Potentiation of CCl4-induced liver injury by ketonic and ketogenic compounds: Role of the CCl4 dose

Pilon, Denis; Brodeur, Jean‐Paul; Plaa, Gàbriel L.

doi:10.1016/0041-008x(88)90260-8

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…These observations on A, MEK, and MiBK potentiation of CCl 4 -induced hepatotoxicity agree with those reported by Pilon et al (1988), where the challenge dose influenced the potentiation in such a way that a smaller amount of potentiator was required for a larger dose of CCI 4 and vice versa. With CHCI 3 , however, MEK and MiBK pretreatment lost their potentiating capacity when a small dose of CHCI 3 was tested.…”

Section: Discussionsupporting

confidence: 90%

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Ketone potentiation of haloalkane‐induced hepato‐ and nephrotoxicity. I. dose‐response relationships

Raymond

Plaa

1995

Journal of Toxicology and Environmental Health

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Carbon tetrachloride (CCl4) induced hepatotoxicity and chloroform (CHCl3) induced nephrotoxicity were evaluated in male Sprague-Dawley rats pretreated with acetone (A), methyl ethyl ketone (MEK), and methyl isobutyl ketone (MiBK). Dose-response relationships for A, MEK, and MiBK potentiation of CCl4-induced hepatotoxicity and CHCl3-induced nephrotoxicity were compared. A, MEK, and MiBK pretreatment at a dosage of 6.8 mmol/kg, given daily for 3 d, markedly potentiated CCl4-induced liver toxicity as indicated by a decrease in the CCl4 ED50 to 3.4, 4.6, and 1.8 mmol/kg, respectively, compared to vehicle-pretreated rats (17.1 mmol/kg). Similarly, pretreatment with these ketones (13.6 mmol/kg) potentiated CHCl3 kidney toxicity but to a lesser degree; CHCl3 ED50 values for vehicle-, A-, MEK-, and MiBK-pretreated rats were 3.4, 1.6, 2.1, and 2.2 mmol/kg, respectively. Our results indicate a potency ranking profile for the potentiation of CCl4 hepatotoxicity of MiBK > A > MEK and of A > MEK > or = MiBK for CHCl3 nephrotoxicity. These dissimilar ranking profiles could be due to differences in mechanisms of action for the two target sites.

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Section: Discussionsupporting

confidence: 90%

“…Several investigators demonstrated that A, MEK, or MiBK exacerbated CCI 4 and CHCI 3 toxicity in rats Charbonneau et al, 1988;Pilon et al, 1988;L. Hewitt et al, 1990;Vezina et al, 1990).…”

Section: Discussionmentioning

confidence: 94%

Ketone potentiation of haloalkane‐induced hepato‐ and nephrotoxicity. I. dose‐response relationships

Raymond

Plaa

1995

Journal of Toxicology and Environmental Health

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“…30,31 OS and ER stress are involved in stress-induced liver injury, 10 greatly reducing the detoxification capacity, seriously affecting the animal's performance, and endangering the poultry industry. 32 During OS, augmenting ROS can cause lipid peroxidation and DNA damage. MDA is the main product of the peroxidation of polyunsaturated fatty acids.…”

Section: ■ Discussionmentioning

confidence: 99%

“…In modern poultry farming, broilers are exposed to a series of stressors, leading to liver injury. , OS and ER stress are involved in stress-induced liver injury, greatly reducing the detoxification capacity, seriously affecting the animal’s performance, and endangering the poultry industry …”

Section: Discussionmentioning

confidence: 99%

Hepatic Proteomics Analysis Reveals Attenuated Endoplasmic Reticulum Stress in Lactiplantibacillus plantarum-Treated Oxidatively Stressed Broilers

Yuan

Liu

Zhao

et al. 2023

J. Agric. Food Chem.

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Endoplasmic reticulum (ER) stress plays important roles in oxidative stress (OS), contributing to liver injury. Lactiplantibacillus plantarum P8 (P8) was reported to regulate broiler OS and the gut microbiota in broilers, but its roles in hepatic ER stress remain unclear. In the present study, the role of P8 in liver OS and ER stress was evaluated, and proteomics was performed to determine the mechanism. Results revealed that P8 treatment decreased liver OS and ER stress in dexamethasone (DEX)-induced oxidatively stressed broilers. Proteomics showed that differentially expressed proteins (DEPs) induced by DEX cover the "cellular response to unfold protein" term. Moreover, the DEPs (GGT5, TXNDC12, and SRM) between DEX-and DEX + P8-treated broilers were related to OS and ER stress and enriched in the glutathione metabolism pathway. RT-qPCR further confirmed the results of proteomics. In conclusion, P8 attenuates hepatic OS and ER stress by regulating GGT5, TXNDC12, SRM, and glutathione metabolism in broilers.

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“…The MED was defined as the smallest dose of a potentiator that was able to produce a statistically significant enhanced response to carbon tetrachloride-induced injury. The results of this study suggested that a given level of liver injury induced by a ketonehaloalkane combination could be evaluated on the basis of the potentiator × hepatotoxicant product (Pilon, Brodeur, and Plaa 1988).…”

Section: Chloroformmentioning

confidence: 99%

Safety Assessment of MIBK (Methyl Isobutyl Ketone)1

Johnson¹

2004

Int J Toxicol

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MIBK (Methyl Isobutyl Ketone) is an aliphatic ketone that functions as both a denaturant and solvent in cosmetic products. Current use in cosmetic products is very limited, but MIBK is reported to be used in one nail correction pen (volume = 3 ml) at a concentration of 21%. The maximum percutaneous absorption rate in guinea pigs is 1.1 µmol/min/cm 2 at 10 to 45 min. Metabolites include 4-hydroxy-4-methyl-2-pentanone (oxidation product) and 4-methyl-2-pentanol (4-MPOL) (reduction product). Values for the serum half-life and total clearance time of MIBK in animals were 66 min and 6 h, respectively. In clinical tests, most of the absorbed MIBK had been eliminated from the body 90 min post exposure. MIBK was not toxic via the oral or dermal route of exposure in acute, short-term, or subchronic animal studies, except that nephrotoxicity was observed in rats dosed with 1 g/kg in a short-term study. MIBK was an ocular and skin irritant in animal tests. Ocular irritation was noted in 12 volunteers exposed to 200 ppm MIBK for 15 min in a clinical test. A depression of the vestibulo-oculomotor reflex was seen with intravenous infusion of MIBK (in an emulsion)at 30 µM/kg/min in female rats. The no-observed-effect level in rats exposed orally to MIBK was 50 mg/kg. Both gross and microscopic evidence of lung damage were reported in acute inhalation toxicity studies in animals. Short-term and subchronic inhalation exposures (as low as 100 ppm) produced effects in the kidney and liver that were species and sex dependent. Dermal doses of 300 or 600 mg/kg for 4 months in rats produced reduced mitotic activity in hair follicles, increased thickness of horny and granular cell layers of the epidermis, a decrease in the number of reactive centers in follicles (spleen), an increase in the number of iron-containing pigments in the area of the red pulp (spleen), and a reduction in the lipid content of the cortical layer of the adrenal glands. Neuropathological changes in the most distal portions of the tibial and ulnar nerves were observed in young adult rats which inhaled 1500 ppm MIBK for up to 5 months. No adverse effects were seen in any other neurological end point by any route of exposure in other studies using rats or other animal species. Clinical tests demonstrated a threshold for MIBK-induced irritation of the lungs at 0.03 to 0.1 mg/L after 1 min of respiration. MIBK was not mutagenic in the Ames test or in a mitotic gene-conversion assay in bacteria. Mammalian mutagenicity test results were also negative in the following assays: mouse lymphoma, unscheduled DNA synthesis, micronucleus, cell transformation, and chromosome damage. MIBK did not induce any treatment-related increases in embryotoxicity or fetal malformations in pregnant Fischer 344 rats or CD-1 mice that inhaled MIBK at concentrations of 300, 1000, or 3000 ppm. There was evidence of treatment-related maternal toxicity only at the highest concentration tested. MIBK applied to the tail of rats daily at doses of 300 or 600 mg/kg for 4 months produced changes in the t...

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Potentiation of CCl4-induced liver injury by ketonic and ketogenic compounds: Role of the CCl4 dose

Cited by 10 publications

References 26 publications

Ketone potentiation of haloalkane‐induced hepato‐ and nephrotoxicity. I. dose‐response relationships

Ketone potentiation of haloalkane‐induced hepato‐ and nephrotoxicity. I. dose‐response relationships

Hepatic Proteomics Analysis Reveals Attenuated Endoplasmic Reticulum Stress in Lactiplantibacillus plantarum-Treated Oxidatively Stressed Broilers

Safety Assessment of MIBK (Methyl Isobutyl Ketone)1

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