Carbon tetrachloride-induced protection against carbon tetrachloride toxicity

Glende, Eric A.

doi:10.1016/0006-2952(72)90076-7

Cited by 127 publications

(24 citation statements)

References 14 publications

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“…Thus, the destruction of liver microsomal cytochrome P450 (3,20, 3 1 , 33) by the protective dose of CCI, presumably causes a decrease in bioactivation of subsequently administered high dose of CCI,, which results in decreased toxicity (8,29,32). Consistent with this widely accepted concept for CCI, autoprotection, the protective dose has been shown to decrease hepatic 47 TOXICOLOGIC PATHOLOGY cytochrome P450 and associated aminopyrine demethylase activity (10,20) resulting in decreased conversion of subsequently administered high dose of ccl, to co, (35).…”

Section: Introductionsupporting

confidence: 51%

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Role of Hepatocellular Regeneration in CCl₄ Autoprotection

Thakore

Mehendale

1991

Toxicol Pathol

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ABsTFZACXThe destruction of liver microsomal cytochromes P4so by a previously administered low dose of CCl, has been widely accepted as the mechanism of CCl, autoprotection. However, circumstantial evidence suggests that this mechanism cannot completely explain the phenomenon of autoprotection. The protective effect of a low dose of CCl, (0.3 mVkg, PO) on the lethal effect of a subsequently administered high dose (5 mUkg, PO) was established in male Sprague Dawley rats. The protective dose permitted 100% survival, whereas only 15% survival was observed without it. Hepatotoxicity, measured by serum enzyme elevations (aspartate transaminase, alanine transaminase, and sorbitol dehydrogenase) and histopathological changes 24 hr after the treatment with high dose, was similar in both the groups, even though the protective dose had significantly decreased liver microsomal cytochromes P,,, (to 62% of normal) and associated enzymes, aminopyrine demethylase and aniline hydroxylase. Rats pretreated with CoCl, to decrease hepatic microsomal cytochrome P450 to 44% of normal levels did not show a significant protection from the hepatotoxicity of high dose of CCI,. Previous studies have established that hepatocellular regeneration is stimulated within 6 hr after the administration of a low dose of CCI,. Based on this observation, a premise that autoprotection results from augmented recovery from injury rather than decreased injury appears likely. Hence, the role of hepatocellular regeneration was evaluated by following 'H-thymidine incorporation in hepatocellular nuclear DNA, labelling index by autoradiography, and by morphometric estimation of mitotic index. After administration of the protective dose of CCl,, stimulated nuclear DNA synthesis measured by 3H-thymidine incorporation into nuclear DNA was increased and this remained high even after subsequent administration of high dose of CCl,. Forty-eight hr after the administration of a lethal dose of CCl, alone (5 mVkg, po), labelling index was slightly increased, but mitotic index was not increased. In the surviving rats (15%), both labelling index and mitotic index were significantly elevated after an additional 24 hr. In rats receiving the protective dose, a significantly greater elevation of labelling index as well as mitotic index occurred 48 hr after the administration of the same lethal dose of CCl,. These results suggest that hepatocellular regeneration stimulated by the protective dose, as a biological response recruited to overcome the accompanying limited injury, may augment and sustain tissue repair processes to permit tissue restoration even after the massive liver injury elicited by the subsequent large dose of CCI,.

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Section: Introductionsupporting

confidence: 51%

“…The protective effect of a small dose of CCl,, against a second, normally lethal dose of CCl, administered 24 hr later, is well known (8,10,35,36). The currently accepted mechanism for CCl, autoprotection is based on the destruction of the CCl, bioactivating mechanism by the protective dose.…”

Section: Introductionmentioning

confidence: 99%

Role of Hepatocellular Regeneration in CCl₄ Autoprotection

Thakore

Mehendale

1991

Toxicol Pathol

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“…In this instance, pretreatment of animals with a small dose of a chemical results in protection against a subsequently administered lethal dose of the same compound, and consequently the animals do not die even from a lethal dose [1][2][3][4] . Stimulated cell division by treatment with a sublethal dose of CCl 4 or thioacetamide exhibited less sensitivity to a lethal dose of the same compound due to the mechanism of autoprotection 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Acquired Resistance to Bromobenzene Hepatotoxicity by Repeated Treatment of Rats with Bromobenzene

et al. 2005

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It has often been observed that chemical-induced initial insult is no longer detected in examinations after additional consecutive treatments, suggesting that the target organs acquire resistance to chemical toxicity. In this study, we examined whether acquired resistance to toxicity would be observed after repeated treatments of a toxic dose of bromobenzene (BB). In Experiment 1, F344 male rats were intraperitoneally given BB at a dosage of 150 mg/kg/day. Based on the serum AST level 20 h after the first treatment, the rats were divided into 2 groups, Groups 2 and 3, which consisted of rats with elevated AST and rats without remarkable changes in AST activity, respectively. Subsequently, the rats were subjected to the same BB treatment regimen for 4 or 9 consecutive days. The control group (Group 1) was administered with the vehicle. The AST activity of Group 2 showed no remarkable changes from Day 3, indicating an acquired resistance to BB hepatotoxicity. Measurements of drug-metabolizing enzymes in Group 2 demonstrated a reduction in CYP contents and activities, and a strong induction of GST, which contributed to the resistance. The aminotransferase activities in Group 3, however, showed no changes throughout the dosing periods. In Experiment 2, the rats with the same BB treatment regimen as Experiment 1 were administered intraperitoneally with a single dosage of BB of 300 mg/kg. Although a higher dosing of BB caused hepatic injury in all three groups, the degree of injury in the two groups with BB treatment was much slighter than that in the control (vehicle + BB). These results indicate that not only Group 2 but also Group 3 acquired resistance to BB hepatotoxicity after repeated treatments. The exposure levels of BB in the two groups were lower than those of the control. Thus, changes in the drug-metabolizing reaction related to the metabolism and detoxification of BB contributed to the resistance to BB hepatotoxicity. (J Toxicol Pathol 2005; 18: 189-198)

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“…This may be analogous to the protection afforded by a small dose of CC14 against injury from a large dose of CC14 subsequently administered (10). In contrast, livers of animals exposed to VCM on five consecutive days and who were not pretreated with PBT appeared normal.…”

Section: Resultsmentioning

confidence: 76%

Acute Liver Injury by Vinyl Chloride: Involvement of Endoplasmic Reticulum in Phenobarbital-Pretreated Rats

Reynolds¹,

Jaeger²,

Murphy³

1975

Environmental Health Perspectives

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A single 6-hr exposure to vinyl chloride monomer (5%o) produces extensive vacuolization of centrolobular liver parenchyma and focal midzonal necrosis in the hepatic lobuole in phenobarbital-pretreated rats. Ultrastructurally, vacuolization consists of dilation of cysternae of rough endoplasmic reticulum and in the same cells smooth endoplasmic reticulum coalesces into discreet aggregates resembling denatured membranes. The findings support the hypothesis that vinyl chloride is hepatotoxic because it is converted into a toxic metabolite by components of the mixed function oxidase system of liver endoplasmic reticulum.

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Carbon tetrachloride-induced protection against carbon tetrachloride toxicity

Cited by 127 publications

References 14 publications

Role of Hepatocellular Regeneration in CCl₄ Autoprotection

Role of Hepatocellular Regeneration in CCl₄ Autoprotection

Acquired Resistance to Bromobenzene Hepatotoxicity by Repeated Treatment of Rats with Bromobenzene

Acute Liver Injury by Vinyl Chloride: Involvement of Endoplasmic Reticulum in Phenobarbital-Pretreated Rats

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Carbon tetrachloride-induced protection against carbon tetrachloride toxicity

Cited by 127 publications

References 14 publications

Role of Hepatocellular Regeneration in CCl4 Autoprotection

Role of Hepatocellular Regeneration in CCl4 Autoprotection

Acquired Resistance to Bromobenzene Hepatotoxicity by Repeated Treatment of Rats with Bromobenzene

Acute Liver Injury by Vinyl Chloride: Involvement of Endoplasmic Reticulum in Phenobarbital-Pretreated Rats

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Role of Hepatocellular Regeneration in CCl₄ Autoprotection

Role of Hepatocellular Regeneration in CCl₄ Autoprotection