Specificity of a phenobarbital-induced cytochrome P-450 for metabolism of carbon tetrachloride to the trichloromethyl radical

Noguchi, Takehiko; Fong, Kuo-Lan; Lai, Edward K.; Alexander, S; King, M. Margaret; Olson, Larry; Poyer, J. Lee; McCay, Paul B.

doi:10.1016/0006-2952(82)90440-3

Cited by 173 publications

(51 citation statements)

References 25 publications

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“…In general, a number of chemicals including various environmental toxicants and even clinically useful drugs can cause severe cellular damages in different organs of the body through metabolic activation to highly reactive substances such as free radicals (Noguchi et al, 1982). CCl 4 is one of such widely used environmental toxicant to experimentally induce animal models of acute nephrotoxicity and .…”

Section: Discussionmentioning

confidence: 99%

Effect of melatonin on carbon tetrachloride- induced kidney injury in wistar rats

Adewole¹,

Salako²,

Doherty³

et al. 2010

African Journal of Biomedical Research

100

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Exposure to carbon tetrachloride (CCl 4 ) induces acute and chronic renal injuries as well as oxidative stress in rats. The aim of this study was to evaluate the effect of exogenous melatonin (MEL) treatment on CCl 4 -induced oxidative stress and nephrotoxicity in rats using histopathological and biochemical parameters. Serum creatinine, blood urea nitrogen (BUN), nitrite and albumin concentrations were measured for the evaluation of renal function. Antioxidant status in the kidney tissue was estimated by determining the activities of superoxide dismustase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and glutathione-S-transferase (GST) as well as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH

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Section: Discussionmentioning

confidence: 99%

Effect of melatonin on carbon tetrachloride- induced kidney injury in wistar rats

Adewole¹,

Salako²,

Doherty³

et al. 2010

African Journal of Biomedical Research

100

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“…The first metabolite, a trichloromethyl free radical (.CCl 3 ) [21] has been formed from the metabolic conversion of CCl 4 and reacts very rapidly with O 2 and forms a second metabolite, a trichloromethyl peroxy free radical (CCl 3 OO) [22] or abstract hydrogen atoms to form chloroform. These free radicals initiate the peroxidation of membrane poly-unsaturated fatty acids and covalently bind to microsomal lipids and proteins [23].…”

Section: Discussionmentioning

confidence: 99%

Protective efficacy of natansnin, a dibenzoyl glycoside from Salvinia natans against CCl4 induced oxidative stress and cellular degeneration in rat liver

et al. 2010

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BackgroundCarbon tetra chloride (CCl4), an industrial solvent, is a hepatotoxic agent and it is the well established animal model for free radical-induced liver injury. The present investigation was carried out to establish the protective effect of natansnin, a novel dibenzoyl glycoside from Salvinia natans against CCl4 induced oxidative stress and cellular degeneration in rat liver.ResultsCCl4 significantly increased the levels of lipid peroxides, oxidized glutathione and decreased the levels of reduced glutathione, SOD and CAT. CCl4 induce marked histopathological changes and increase in the levels of apoptotic proteins. CCl4 treatment significantly increased the levels of apoptotic proteins such as caspases-3, PARP, Bax, Bid and cytochrome C and also increased the levels of inflammatory mediators iNos and Cox-2. Natansnin treatment significantly decreased the levels of CCl4 induced apoptotic proteins and inflammatory mediators. Further natansinin treatment significantly inhibited the CCl4 induced apoptosis which was evident form the reduced TUNEL positive cells.ConclusionsIn conclusion, our study demonstrated the protective effect of natansnin against CCl4 induced oxidative stress and cellular degeneration in rat liver tissue. This protective effect of natansnin can be correlated to its direct antioxidant effect.

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“…It was reported that CC14-evoked liver injury was enhanced in phenobarbitalinduced animals (23). Noguchi et al (24) further showed that the phenobarbital-inducible form of P-450 was capable of generating the trichloromethyl free radical in the reconstituted enzyme system. The present study also showed similar results in that phenobarbital considerably increased the amount of P-450 and the activities of drugmetabolizing enzymes, and it markedly increased liver degeneration and necrosis induced by a large dose of CC14.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Rifampicin against Acute Liver Injury Induced by Carbon Tetrachloride in Mice

Huang

Okuno

Takasu

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-Rifampicin conferred significant protection against carbon tetrachloride (CC14)-induced liver injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were not markedly altered and only hepatocellular fatty degeneration was found in mice pretreated with rifampicin (200 mg/kg), whereas severe centrilobular necrosis was observed and serum ALT and AST activities were as high as 281 and 271 I.U./1, respectively, in the control group following administration of CC14 (400,ul/kg). The contents and activities of microsomal drug-metabolizing enzymes in rifampicin-pretreated animals were also much higher than those of the controls. CC14-mediated malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CC14 catalyzed by P-450 2E1 to produce free radicals. However, MDA formation was obviously depressed by rifampicin at varying concentrations from 2 to 32 x 10-6 M in an in vitro cytochrome P-450 (P-450) enzyme system. On the other hand, NADPH oxidation in the metabolism of CC14 and aniline hydroxylation were not suppressed in the presence of rifampicin in this systems, suggesting that rifampicin did not influence the biotransformation of CC14 by P-450 2E1 in vitro. Therefore, the protective effect of rifampicin against CC14 hepatotoxicity appeared to result from the direct inhibition of lipid peroxidation generated by CC14-derived free radicals.

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Specificity of a phenobarbital-induced cytochrome P-450 for metabolism of carbon tetrachloride to the trichloromethyl radical

Cited by 173 publications

References 25 publications

Effect of melatonin on carbon tetrachloride- induced kidney injury in wistar rats

Effect of melatonin on carbon tetrachloride- induced kidney injury in wistar rats

Protective efficacy of natansnin, a dibenzoyl glycoside from Salvinia natans against CCl4 induced oxidative stress and cellular degeneration in rat liver

Protective Effect of Rifampicin against Acute Liver Injury Induced by Carbon Tetrachloride in Mice

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