Mechanisms of carbon tetrachloride toxicity

Recknagel, Richard O.; Glende, Eric A.; Dolak, James A.; Waller, Robert L.

doi:10.1016/0163-7258(89)90050-8

Cited by 1,120 publications

(800 citation statements)

References 90 publications

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“…CCl 4 induced liver injuries are the best characterized system of xenobiotic-induced hepatotoxicity and for the screening of anti-hepatotoxic or hepatoprotective activities of drugs [16]. To our knowledge, this is the first study to demonstrate that prior administration of natansnin ameliorated CCl 4 -induced acute liver injury in rats as evidenced by both oxidative, cellular degeneration and cell death parameters mentioned above.…”

Section: Discussionmentioning

confidence: 89%

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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Section: Discussionmentioning

confidence: 89%

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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“…52 Following production of toxic reactive intermediates, autocatalytic lipid peroxidation is suggested to damage cellular macromolecules, but the cellular mechanisms responsible for CCl 4 -induced hepatic cell death are poorly understood. 53 The HepG2 cells used here do not express significant amounts of the enzyme. 54 Since PTD-FNK retained the intracellular level of ATP and mitochondrial membrane potential, the protein seems to preserve functional mitochondria to protect cells.…”

Section: Discussionmentioning

confidence: 99%

“…[53][54][55][56] CCl 4 affects intracellular Ca 2 þ content and seems to inhibit differently calcium transport systems on the cytoplasmic, mitochondrial and ER membranes. 56 Calcium ions activate lytic enzymes such as phospholipase A2 that may cause disintegrity of the organelle membrane, including the cytoplasmic membrane.…”

Section: Discussionmentioning

confidence: 99%

Zonal necrosis prevented by transduction of the artificial anti-death FNK protein

et al. 2005

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Protection of cells from necrosis would be important for many medical applications. Here, we show protein transduction domain (PTD)-FNK therapeutics based on protein transduction to prevent necrosis and acute hepatic injury with zonal death induced by carbon tetrachloride (CCl 4 ). PTD-FNK is a fusion protein comprising the HIV/Tat PTD and FNK, a gain-offunction mutant of anti-apoptotic Bcl-x L . PTD-FNK protected hepatoma HepG2 from necrotic death induced by CCl 4 , and additionally, increased the apoptotic population among cells treated with CCl 4 . A concomitant treatment with a pancaspase inhibitor Z-VAD-FMK (N-benzyloxycarbonyl-Val-AlaAsp-fluoromethylketone), which alone could not prevent the necrosis, protected these cells from the apoptosis. When preinjected intraperitoneally, PTD-FNK markedly reduced zonal liver necrosis caused by CCl 4 . Moreover, injection of PTD-FNK accompanied by Z-VAD-FMK suppressed necrotic injury even after CCl 4 administration. These results suggest that PTD-FNK has great potential for clinical applications to prevent cell death, whether from apoptosis or necrosis, and organ failure.

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“…CCl 4 is widely used as a toxin to induce liver injury in rats. The toxicity induced by CCl 4 is recognized by free radicals, mainly trichloromethyl radical ( CCl 3 ) and its peroxyl radical ( OOCCl 3 ), which initiate the chain reaction of lipid peroxidation and cause subsequent cell damage [30,31]. Recently, Huang et al [32] performed GC/MS-based metabolic profiling of plasma in CCl 4 -induced mice and Lin et al [33] introduced LC/MS for metabonomic analysis of urine from CCl 4 -induced rats.…”

Section: Applicationmentioning

confidence: 99%

An optimized procedure for metabonomic analysis of rat liver tissue using gas chromatography/time-of-flight mass spectrometry

Qiu

Chen

et al. 2010

Journal of Pharmaceutical and Biomedical Analysis

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Abstract:In this paper, we present a tissue metabonomic method with an optimized extraction procedure followed by instrumental analysis with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) and spectral data analysis with multivariate statistics. Metabolite extractions were carried out using three solvents: chloroform, methanol, and water, with design of experiment (DOE) theory and multivariate statistical analysis. A two-step metabolite extraction procedure was optimized using a mixed solvent of chloroform-methanol-water (1:2:1, v/v/v) and then followed by methanol alone. This approach was subsequently validated using standard compounds and liver tissues. Calibration curves were obtained in the range of 0.50-125.0 μg/mL for standards and 0.02-0.25 g/mL acceptable for liver tissue samples. For most of the metabolites investigated, relative standard deviations (RSD) were below 10% within a day (reproducibility) and below 15% within a week (stability). Rat liver tissues of carbon tetrachloride-induced acute liver injury models (n = 10) and healthy control rats (n = 10) were analyzed which demonstrated the applicability of the developed procedure for the tissue metabonomic study.

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Mechanisms of carbon tetrachloride toxicity

Cited by 1,120 publications

References 90 publications

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

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

Zonal necrosis prevented by transduction of the artificial anti-death FNK protein

An optimized procedure for metabonomic analysis of rat liver tissue using gas chromatography/time-of-flight mass spectrometry

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