Effect of pregnenolone-16α-carbonitrile and dexamethasone on acetaminophen-induced hepatotoxicity in mice☆
References (47)
- et al.
Sorbitol dehydrogenase and hepatocellular injury: An experimental and clinical study
Gastroenterology
(1963) - et al.
Species differences in hepatic glutathione depletion, covalent binding and hepatic necrosis after acetaminophen
Life Sci.
(1974) Multiplicity of steroid-inducible cytochromes P-450 in rat liver microsomes
Arch. Biochem. Biophys.
(1988)- et al.
Comparative influences of different PB-type and 3-MC-type polychlorinated biphenyl-induced phenotypes on cytocidal hepatotoxicity of bromobenzene and acetaminophen
Toxicol. Appl. Pharmacol.
(1984) - et al.
Species differences in cytotoxic effects of phenacetin and paracetamol in primary monolayer cultures of hepatocytes
Mutat. Res.
(1986) - et al.
Species variation in the metabolic activation of paracetamol to toxic intermediates: Role of cytochromes P-450 and P-448
Toxicol. Lett.
(1983) - et al.
Potential role of activated macrophages in acetaminophen hepatotoxicity. I. Isolation and characterization of activated macrophages from rat liver
Toxicol. Appl. Pharmacol.
(1986) - et al.
Potential role of activated macrophages in acetaminophen hepatotoxicity. II. Mechanism of macrophage accumulation and activation
Toxicol. Appl. Pharmacol.
(1986) - et al.
In vivo and in vitro hepatotoxicity and metabolism of acetaminophen in Syrian hamsters
Toxicology
(1987) - et al.
Protective effect of pregnenolone-16α-carbonitrile on acetaminophen-induced hepatotoxicity in hamsters
Toxicol. Appl. Pharmacol.
(1991)
Mechanism of action of paracetamol protective agents in mice in vivo
Biochem. Pharmacol.
Comparison of six rabbit liver cytochrome P450 isozymes in formation of a reactive metabolite of acetaminophen
Biochem. Biophys. Res. Commun.
Effect of phenobarbital or pregnenolone 16α-carbonitrile (PCN) pretreatment on acute carbon tetrachloride hepatotoxicity in rats
Biochem. Pharmacol.
Acetaminophen hepatotoxicity
Annu. Rev. Med.
Selective inactivation of mouse liver cytochrome P-450 IIIA by cannabidiol
Mol. Pharmacol.
Liver necrosis from paracetamol
Br. J. Pharmacol. Chemother.
Method for quantitative morphologic analysis of tissues
J. Natl. Cancer Inst.
Metabolism of 14C-acetaminophen in humans and laboratory animals
Evidence that acetaminophen and N-hydroxyacetaminophen form a common arylating intermediate, N-acetyl-p-benzoquinoneimine
Mol. Pharmacol.
N-acetyl-p-benzoquinoneimine: A cytochrome P-450 mediated oxidation product of acetaminophen
Acute liver necrosis following overdose of paracetamol
Br. Med. J.
Species variation in toxication and detoxication of acetaminophen in vivo: A comparative study of biliary and urinary excretion of acetaminophen metabolites
J. Pharmacol. Exp. Ther.
Effect of microsomal enzyme inducers on biliary and urinary excretion of acetaminophen metabolites in rats: Decreased hepatobiliary and increased hepatovascular transport of acetaminophen-glucuronide after microsomal enzyme induction
Drug Metab. Dispos.
Cited by (35)
Activation of GR but not PXR by dexamethasone attenuated acetaminophen hepatotoxicities via Fgf21 induction
2017, ToxicologyCitation Excerpt :NAPQI covalently binds to mitochondrial proteins and triggers mitochondrial dysfunction, ATP depletion, and oxidative stress (Jaeschke et al., 2010a, 2010b). Previous reports showed that glucocorticoid exposure worsened acetaminophen-induced liver injury in vivo (Madhu et al., 1992; Masson et al., 2010). This aggravation of acetaminophen-induced liver injury by DEX is mainly observed at relatively higher doses of DEX exposure, such as 50 mg/kg, and is primarily mediated by transcriptional induction of Cyp3a11 and glutathione depletion.
An updated review on drug-induced cholestasis: Mechanisms and investigation of physicochemical properties and pharmacokinetic parameters
2013, Journal of Pharmaceutical SciencesCitation Excerpt :Drugs that act as nuclear receptor activators (e.g., rifampicin, dexamethasone) can increase the clearance of other drugs or induce the formation of reactive metabolites that can cause hepatotoxicity. For example, acetaminophen liver toxicity was exacerbated by increased Phase I-mediated oxidation to the reactive metabolite N-acetyl-p-benzoquinone-imine by CYP inducers.90,91 Several anticholestatic compounds such as UDCA, phenobarbital, and rifampicin are nuclear receptor agonists, which could explain their anticholestatic properties.
Acute liver toxicity due to methylprednisolone: Consider this diagnosis in the context of autoimmunity
2013, Clinics and Research in Hepatology and GastroenterologyCitation Excerpt :Similar mechanisms of action may be suggested for methylprednisolone or prednisolone, although no experimental proof has been made in mouse or human hepatocytes [27,28]. Dexamethasone could also be a contributing factor for paracetamol-induced hepatitis by reducing the reserves of glutathione and increasing the NADPQI level [29,30]. Other possible toxic or protective roles have been attributed to corticosteroids: increased methotrexate liver toxicity [31], inhibition of hepatocyte regeneration [32], and, conversely, hepatic protection [33].
Phagocytes
2010, Comprehensive Toxicology, Second EditionNuclear receptors as drug targets in cholestasis and drug-induced hepatotoxicity
2010, Pharmacology and TherapeuticsRegulation of nuclear factor-κB, activator protein-1, and glutathione levels by tumor necrosis factor-α and dexamethasone in alveolar epithelial cells
2000, Biochemical PharmacologyCitation Excerpt :Furthermore, it has been shown that the modulation of γ-GCS-HS gene expression by TNF-α and dexamethasone occurs by a mechanism involving c-Jun homodimer [38, 56, 61]. Depletion of liver GSH in mice and inhibition of GSH synthesis by dexamethasone have been observed in rat hepatic cells [73, 74]. Inhaled corticosteroid such as beclomethasone dipropionate decreased erythrocyte GSH levels in patients with asthma [75].
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This work supported by USPHS Grant ES-03192.
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Supported by USPHS Training Grant ES-07079. Current address: Searle Research & Development, 4901 Searle Parkway, Skokie, IL 60077.