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

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


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.


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


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© 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

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