Carbon tetrachloride, hepatotoxicity

Williams, A.T. and Burk, R.F. (1990). Carbon tetrachloride hepatotoxicity, an example of free radical-mediated injury. Semin. Liver Dis. 10, 279-284. 

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. 

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

Agarwal AK, Mehendale HM. 1983b. Effect of adrenalectomy on chlordecone potentiation of carbon tetrachloride hepatotoxicity. Fundam Appl Toxicol 3(6) 507-511. 

Agarwal AK, Mehendale HM. 1983c. Potentiation of carbon tetrachloride hepatotoxicity and lethality by chlordecone in female rats. Toxicology 26(3-4) 231-242. 

Bell AN, Mehendale HM. 1985. ne effect of dietary exposure to a mirex plus chlordecone combination on carbon tetrachloride hepatotoxicity. Fundam Appl Toxicol 5(4) 679-687. 

Bell AN, Young RA, Lockard VG, et al. 1988. Protection of chlordecone-potentiated carbon tetrachloride hepatotoxicity and lethality by partial hepatectomy. Arch Toxicol 61 392-405. 

Britton RS, Dolak JA, Glende EA Jr, et al. 1987. Potentiation of carbon tetrachloride hepatotoxicity by chlordecone Dose-response relationships and increased covalent binding in vivo. J Biochem Toxicol 2 43-55. 

Cai Z, Mehendale HM. 1993. Resiliency to amplification of carbon tetrachloride hepatotoxicity by chlordecone during postnatal development in rats. Pediatric Research 33(3) 225-232. 

Curtis LR, Mehendale HM. 1980. Specificity of chlordecone-induced potentiation of carbon tetrachloride hepatotoxicity. Drug Metab Dispos 8 23-27. 

Ebel RE, McGrath EA. 1984. Carbon tetrachloride-hepatotoxicity in the Mongolian gerbil Influence of monooxygenase system induction. Toxicol Lett 22(2) 205-210. 

Kodavanti PR, Joshi UM, Mehendale HM, et al. 1989a. Chlordecone (Kepone )- potentiated carbon tetrachloride hepatotoxicity in partially hepatectomized rats A histomorphometric study. J Appl Toxicol 9(6) 367-375. 

Kodavanti PR S, Kodavanti UP, Mehendale HM. 1990b. Altered hepatic energy status in chlordecone (Kepone)-potentiated carbon tetrachloride hepatotoxicity. Biochem Pharmacol 40(4) 859-866. 

Kodavanti PRA, Rao VC, Mehendale HM. 1993. Loss of calcium homeostasis leads to progressive phase of chlordecone-potentiated carbon tetrachloride hepatotoxicity. Toxicol Appl Pharinaeol 122 77- 87. 

Tockard VG, Mehendale HM, O Neal RM. 1983a. Chlordecone-induced potentiation of carbon tetrachloride hepatotoxicity A light and electron microscopic study. Exp Mol Pathol 39 230-245... 

Rao SB, Mehendale HM. 1989. Protection from chlordecone (Kepone)-potentiated carbon tetrachloride hepatotoxicity in rats by fructose 1,6-diphosphate. Int J Biochem 21(9) 949-954. 

The mechanism of carbon tetrachloride hepatotoxicity generally is viewed as an example of lethal cleavage, where the CCh— Cl bond is split in the mixed-function oxidase system of the hepatocytes. After this cleavage damage may occur directly from the free radicals (-CCl and -Cl) and/or from the formation of toxic metabolites such as phosgene." ... 

Pilon D, Charbonneau M, Brodeur J, et al. 1986. Metabolites and ketone body production following methyl n-butyl ketone exposure as possible indices of MnBK potentiation of carbon tetrachloride hepatotoxicity. Toxicol AppI Pharmacol 85 49-59. 

Therefore, in spite of remarkably increased liver injury, the animals are able to overcome injury and survive the potentiated liver toxicity (Kodavanti et al. 1992 Mehendale 1990, 1991, 1992). DDT increased the sensitivity of rats to carbon tetrachloride poisoning (McLean and McLean 1966), and mice fed 100 ppm polybrominated biphenyls (PBBs) or 200 ppm polychlorinated biphenyls (RGBs) in their diet for 28 days experienced increased carbon tetrachloride hepatotoxicity (Kluwe et al. 1979). Potentiation of renal dysfunction was also found in the PBB-pretreated mice. All of these compounds are broad-spectrum MFO inducers. 

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). 

Nutritional status can also influence the toxic potency of carbon tetrachloride. Animal studies have clearly demonstrated that brief fasting or consumption of diets low in antioxidants (vitamin E, selenium, methionine) can lead to increased carbon tetrachloride hepatotoxicity. The same may be true for humans, although this is not known for certain. Another aspect of nutritional status affecting carbon tetrachloride toxicity is hepatic energy status. Hepatic ATP levels might influence the ultimate outcome of toxicity (low levels may inhibit recovery mechanisms). 

Role of alterations in cellular phospholipid in carbon tetrachloride hepatotoxicity Ca2+-dependent i ncreases i n phospholipid destruction mediated by phospholipase... 

Mechanism of carbon tetrachloride hepatotoxicity kinetics of metabolism and effects on cellular organel1es. 

Brattin WJ, Glende EA Jr., Recknagel RD. 1985. Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radical Biol Med 1 27-38. 

Burk RF, Reiter R, Lane JM. 1986. Hyperbaric oxygen protection against carbon tetrachloride hepatotoxicity in the rat. Association with altered metabolism. Gastroenterol 90 812-818. 

Clawson GA. 1989. Mechanisms of carbon tetrachloride hepatotoxicity. Pathol Immunopathol Res 8 104-112. 

DiSilvestro RA, Medeiros DM. 1992. Low and marginal copper intake by postweaning rats effects on copper status and resistance to carbon tetrachloride hepatotoxicity. Metabolism 41 1122-1124. 

Kenel MF, Kulkarni AP. 1985a. Ethanol potentiation of carbon tetrachloride hepatotoxicity possible role for the in wVo inhibition of aldehyde dehydrogenase. Gen Pharmacol 16 355-360. 

Masuda Y, Nakamura Y. 1990. Effects of oxygen deficiency and calcium omission on carbon tetrachloride hepatotoxicity in isolated perfused livers from phenobarbital-pretreated rats. Biochem Pharmacol 40 1865-1876. 

Recknagel RO, Glende EA Jr. 1973. Carbon tetrachloride hepatotoxicity An example of lethal cleavage. CRC Crit Rev Toxicol 2 263-297. 

Shertzer HG, Niemi MP, Reitman FA, et al. 1987. Protection against carbon tetrachloride hepatotoxicity by pre-treatment with indo1-3-carbinol. Exper Mol Pathol 46 180-189. 

Traiger GJ, Bruckner JV. 1976. The participation of 2-butanone in 2-butanol- induced potentiation of carbon tetrachloride hepatotoxicity. J Pharmacol Exp Therap 196 493-500. 

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