Effect of dosing vehicles on the pharmacokinetics of orally administered carbon tetrachloride in rats

Kim, H.J.; Bruckner, James V.; Dallas, Cham E.; Gallo, James M.

doi:10.1016/0041-008x(90)90082-6

Cited by 66 publications

(32 citation statements)

References 18 publications

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“…It is particularly toxic to the liver, where it causes hepatocellular degeneration, centrilobular necrosis 1,2 and impairs different enzymatic systems. 3 The generation of free radicals appears to be pivotal in CCl 4 hepatotoxicity: CCl 4 is metabolized by cytochrome P-450 to produce the trichloromethyl radical, which initiates a cascade of free radical reactions resulting in an increase of lipid peroxidation and a reduction in some enzyme activities.…”

Section: Introductionmentioning

confidence: 99%

Oxidative preconditioning affords protection against carbon tetrachloride‐induced glycogen depletion and oxidative stress in rats

Candelario‐Jalil

Mohammed-Al-Dalain

Fernández

et al. 2001

J of Applied Toxicology

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The rectal insufflation of a judicious dose of ozone, selected from that used in clinical practice, is able to promote oxidative preconditioning or oxidative stress tolerance preventing the hepatocellular damage mediated by free radicals. In order to evaluate the effects of ozone oxidative preconditioning on carbon tetrachloride-mediated hepatotoxicity, the following experimental protocol was designed: group 1 (negative control, sunflower oil i.p.); group 2 (CCl(4) in sunflower oil, 1 ml kg(-1) i.p.); group 3 (15 ozone-oxygen pretreatments at a dose of 1 mg kg(-1) via rectal insufflation + CCl(4) as in group 2); group 4 (ozone control group, 15 ozone-oxygen pretreatments + sunflower oil i.p.). Ozone pretreatment prevented glycogen depletion (as demonstrated by biochemical and histopathological findings) and avoided lactate overproduction associated with the hepatotoxic effects of CCl(4). The administration of CCl(4) increased lipid peroxidation (as measured by thiobarbituric acid-reactive substances) and uric acid levels and inhibited superoxide dismutase activity. All these deleterious effects induced by CCl(4) were prevented by ozone pretreatment. The administration of ozone without CCl(4) (ozone control group) did not produce any changes in the evaluated parameters. Our results showed that ozone treatment, in our experimental conditions, was able to prevent anaerobic glycolysis and oxidative stress induced by CCl(4).

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Section: Introductionmentioning

confidence: 99%

Oxidative preconditioning affords protection against carbon tetrachloride‐induced glycogen depletion and oxidative stress in rats

Candelario‐Jalil

Mohammed-Al-Dalain

Fernández

et al. 2001

J of Applied Toxicology

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“…Carbon tetrachloride (CCl 4 ) causes hepatocellular degeneration and centrilobular necrosis (8,9) and impairs different enzymatic systems (10). It is metabolized in the liver by cytochrome P-450 to produce trichloromethyl radicals.…”

Section: Introductionmentioning

confidence: 99%

The Gallic Acid–Phospholipid Complex Improved the Antioxidant Potential of Gallic Acid by Enhancing Its Bioavailability

et al. 2013

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Abstract. Gallic acid (GA) is well known for its antioxidant and hepatoprotective activity, though its effectiveness is restricted due to rapid metabolism and elimination. To overcome these problems, gallic acid-phospholipid complex was prepared and the effect of phospholipid complexation was investigated on carbon tetrachloride (CCl 4 )-induced oxidative damage in rat liver. The complex significantly reduced the hepatic marker enzymes in rat serum and restored the antioxidant enzyme levels with respect to CCl 4 -induced group (P<0.05 and P<0.01). Also, the complex improved the pharmacokinetics of GA by increasing the relative bioavailability and elimination half-life. The study therefore suggests that phospholipid complexation has enhanced the therapeutic efficacy of GA which may be due to its improved absorption and increased bioavailability in rat serum.

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“…CCL, and most other VOCs are small, uncharged lipophilic molecules, which move very rapidly across cell membranes by passive diffusion. Kim et al (1990b) reported similar T^, C^,, AT a , AUC, and bioavailability values for groups of rats given CC1 4 in water and as a 0.25% Emulphor emulsion. The results of the current study of much higher concentrations of Emulphor are quite similar.…”

Section: Discussionmentioning

confidence: 54%

“…We have utilized this agent to produce stable, uniform aqueous emulsions of a number of halocarbons for pharmacokinetic and toxicology studies. Kim et al (1990b) found that the pharmacokinetics of CCLt in rats gavaged with 25 mg CCLj/kg bw was similar whether the chemical was dissolved in water or in 0.25% Emulphor. For higher doses of VOCs, it has been necessary to use increased concentrations of Emulphor.…”

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confidence: 99%

Effect of Emulphor, an Emulsifier, on the Pharmacokinetics and Hepatotoxicity of Oral Carbon Tetrachloride in the Rat

SANZGIRI¹,

BRUCKNER²

1997

Toxicol Sci

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Emulphor, a polyethoxylated vegetable oil, is now being used widely to incorporate volatile organic compounds (VOCs) and other lipophilic compounds into aqueous solutions for biochemical, pharmacokinetic, and toxicological studies. Previous work in this laboratory demonstrated that 0.25% Emulphor did not alter the kinetics or hepatotoxicity of low doses of CCL, compared to when the halocarbon was given to rats orally in water. The present study was undertaken as there was concern that higher concentrations of Emulphor (necessary to maintain lipophilic VOCs in stable aqueous emulsions for extended periods) might alter the VOCs' absorption, disposition, and/or toxidty. Dosages of 10 and 180 mg CCU/kg bw were given, as an aqueous emulsion using 1, 2.5, 5, or 10% Emulphor, by gavage to fasted male Sprague-Dawley rats. Serial microsamples of blood were collected from an indwelling cannula in unanesthetized, freely moving rats at intervals of 2-60 min for up to 12 hr. The samples' CCL, content was measured by headspace gas chromatography. Thereby, it was possible to obtain blood CCL, concentration-versus-time profiles. Animals were euthanized 24 hr postdosing and blood was collected for measurement of serum enzymes as indices of hepatotoxicity. No toxicologically significant differences in pharmacokinetic parameters as a function of Emulphor concentration were found. Similarly the hepatotoxic potency of 10 and 180 mg/kg CCL,, as reflected by elevation in serum enzyme activities, did not vary significantly with the concentration of Emulphor utilized. Hence, it can be concluded that Emulphor, in concentrations as high as 10% (equivalent to 260 mg Emulphor/kg bw) in aqueous emulsions, does not significantly affect the absorption, disposition, or acute hepatotoxicity of CCL, in male Sprague-Dawley rats, o iw sod«y of To

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Effect of dosing vehicles on the pharmacokinetics of orally administered carbon tetrachloride in rats

Cited by 66 publications

References 18 publications

Oxidative preconditioning affords protection against carbon tetrachloride‐induced glycogen depletion and oxidative stress in rats

Oxidative preconditioning affords protection against carbon tetrachloride‐induced glycogen depletion and oxidative stress in rats

The Gallic Acid–Phospholipid Complex Improved the Antioxidant Potential of Gallic Acid by Enhancing Its Bioavailability

Effect of Emulphor, an Emulsifier, on the Pharmacokinetics and Hepatotoxicity of Oral Carbon Tetrachloride in the Rat

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