Carbon Tetrachloride Hepatotoxicity: An Example of Lethal Cleavage

Rechnagel, Richard O.; Glende, Eric A.; Plaa, Gàbriel L.

doi:10.3109/10408447309082019

Cited by 671 publications

(200 citation statements)

References 162 publications

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“…The primary step in CC14 metabolism is reductive and consists of transfer of an electron to CC14 by the P-450 system yielding CC13* (18). There is also evidence for a two-electron reduction yielding dichlorocarbene, but this step seems to be quantitatively minor (19).…”

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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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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“…For example, experimental acute liver injury with CCl 4 is characterized by centrilobular necrosis resulting from the formation of free radicals and reactive oxygen species during the metabolism of CCl 4 by cytochrome P450 and the activation of Kupffer cells by free radicals (Recknagel and Glende 1973;Edwards et al, 1993). The damage of liver cells accompanies the release of liver function enzymes, such as g-glutamyl transferase (GGT; EC 2.3.2.2), alanine aminotransferase (ALT; EC 2.6.1.1), and aspartate aminotransferase (AST; EC 2.6.1.2) into the blood (Skinner et al, 1984;Shaper et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Intake of purple sweet potato beverage affects on serum hepatic biomarker levels of healthy adult men with borderline hepatitis

Suda

Ishikawa

Hatakeyama³

et al. 2007

Eur J Clin Nutr

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Objective: To examine the effect of purple sweet potato (PSP) beverage rich in acylated anthocyanins on serum hepatic biomarkers in healthy Japanese men. Design: A randomized, double-blind, placebo-controlled, parallel study. Setting: Kumamoto in Japan. Subjects: Healthy adult men (30-60 years) with borderline hepatitis who had one or more of serum g-glutamyl transferase (GGT), aspertate aminotransferase (AST) and alanine aminotransferase (ALT) levels over normal ranges, and who were negative for hepatitis virus were openly recruited by an advertisement. Of the 48 persons enrolled, 38 (mean age 43.0 years (30-54 years)) completed the study. Methods: The subjects were randomly assigned to the PSP group and the placebo group. During the 8-week intervention, the subjects in the PSP group consumed two bottles of the PSP beverage with acylated anthocyanins (200.3 mg anthocyanins per 125 ml per bottle) per day, and the subjects in the placebo group, two bottles of a placebo beverage (1.7 mg anthocyanins per 125 ml per bottle). All of the data measured were analyzed by two-way repeated measures analysis of variance (ANOVA) with groups and times. The data of the hepatic markers were analyzed using the Dunnett multiple comparison among the time points and t-test between groups at the same time point. Two-sided Po0.05 were defined as the level of significance. Results: Serum GGT, AST and ALT levels showed interactions (Po0.05) between the beverage groups and time; the others were not affected. The PSP beverage group showed lower hepatic marker levels than the placebo group during the ingestion period, particularly the GGT level (À14.1 IU/l, 95% Confidence intervel (CI) À25.4 to À2.7, P ¼ 0.017 at 2 weeks; À16.8 IU/l, 95% CI À36.2 to 2.5, P ¼ 0.081 at 4 weeks; À26.7 IU/l, 95% CI À47.6 to À5.7, P ¼ 0.014 at 6 weeks and À27.9 IU/l, 95% CI À49.9 to À5.9; P ¼ 0.014 at 8 weeks). No correlation between alcohol consumption and each hepatic biomarker level before and after the ingestion was observed. Conclusion: The intake of the PSP beverage significantly decreased the serum levels of hepatic biomarkers, particularly the GGT level, in healthy men with borderline hepatitis.

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“…CC14 and related halogenomethanes are well-known to induce lipid peroxidation (1,4). Furthermore, a large amount of aldehydic compounds are reported to be produced dur ing lipid peroxidation in various biological sys tems including a halogenomethane-induced peroxidation system (7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

“…Lipid peroxidation of biological membranes has been considered to be an important patho logical process in various degenerative tissue injuries, including the earliest example of carbon tetrachloride hepatotoxicity (1)(2)(3)(4). Although a number of biochemical methods have been developed for detecting lipid perox idation (5), histological methods must be de veloped to determine the localization of lipid peroxidation within tissues or organs.…”

mentioning

confidence: 99%

Histological Detection of Lipid Peroxidation Following Infusion of Tert-Butyl Hydroperoxide and ADP-Iron Complex in Perfused Rat Livers.

Masuda¹,

Yamamori²

1991

Jpn.J.Pharmacol

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ABSTRACT-Lipid peroxidation was assessed histologically and biochemically in hemoglobin-free perfused rat livers using two different types of stimulators. The Schiff reaction of fuchsin with cellular aldehydes was used as a histological index for lipid peroxidation. t-Butyl hydroperoxide (BHP, 0.8 mM) infusion caused a rapid and sus tained release of thiobarbituric acid reactive substances (TBARS) into the effluent perfusate for up to 60 min, which was accompanied by lactate dehydrogenase (LDH) leakage after 30 min. The Schiff positive foci were initially restricted to periportal zones and spread with time to whole areas, accompanied by periportal necrosis. Co infusion of diphenyl-p-phenylenediamine suppressed the TBARS release, with nega tive fuchsin staining, but the LDH leakage was unaffected. Under retrograde perfu sion, BHP produced pericentral staining and necrosis. With 2.5 mM ADP-100'U M Fe3+, little TBARS was released up to 60 min, even though the hepatic TBARS levels increased considerably by this time. By 90 min, marked TBARS release occurred, but LDH leakage remained low. Irrespective of the direction of perfusion, pericentral hepatocytes became Schiff positive after 30 min. The fuchsin staining method may be useful for detecting peroxidized zones of the liver lobules.

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Carbon Tetrachloride Hepatotoxicity: An Example of Lethal Cleavage

Cited by 671 publications

References 162 publications

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

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

Intake of purple sweet potato beverage affects on serum hepatic biomarker levels of healthy adult men with borderline hepatitis

Histological Detection of Lipid Peroxidation Following Infusion of Tert-Butyl Hydroperoxide and ADP-Iron Complex in Perfused Rat Livers.

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