Assessment of effects of IR and IPC on activities of cytochrome P450 isozymes in rats by a five-drug cocktail approach

Li, Qin; Liu, Ying; Jiao, Jianjie; Zhang, Caili; Jian-shi, Lou

doi:10.3109/03639045.2012.752499

Cited by 2 publications

(3 citation statements)

References 24 publications

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“…In a third rat study, it was shown that the enzymatic activities of CYP1A2, CYP2C9, CYP2E1, CYP2D6, and CYP3A4 were decreased upon liver I/R. [34]…”

Section: Regulation Of Hepatic Drug Metabolism By Liver I/rmentioning

confidence: 99%

Regulation of drug-metabolizing enzymes by local and systemic liver injuries

Guo

Xie

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction Drug metabolism and disposition are critical in maintaining the chemical and functional homeostasis of xenobiotics/drugs and endobiotics. The liver plays an essential role in drug metabolism and disposition due to its abundant expression of drug-metabolizing enzymes (DMEs) and transporters. There is growing evidence to suggest that many hepatic and systemic diseases can affect drug metabolism and disposition by regulating the expression and/or activity of DMEs and transporters in the liver. Areas covered This review focuses on the recent progress on the regulation of DMEs by local and systemic liver injuries. Liver ischemia and reperfusion (I/R) and sepsis are used as examples of local and systemic injury, respectively. The reciprocal effect of the expression and activity of DMEs on animals' sensitivity to local and systemic liver injuries is also discussed. Expert opinion Local and systemic liver injuries have a major effect on the expression and activity of DMEs in the liver. Understanding the disease effect on DMEs is clinically important due to the concern of disease-drug interactions. Future studies are necessary to understand the mechanism by which liver injury regulates DMEs. Human studies are also urgently needed in order to determine whether the results in animals can be replicated in human patients.

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“…In a third rat study, it was shown that the enzymatic activities of CYP1A2, CYP2C9, CYP2E1, CYP2D6, and CYP3A4 were decreased upon liver I/R. [34]…”

Section: Regulation Of Hepatic Drug Metabolism By Liver I/rmentioning

confidence: 99%

Regulation of drug-metabolizing enzymes by local and systemic liver injuries

Guo

Xie

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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“…However, some herbal extracts and phytochemicals have been reported to modulate drug metabolizing enzyme activity, leading to herb-drug interactions which may cause adverse reactions such as toxicity and therapeutic failure [2][3][4] . Among various drug metabolizing enzymes, cytochrome P450 monooxygenase (CYP) is typically involved in clinically significant interactions between prescribed drugs and herbs [5][6][7] . Grapefruit (Citrus paradisi), St. John's wort (Hypericum perforatum), ginkgo (Ginkgo biloba) and licolice (Glycyrrhiza glabra) have all been reported to alter the CYP-mediated metabolism and efficacy of anticoagulants, anticancer drugs, antiretroviral drugs, antihyperlipidemic drugs, immunosuppressants and/or antidepressants [8][9][10][11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

“…Drug Dev Ind Pharm, Early Online:[1][2][3][4][5][6][7] Drug Dev Ind Pharm Downloaded from informahealthcare.com by University of Otago on 07/07/15For personal use only.…”

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confidence: 99%

Metabolic interactions of magnolol with cytochrome P450 enzymes: uncompetitive inhibition of CYP1A and competitive inhibition of CYP2C

Kim

Kang

Cho

et al. 2015

Drug Development and Industrial Pharmacy

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Magnolol (MAG; 5,5'-diallyl-2,2'-biphenyldiol) is a major bioactive component of Magnolia officinalis. We investigated the metabolic interactions of MAG with hepatic cytochrome P450 monooxygenase (CYP) through in vitro microsomal metabolism study using human (HLM) and rat liver microsomes (RLM). CYP2C and 3A subfamilies were significantly involved in the metabolism of MAG, while CYP1A subfamily was not in HLM and RLM. The relative contribution of phase I enzymes including CYP to the metabolism of MAG was comparable to that of uridine diphosphate glucuronosyltransferase (UGT) in RLM. Moreover, MAG potently inhibited the metabolic activity of CYP1A (IC50 of 1.62 μM) and 2C (IC50 of 5.56 μM), while weakly CYP3A (IC50 of 35.0 μM) in HLM and RLM. By the construction of Dixon plot, the inhibition type of MAG on CYP activity in RLM was determined as follows: uncompetitive inhibitor for CYP1A (Ki of 1.09-12.0 μM); competitive inhibitor for CYP2C (Ki of 10.0-15.2 μM) and 3A (Ki of 93.7-183 μM). Based on the comparison of the current IC50 and Ki values with a previously reported liver concentration (about 13 μM) of MAG after its seven times oral administration at a dose of 50 mg/kg in rats, it is suggested that MAG could show significant inhibition of CYP1A and 2C, but not CYP3A, in the in vivo rat system. These results could lead to further studies in clinically significant metabolism-mediated MAG-drug interactions.

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Assessment of effects of IR and IPC on activities of cytochrome P450 isozymes in rats by a five-drug cocktail approach

Abstract: IR can variably decrease the activities of CYP isozymes in rats and this decrease can be attenuated by IPC.

Cited by 2 publications

References 24 publications

Regulation of drug-metabolizing enzymes by local and systemic liver injuries

Regulation of drug-metabolizing enzymes by local and systemic liver injuries

Metabolic interactions of magnolol with cytochrome P450 enzymes: uncompetitive inhibition of CYP1A and competitive inhibition of CYP2C

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