Gene expression profiling in male B6C3F1 mouse livers exposed to kava identifies – Changes in drug metabolizing genes and potential mechanisms linked to kava toxicity

Guo, Lei; Shi, Qiang; Dial, Stacey L.; Xia, Qingsu; Mei, Nan; Li, Quan Zhen; Chan, Po-Chuen; Fu, Peter P.

doi:10.1016/j.fct.2009.11.050

Cited by 26 publications

(31 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides classes of compounds, such as polycyclic aromatic hydrocarbons, a wide array of substances has been found to induce CYP1A1, including prescription drugs, cigarette smoke, and dietary supplements (Guo et al, 2010b; Li et al, 2011; Ma and Lu, 2007). For instance, we have reported that herbal dietary supplements, such as kava and Gingko biloba, dramatically induce CYP1A1 (Guo et al, 2009; Guo et al, 2010a; Guo et al, 2010c; Li et al, 2011). It may be helpful for the patient administered amiodarone to take precautions to avoid the activation of CYP 1A1 as a result of their use of such dietary supplements or other CYP 1A1 inducers, as this could potentially affect the metabolism of amiodarone and its cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

The role of CYP 3A4 and 1A1 in amiodarone-induced hepatocellular toxicity

Xuan

Ren

et al. 2016

Toxicology Letters

Self Cite

View full text Add to dashboard Cite

Amiodarone is a widely used potent antiarrhythmic for the treatment of cardiac disease; however, its use is often discontinued due to numerous adverse effects, including hepatotoxicity. To investigate the role of drug metabolism in this liver toxicity, amiodarone and its major metabolite desethylamiodarone were incubated with HepG2 cells overexpressing a series of cytochrome P450 (CYP) isoforms. Significantly higher cytotoxicity of amiodarone was observed in HepG2 cells overexpressing CYP3A4 or CYP1A1, compared with that observed in empty vector transduced control cells. Further, higher levels of the more potent hepatotoxic metabolite desethylamiodarone were detected in CYP3A4 or CYP1A1 expressed cells. The CYP3A4 inhibitor ketoconazole and the CYP1A1 inhibitor α-naphthoflavone drastically inhibited the metabolism of amiodarone to desethylamiodarone. Along with the inhibition of CYP1A1 or CYP3A4, the cytotoxicity of amiodarone was significantly reduced. These data indicate that the metabolism of amiodarone to desethylamiodarone by CYP1A1 or CYP3A4 plays an important role in the hepatocellular toxicity of amiodarone.

show abstract

Section: Discussionmentioning

confidence: 99%

The role of CYP 3A4 and 1A1 in amiodarone-induced hepatocellular toxicity

Xuan

Ren

et al. 2016

Toxicology Letters

Self Cite

View full text Add to dashboard Cite

show abstract

“…3), demonstrating that DHM does not inhibit the reductive formation of NNAL from NNK. Results from numerous studies suggest that kavalactones can directly inhibit cytochrome 450 enzymes or indirectly regulate cytochrome 450 enzymes via transcriptional induction (Ma et al, 2004;Zou et al, 2004;Lim et al, 2007;Guo et al, 2010;Li et al, 2011). DHM, one of the major kavalactones, had minimal effect on CYP2A5 enzymatic activity in the mouse liver microsomes at 10 mM.…”

Section: Discussionmentioning

confidence: 99%

Dietary Dihydromethysticin Increases Glucuronidation of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol in A/J Mice, Potentially Enhancing Its Detoxification

Narayanapillai

Carmella

Leitzman

et al. 2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

Effective chemopreventive agents are needed against lung cancer, the leading cause of cancer death. Results from our previous work showed that dietary dihydromethysticin (DHM) effectively blocked initiation of lung tumorigenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice, and it preferentially reduced 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)-derived DNA adducts in lung. This study explored the mechanism(s) responsible for DHM's differential effects on NNK/NNAL-derived DNA damage by quantifying their metabolites in A/J mice. The results showed that dietary DHM had no effect on NNK or NNAL abundance in vivo, indicating that DHM does not affect NNAL formation from NNK. DHM had a minimal effect on cytochrome P450 2A5 (CYP2A5, which catalyzes NNK and NNAL bioactivation in A/J mouse lung), suggesting that it does not inhibit NNAL bioactivation. Dietary DHM significantly increased O-glucuronidated NNAL (NNAL-O-gluc) in A/J mice. Lung and liver microsomes from dietary DHM-treated mice showed enhanced activities for NNAL O-glucuronidation. These results overall support the notion that dietary DHM treatment increases NNAL detoxification, potentially accounting for its chemopreventive efficacy against NNK-induced lung tumorigenesis in A/J mice. The ratio of urinary NNAL-O-gluc and free NNAL may serve as a biomarker to facilitate the clinical evaluation of DHM-based lung cancer chemopreventive agents.

show abstract

“…As expected, the elimination half-life (t 1/2 ) was prolonged by 1.6-fold, while T max and volume of distribution (V ss ) was increased by 2.8-fold (p o0.05) and 2.2-fold, respectively. Recent studies on the molecular mechanisms of traditional Chinese medicinal formulae (Cheng et al, 2010;Cheng et al, 2008;Wen et al, 2011) or herbal extracts (Guo et al, 2010a;Guo et al, 2010b;Guo et al, 2010c) using gene expression microarray have been reported. The results of Guo et al (Guo et al, 2010a) indicated that drug-metabolizing genes were significantly altered in response to Ginkgo Biloba extracts treatments.…”

Section: Discussionmentioning

confidence: 99%