie de Biochimie, Biologie Moléculaire et Nutrition, Faculté de PharmacieUniversité d’AuvergneClermont-FerrandFrance
  2. 2.Oxidative stress and Inflammation, Department of Public Health and Caring Sciences, Faculty of MedicineUppsala UniversityUppsalaSweden

Personalised recommendations