Uptake, Distribution, and Elimination of Carbon Tetrachloride in Rat Tissues Following Inhalation and Ingestion Exposures

Sanzgiri, U. Y.; Srivatsan, V.; Muralidhara, Srinivasa; Dallas, Cham E.; Bruckner, James V.

doi:10.1006/taap.1996.8079

Cited by 68 publications

(48 citation statements)

References 23 publications

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“…27) Furthermore, Sanzgiri et al reported that CCl 4 administered systemically in rats was distributed in the kidney at higher concentrations than in the liver. 28) On the basis of these findings, renal damage caused by systemic administration of CCl 4 is reasonable. Renal damage was supported by the renal elevation of lipid peroxidation levels (Fig.…”

Section: )mentioning

confidence: 84%

A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats.

Mukai

Mera

Nishida

et al. 2002

Biological & Pharmaceutical Bulletin

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Animal models prepared by treatment with toxic compounds such as a carbon tetrachloride have been used to examine drug disposition in hepatic diseases. However, it is possible that these compounds accumulate and cause damage to other organs as they are administered systemically. In this study, we used the liver surface application technique to deliver a toxic compound to the liver to prepare an appropriate animal model in which only the liver is significantly damaged. To restrict the absorption area in the liver, a cylindrical diffusion cell was attached to the liver surface of male Wistar rats. Twenty-four hours after direct addition of carbon tetrachloride to the diffusion cell, plasma levels of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), and hepatic malondialdehyde (MDA) concentration were increased, while there were no changes in plasma creatinine or renal MDA level. On the other hand, not only GOT, GPT and hepatic MDA, but also creatinine and renal MDA levels were markedly increased by p.o. and i.p. administration of carbon tetrachloride, suggesting renal damage. These results indicated that the animal models of liver damage prepared by utilizing drug delivery techniques to accumulate toxic compounds in the liver would enable us to investigate the precise effects of hepatic disorder on drug disposition.

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Section: )mentioning

confidence: 84%

A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats.

Mukai

Mera

Nishida

et al. 2002

Biological & Pharmaceutical Bulletin

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“…CYP2E1 has a half-life of 4 to 6 h or less in rat liver (Roberts et al, 1994). Ingested CCl 4 reaches the liver, undergoes metabolic activation, and damages the liver in a matter of minutes (Rao and Recknagel, 1968;Sanzgiri et al, 1997). Thus, there appears to be time during a 24-h period for the necessary sequence of events to occur and to be reversed for subsequent diurnal cycles.…”

Section: Mechanisms Of Circadian Rhythmicity Of CCL 4 Hepatotoxicity 277mentioning

confidence: 99%

Mechanisms of Circadian Rhythmicity of Carbon Tetrachloride Hepatotoxicity

Bruckner

Ramanathan²,

Lee³

et al. 2002

J Pharmacol Exp Ther

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The toxicity of carbon tetrachloride (CCl 4 ) and certain other chemicals varies over a 24-h period. Because the metabolism of some drugs follows a diurnal rhythm, it was decided to investigate whether the hepatic metabolic activation of CCl 4 was rhythmic and coincided in time with maximum susceptibility to CCl 4 hepatotoxicity. A related objective was to test the hypothesis that abstinence from food during the sleep cycle results in lipolysis and formation of acetone, which participates in induction of liver microsomal cytochrome P450IIE1 (CYP2E1), resulting in a diurnal increase in CCl 4 metabolic activation and acute liver injury. Groups of fed and fasted male Sprague-Dawley rats were given a single oral dose of 800 mg of CCl 4 /kg at 2-to 4-h intervals over a 24-h period. Serum enzyme activities, measured 24 h post dosing as indices of acute liver injury, exhibited distinct maxima in both fed and fasted animals dosed with CCl 4 near the beginning of their dark/active cycle. Blood acetone, hepatic CYP2E1 activity, and covalent binding of 14 CCl 4 /metabolites to hepatic microsomal proteins in untreated rats fed ad libitum followed circadian rhythms similar to that of susceptibility to CCl 4 . Parallel fluctuations of greater amplitude were seen in rats fasted for 24 h. Hepatic glutathione levels were lowest at the time of greatest susceptibility to CCl 4 . Acetone dose-response experiments showed high correlations between blood acetone levels, CYP2E1 induction, and CCl 4 -induced liver injury. Pretreatment with diallyl sulfide suppressed CYP2E1 and abolished the circadian rhythmicity of susceptibility to CCl 4 . These findings provide additional support for acetone's physiological role in CYP2E1 induction and for CYP2E1's role in modulating CCl 4 chronotoxicity in rats.Many physiological and biochemical processes in laboratory animals and humans have been found to vary rhythmically over a 24-h period (i.e., to exhibit a circadian or diurnal rhythm). Rhythms are considered as sequences of biological events, repeating themselves in the same order and at the same intervals. Temporal differences in drug action and toxicity have been recognized for over 50 years in humans and in laboratory animals. A number of cyclic physiological processes can affect the absorption, distribution, metabolism, and elimination of drugs and other chemicals (Labrecque and Belanger, 1991).The chronotoxicity of solvents and other industrial chemicals has received relatively little attention. Volatile organic compounds (VOCs) are a class of solvents to which many people are exposed occupationally and environmentally. Early studies of chloroform (Lavigne et al., 1983), carbon tetrachloride (CCl 4 ) (Harris and Anders, 1980;Bruckner et al., 1984), and 1,1-dichloroethylene (Jaeger et al., 1973) revealed circadian rhythms in susceptibility of rats to liver damage by the chemicals. Some of the investigators speculated that periods of enhanced susceptibility might be due to cyclic increases in metabolic activation of the VOCs. Tempora...

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“…Thus, we think that serum concentrations of PBDEs may not reflect a biologically important long-term dose. Furthermore, toxicological studies have shown that different exposure routes led to different pharmacokinetics in terms of uptake, distribution, and elimination (17).…”

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confidence: 99%

Association of Brominated Flame Retardants With Diabetes and Metabolic Syndrome in the U.S. Population, 2003–2004

2008

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OBJECTIVE —Chlorinated persistent organic pollutants (POPs), endocrine disruptors accumulated in adipose tissue, were associated with diabetes and metabolic syndrome. Brominated flame retardants (BFRs), such as polybrominated diphenyl ethers (PBDEs) or polybrominated biphenyls (PBBs), are another class of POPs for which body burden is increasing. Cross-sectional associations of serum concentrations of BFRs with diabetes and metabolic syndrome were studied. RESEARCH DESIGN AND METHODS —In the National Health and Nutrition Examination Survey 2003–2004, 1,367 adults were examined with respect to diabetes status. Five PBDEs and one PBB were selected, detectable in ≥60% of participants. For the outcome metabolic syndrome, we restricted the analysis to 637 participants with a morning fasting sample. RESULTS —Compared with subjects with serum concentrations below the limit of detection, prevalent diabetes had differing dose-response associations with serum concentrations of PBB-153 and PBDE-153. Adjusted odds ratios across quartiles of serum concentrations for PBB-153 or PBDE-153 were 1.0, 0.7, 1.4, 1.6, and 1.9 ( P for trend <0.01) and 1.0, 1.6, 2.6, 2.7, and 1.8 ( P for quadratic term <0.01), respectively. PBB-153 was also positively associated with the prevalence of metabolic syndrome with adjusted odds ratios of 1.0, 1.5, 3.1, 3.1, and 3.1 ( P for trend<0.01). As in its association with diabetes, PBDE-153 showed an inverted U-shaped association with metabolic syndrome. CONCLUSIONS —Pending confirmation in prospective studies, lipophilic xenobiotics, including brominated POPs stored in adipose tissue, may be involved in the pathogenesis of diabetes and metabolic syndrome.

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Uptake, Distribution, and Elimination of Carbon Tetrachloride in Rat Tissues Following Inhalation and Ingestion Exposures

Cited by 68 publications

References 23 publications

A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats.

A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats.

Mechanisms of Circadian Rhythmicity of Carbon Tetrachloride Hepatotoxicity

Association of Brominated Flame Retardants With Diabetes and Metabolic Syndrome in the U.S. Population, 2003–2004

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