Effects of rifampin on CYP2E1-dependent hepatotoxicity of isoniazid in rats

Yue, Jiang; Peng, Rui; Chen, Jie; Liu, Yinghui; Dong, Guicheng

doi:10.1016/j.phrs.2008.10.006

Cited by 38 publications

(32 citation statements)

References 40 publications

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“…The results in Table 1 indicate that none of the isatin-isoniazid derivatives produced hepatotoxicity when given at two nontoxic isoniazid dose levels. Another known property of isoniazid is its ability to increase CYP2E1 activity [Madan et al, 2003;Poloyac et al, 2004;Yue et al, 2004Yue et al, , 2009Zand et al, 1993], an effect that can seriously exacerbate liver toxicity in patients also taking acetaminophen, since this is a major enzyme responsible for converting this drug to its reactive hepatotoxic intermediate (N-acetyl-p-benzoquinoneimine) [Chen et al, 1998;Das et al, 2010;Laine et al, 2009;Manyike et al, 2000;Murphy et al, 1990]. The results displayed in Table 2 show that none of the isatin-isoniazid derivatives increased CYP2E1 activity to a significant level.…”

Section: Discussionmentioning

confidence: 99%

Effects of isatin‐isoniazid derivatives on drug metabolizing and chemoprotective enzymes in mice

El‐Sayed

Aboul‐Fadl

Franklin

2010

Drug Development Research

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Four isatin-isoniazid derivatives with proven efficacy against resistant strains of Mycobacterium tuberculosis, that had greater lipophilicity than isoniazid were evaluated for effects on hepatic drug metabolizing and chemoprotective enzymes and compared to isoniazid. Following intragastric administration to mice (75 or 150 mg/kg Â 3 days), none of the four compounds exhibited hepatotoxicity, and only isoniazid was found to elevate CYP2E1 activity. All compounds slightly elevated Cyp1a1/2 mRNA levels, but these did not result in increased methoxyresorufin demethylase activity. With the exception of isoniazid, approximately twofold elevations in Ugt1a mRNAs (seen with isatin-isoniazid [Ugt1a1, Ugt1a6, Ugt1a9], 1-propynylisatin-isoniazid [Ugt1a1, Ugt1a9], and 1-propylisatin-isoniazid [Ugt1a1]) also did not result in changes in 4-nitrophenol glucuronidation activity. 1-Benzylisatin-isoniazid was the only compound that (1) elevated Ugt2b5 mRNA, and (2) like isoniazid, had no effect on glutathione transferase activities and mRNAs. 1-Propynylisatin-isoniazid elevated glutathione transferase activity toward 1-chloro-2,4-dinitrobenzene, 1-propylisatin-isoniazid decreased the 2.4-kb Gstp transcript, and isatin-isoniazid increased Gsta, Gstm, and the 1.2-kb Gstp transcripts. None of the four compounds affected glutathione peroxidase activity, although 1-propynylisatin-isoniazid and 1-benzylisatin-isoniazid elevated mRNA transcripts. None of the four compounds affected microsomal epoxide hydrolase or thioredoxin reductase activities but, in parallel, isoniazid, 1-propynylisatin-isoniazid, and 1-propylisatin-isoniazid elevated mRNAs of each. 1-Propynylisatin-isoniazid, 1-propylisatin-isoniazid, and 1-benzylisatin-isoniazid, and isoniazid, elevated quinone oxidoreductase (Nqo1) mRNA, but only 1-propylisatin-isoniazid elevated the activity. Altogether, and despite some changes in mRNA expression, the novel isatin-isoniazid derivatives had only minor effects on mouse hepatic enzyme activities and are worthy of further investigation as possible therapeutic agents likely free of major induction-related drug-drug interactions. Drug Dev Res 71:313-322, 2010.

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Section: Discussionmentioning

confidence: 99%

Effects of isatin‐isoniazid derivatives on drug metabolizing and chemoprotective enzymes in mice

El‐Sayed

Aboul‐Fadl

Franklin

2010

Drug Development Research

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“…It was indicated that the C2 carrier genotypes of CYP2E1 RsaI/ PstI polymorphism might be a protective factor which decreased the risk of bladder cancer. The bladder was prone to expose under carcinogens which were known to induce DNA strand breaks in the bladder epithelium cell due to being the urine collecting area (Johansson et al, 1990;Hoeijmakers, 2001;Yue et al, 2009). The CYP2E1 played an important role in the metabolic activation of low molecular weight compounds and pro-carcinogens such as benzene, N-nitrosamines, and halogenated hydrocarbons, which might be involved in bladder cancer development (Guengerich et al, 1991;Yamazaki et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…The major environmental factors included tobacco smoking and occupational exposures (Clapp et al, 2008;Strope and Montie, 2008), which could cause DNA damage, such as cross-links, bulky adducts and single or double strand breaks resulting in unregulated cell growth and even cancer (Johansson et al, 1990;Hoeijmakers, 2001;Yue et al, 2009). Nevertheless, only a small proportion of the individuals exposed to these environmental factors eventually developed bladder cancer, indicating that host genetic factors may play an important role in bladder carcinogenesis (Taioli and Raimondi, 2005 particularly the cytochrome P450 2E1 (CYP2E1), and its polymorphisms might be associated with bladder cancer risk (Gonzalez, 2005).…”

Section: Introductionmentioning

confidence: 99%

Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

Deng

Gao²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. Method: To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. Results: When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk

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“…Rifampin (RMP) and Isoniazid (INH) are the two most potent first line antibiotics that are used in combination to treat tuberculosis [110, 111]. While an acute overdose of anti-TB drugs leads to neurotoxicity, chronic therapeutic treatment is the most common cause of liver injury [112, 113].…”

Section: Rifampin and Isoniazid Hepatotoxicitymentioning

confidence: 99%

“…RMP is bio-activated and detoxified in the liver [110, 111]. Rifampin particularly induces many drug metabolizing enzymes such as CYP1A2, 2C9, 2C19 and 3A4 and therefore increases chances of liver injury caused by additional anti-TB drugs [110] as well as other drugs like APAP [119].…”

Section: Rifampin and Isoniazid Hepatotoxicitymentioning

confidence: 99%

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

et al. 2018

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Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area.

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Effects of rifampin on CYP2E1-dependent hepatotoxicity of isoniazid in rats

Cited by 38 publications

References 40 publications

Effects of isatin‐isoniazid derivatives on drug metabolizing and chemoprotective enzymes in mice

Effects of isatin‐isoniazid derivatives on drug metabolizing and chemoprotective enzymes in mice

Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

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