The role of glutathione in chloroform-induced hepatotoxicity

Docks, Edward L.; Krishna, Gopal

doi:10.1016/0014-4800(76)90053-8

Cited by 107 publications

(26 citation statements)

References 8 publications

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“…The hepatotoxicity of chloroform appears to be related to its metabolism, presumably due to the covalent binding of its metabolite phosgene to cellular macromolecules, leading to cell death (34,35). Pretreatment of rats with phenobarbital enhanced the metabolism and the hepatotoxicity of chloroform, while cysteine treatment was protective against chloroform-induced hepatocellular necrosis.…”

Section: Trihalomethanesmentioning

confidence: 99%

Implications for risk assessment of suggested nongenotoxic mechanisms of chemical carcinogenesis.

Melnick

Kohn

Portier

1996

Environ Health Perspect

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Section: Trihalomethanesmentioning

confidence: 99%

Implications for risk assessment of suggested nongenotoxic mechanisms of chemical carcinogenesis.

Melnick

Kohn

Portier

1996

Environ Health Perspect

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“…In comparison with CHC13, CC14 produces relatively small amounts of COC12. In vivo, CHC13 administration reduces hepatic GSH considerably but CC14 administration reduces hepatic GSH only slightly, if at all (25,26). Accordingly, diglutathionyl dithiocarbonate, the product of the reaction of COC12 and GSH, is found in the bile of CHCl3-treated rats at 25 times the level of that found in CCl4-treated rats and its formation by microsomes in vitro with these two substrates is in the same proportion (26).…”

Section: Aerobic Metabolismmentioning

confidence: 99%

Biochemical studies on the metabolic activation of halogenated alkanes.

Cheeseman¹,

Albano²,

Tomasi³

et al. 1985

Environ Health Perspect

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This paper reviews recent investigations by Slater and colleagues into the metabolic activation of halogenated alkanes in general and carbon tetrachloride in particular. It is becoming increasingly accepted that free radical intermediates are involved in the toxicity of many such compounds through mechanisms including lipid peroxidation, covalent binding, and cofactor depletion. Here we describe the experimental approaches that are used to establish that halogenated alkanes are metabolized in animal tissues to reactive free radicals. Electron spin resonance spectroscopy is used to identify free-radical products, often using spin-trapping compounds. The generation of specific free radicals by radiolytic methods is useful in the determination of the precise reactivity of radical intermediates postulated to be injurious to the cell. The enzymic mechanism of the production of such free radicals and their subsequent reactions with biological molecules is studied with specific metabolic inhibitors and free-radical scavengers. These combined techniques provide considerable insight into the process of metabolic activation of halogenated compounds. It is readily apparent, for instance, that the local oxygen concentration at the site of activation is of crucial importance to the subsequent reactions; the formation of peroxy radical derivatives from the primary free-radical product is shown to be of great significance in relation to carbon tetrachloride and may be of general importance. However, while these studies have provided much information on the biochemical mechanisms of halogenated alkane toxicity, it is clear that many problems remain to be solved.

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“…Ilett et al (1973) have shown that the microsomal MFO inducer, phenobarbital, increases toxicity, whereas piperonyl butoxide--an inhibitor of MFOs--inhibits toxicity in mice treated with chloroform. (Bhooshan et al, 1977;Pohl, 1979) and that intracellular glutathione is the primary nucleophile responsible for detoxification (Brown et al, 1974a;Docks and Krishna, 1976). Reitz et al (1980) and Moore et al (1980) have postulated that the carcinogenic effect observed in animals after oral administration of chloroform has an epigenetic mechanism.…”

Section: Pharmacokinetics and Molecular Interactionmentioning

confidence: 99%

Emergency and Continuous Exposure Limits for Selected Airborne Contaminants. Volume 1

Lazen¹

1984

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The role of glutathione in chloroform-induced hepatotoxicity

Cited by 107 publications

References 8 publications

Implications for risk assessment of suggested nongenotoxic mechanisms of chemical carcinogenesis.

Implications for risk assessment of suggested nongenotoxic mechanisms of chemical carcinogenesis.

Biochemical studies on the metabolic activation of halogenated alkanes.

Emergency and Continuous Exposure Limits for Selected Airborne Contaminants. Volume 1

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