Carbon tetrachloride lipid peroxidation

Poli, G., Dianzani, M.U., Cheeseman, K.H., Slater, T.F., Lang, J. and Esterbauer, H. (1985). 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. Biochem. J. 227, 629-638,... 

Castillo, T., Koop, D.R., Kamimura, S., Triadafilopoulos, G. and Tsukamoto, H. (1992). Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron-dependent microsomal lipid peroxidation. Hepatology 16, 992-996. 

Biasi, F., Albano, E., Chiarpotto, E., Corongju, F.P., Pron-zato, M.A., Marinari, U. M., Parola, M., Dianzani, M.U. and Poli, G. (1991). Invivo and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride. Cell Biochem. Function 9, 111-118. 

Comporti, M., Saccocci, C. and Dianzani, M.U. (1965). EfiFect of carbon tetrachloride in vitro and in vivo on lipid peroxidation of rat liver homogenates and subcellular fractions. Enzymologja 29, 185-204. 

Corongiu, F.P., Lai, M. and Milia, A. (1983). Carbon tetrachloride, bromotrichloromethane and ethanol acute intoxication. New chemical evidence for lipid peroxidation in rat tissue microsomes. Biochem. J. 212, 625-631. 

ElSisi, A.E.D., Earnest, D.L. and Sipes, LG. (1993a). Vitamin-A potentiation of carbon tetrachloride hepatotoxicity -enhanced lipid peroxidation without enhanced biotransformation. Toxicol. Appl. Pharmacol. 119, 289-294. 

Le Page, KN., Cheeseman, K.H., Osman, N. and Slater, T.F. (1988). Lipid peroxidation in purified plasma membrane fractions of rat liver in relation to the toxicity of carbon tetrachloride. Cell Biochem. Function 6, 87-99. 

Recknagel, R.O. and Ghoshal, A.K. (1966). Lipid peroxidation as a vector in carbon tetrachloride hepatotoxicity. Lab. Invest. 15, 132-147. 

Slater, T.F. (1967). Stimulatory effects of carbon tetrachloride in vim on lipid peroxidation in rat liver microsomes. Proc. 4th FEBS Meeting, Oslo, abstract no. 216, 67. 

Slater, T.F. (1968). The inhibitory effects in vitro of phenothia-zines and other drugs on lipid-peroxidation systems in rat liver microsomes, and their relationship to the liver necrosis produced by carbon tetrachloride. Biochem. J. 106, 155-160. 

On the other hand, microsomes may also directly oxidize or reduce various substrates. As already mentioned, microsomal oxidation of carbon tetrachloride results in the formation of trichloromethyl free radical and the initiation of lipid peroxidation. The effect of carbon tetrachloride on microsomes has been widely studied in connection with its cytotoxic activity in humans and animals. It has been shown that CCI4 is reduced by cytochrome P-450. For example, by the use of spin-trapping technique, Albani et al. [38] demonstrated the formation of the CCI3 radical in rat liver microsomal fractions and in vivo in rats. McCay et al. [39] found that carbon tetrachloride metabolism to CC13 by rat liver accompanied by the formation of lipid dienyl and lipid peroxydienyl radicals. The incubation of carbon tetrachloride with liver cells resulted in the formation of the C02 free radical (identified as the PBN-CO2 radical spin adduct) in addition to trichoromethyl radical [40]. It was found that glutathione rather than dioxygen is needed for the formation of this additional free radical. The formation of trichloromethyl radical caused the inactivation of hepatic microsomal calcium pump [41]. 

Lipid peroxidation is probably the most studied oxidative process in biological systems. At present, Medline cites about 30,000 publications on lipid peroxidation, but the total number of studies must be much more because Medline does not include publications before 1970. Most of the earlier studies are in vitro studies, in which lipid peroxidation is carried out in lipid suspensions, cellular organelles (mitochondria and microsomes), or cells and initiated by simple chemical free radical-produced systems (the Fenton reaction, ferrous ions + ascorbate, carbon tetrachloride, etc). In these in vitro experiments reaction products (mainly, malon-dialdehyde (MDA), lipid hydroperoxides, and diene conjugates) were analyzed by physicochemical methods (optical spectroscopy and later on, HPLC and EPR spectroscopies). These studies gave the important information concerning the mechanism of lipid peroxidation, the structures of reaction products, etc. 

The second mechanism is realized when organic or inorganic compounds are reduced by endogenous reductants (for example, by NADH or NADPH and the other components of mitochondrial or microsomal respiratory chains). The typical compounds are anthracycline antibiotics and carbon tetrachloride. CC14 is easily reduced by microsomes to the free radical CC13 , which is able to abstract a hydrogen atom from unsaturated lipids and initiate lipid peroxidation. Because of this, the CCl4-initiated lipid peroxidation is a reliable and frequently applied model system for the study of in vitro iron-independent lipid peroxidation and the effects of antioxidants (see for example Ref. [54]). 

Vohra and Hui [352] showed that the pretreatment of cultured neutrons with taurine suppressed lipid peroxidation and the loss of glutathione peroxidase activity induced in these cells by carbon tetrachloride. 

Nachtomi E, Alumot E. 1972. Comparison of ethylene dibromide and carbon tetrachloride toxicity in rats and chicks Blood and liver levels lipid peroxidation. Exp Mol Pathol 16 71-78. 

The relative importance of hepatic microsomal lipid peroxidation versus covalent binding of carbon tetrachloride-derived radicals has been the subject of considerable debate. Since cytochrome P-450 loss has been shown to be related to lipid peroxidation and to covalent binding, each in the absence of the other, both of these early consequences of carbon tetrachloride metabolism may contribute to P-450 destruction. Nevertheless, it is still not clear how these initial events are related to subsequent triglyceride accumulation, polyribosomal disaggregation, depression of protein synthesis, cell membrane breakdown and eventual death of the hepatocytes. Carbon tetrachloride... 

Haloalkanes. Certain haloalkanes and haloalkane-containing mixtures have been demonstrated to potentiate carbon tetrachloride hepatotoxicity. Pretreatment of rats with trichloroethylene (TCE) enhanced carbon tetrachloride-induced hepatotoxicity, and a mixture of nontoxic doses of TCE and carbon tetrachloride elicited moderate to severe liver injury (Pessayre et al. 1982). The researchers believed that the interaction was mediated by TCE itself rather than its metabolites. TCE can also potentiate hepatic damage produced by low (10 ppm) concentrations of carbon tetrachloride in ethanol pretreated rats (Ikatsu and Nakajima 1992). Acetone was a more potent potentiator of carbon tetrachloride hepatotoxicity than was TCE, and acetone pretreatment also enhanced the hepatotoxic response of rats to a TCE-carbon tetrachloride mixture (Charbonneau et al. 1986). The potentiating action of acetone may involve not only increased metabolic activation of TCE and/or carbon tetrachloride, but also possible alteration of the integrity of organelle membranes. Carbon tetrachloride-induced liver necrosis and lipid peroxidation in the rat has been reported to be potentiated by 1,2- dichloroethane in an interaction that does not involve depletion of reduced liver glutathione, and that is prevented by vitamin E (Aragno et al. 1992). 

Relative importance of covalent binding and lipid peroxidation in carbon tetrachloride-induced liver toxicity role of cell calcuim, protein and phospholipid degradation development of treatments/ antidotes. 

Biasi F, Albano E, Chiarpotto E, et al. 1991. In vivo and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride. Cell Biochem Func 9 111-118. 

Camps J, Bargallo T, Gimenez A, et al. 1992. Relationship between hepatic lipid peroxidation and fibrogenesis in carbon tetrachloride-treated rats effect of zine administration. Clinical Science 83 695-700. 

Castro GD, Diaz-Gomez Ml, Castro JA. 1990. Biotransformation of carbon tetrachloride and lipid peroxidation promotion by liver nuclear preparations from different animal species. Cancer Lett 53 9-15. 

De Toranzo EG, Diaz Gomez Ml, Castro JA. 1978a. Carbon tetrachloride activation, lipid peroxidation and liver necrosis in different strains of mice. Res Common Chem Pathol Pharmacol 19 347- 352. 

Diaz Gomez Ml, De Castro CR, D Acosta N, et al. 1975. Species differences in carbon tetrachloride-induced hepatotoxicity the role of CCN activation and of lipid peroxidation. Toxicol AppI Pharmacol 34 102-114. 

Dogterom P, Nagelkerke JF, van Steveninick J, et al. 1988. Inhibition of lipid peroxidation by disulfiram and diethydithiocarbamate does not prevent hepatotoxin-induced cell death in isolated rat hepatocytes. A study with allyl alcohol, tert-butyl hydroperoxide, diethyl maleate, bromoisovalerylurea and carbon tetrachloride. Chem Biol Interact 66 251-265. 

Glende EA Jr., Hruszkewycz AM, Recknagel RO. 1976. Critical role of lipid peroxidation in carbon tetrachloride-induced loss of aminopyrine demethylase, cytochrome P-450 and glucose 6-phosphatase. Biochem Pharmacol 25 21663-2170. 

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. J Nutr 107 656-665. 

Kefalas v, Stacey NFI. 1989. Potentation of carbon tetrachloride-induced lipid peroxidation by trichloroethylene in isolated rat hepatocytes no role in enhanced toxicity. Toxicol AppI Pharmacol 101 158-169. 

Kostyuk VA, Potapovich Al. 1991. Damage of rat liver microsomal mixed function oxidase system by carbon tetrachloride in wVo study with selective inhibitor of lipid peroxidation. Biochemistry International 25 349- 353. 

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