Combined Effects of Ethanol and Garlic on Hepatic Ethanol Metabolism in Mice.

Kishimoto, Ritsuko; Ueda, Miwa; Yoshinaga, Hideyuki; Goda, Katalin; Park, Song-Shin

doi:10.3177/jnsv.45.275

Cited by 20 publications

(13 citation statements)

References 35 publications

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“…The second stage of ethanol catabolism in the liver, the irre versible oxidation of acetaldehyde to acetate, is cat alyzed by aldehyde dehydrogenase (AlDH). Low Km and high Km AlDH activities were detected in the mitochon dria, microsome, and cytosol fractions of mouse (6,7) and rat (8) liver. It was suggested or reported that low Km mitochondrial A1DH plays the major role in ac etaldehyde metabolism (9).…”

Section: Discussionmentioning

confidence: 99%

Gender-Related Differences in Mouse Hepatic Ethanol Metabolism.

Kishimoto

Ogishi

Ueda

et al. 2002

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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Section: Discussionmentioning

confidence: 99%

Gender-Related Differences in Mouse Hepatic Ethanol Metabolism.

Kishimoto

Ogishi

Ueda

et al. 2002

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

Self Cite

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“…In vivo studies in the mouse indicated that garlic administration increased CYP2E1 and 1A2 levels, although it did not change the total content of hepatic CYP (Kishimoto et al, 1999). However, several studies in the rat indicated that the administration of garlic constituents (e.g., DAD) decreased the CYP2E1 activity and/or protein level, but increased or did not alter the CYP1A, CYP2B, and CYP3A activities and/or protein levels (Dalvi, 1992;Haber et al, 1994;.…”

Section: B Garlicmentioning

confidence: 99%

Interactions of Herbs with Cytochrome P450

Zhou

Gao²,

Jiang

et al. 2003

Drug Metabolism Reviews

357

207

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A resurgence in the use of medical herbs in the Western world, and the co-use of modern and traditional therapies is becoming more common. Thus there is the potential for both pharmacokinetic and pharmacodynamic herb-drug interactions. For example, systems such as the cytochrome P450 (CYP) may be particularly vulnerable to modulation by the multiple active constituents of herbs, as it is well known that the CYPs are subject to induction and inhibition by exposure to a wide variety of xenobiotics. Using in vitro, in silico, and in vivo approaches, many herbs and natural compounds isolated from herbs have been identified as substrates, inhibitors, and/or inducers of various CYP enzymes. For example, St. John's wort is a potent inducer of CYP3A4, which is mediated by activating the orphan pregnane X receptor. It also contains ingredients that inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Many other common medicinal herbs also exhibited inducing or inhibiting effects on the CYP system, with the latter being competitive, noncompetitive, or mechanism-based. It appears that the regulation of CYPs by herbal products is complex, depending on the herb type, their administration dose and route, the target organ and species. Due to the difficulties in identifying the active constituents responsible for the modulation of CYP enzymes, prediction of herb -drug metabolic interactions is difficult. However, herb-CYP interactions may have important clinical and toxicological consequences. For example, induction of CYP3A4 by St. John's wort may partly provide an explanation for the enhanced plasma clearance of a number of drugs, such as cyclosporine and innadivir, which are known substrates of CYP3A4, although other mechanisms including modulation of gastric absorption and drug transporters cannot be ruled out. In contrast, many organosulfur compounds, such as diallyl sulfide from garlic, are potent inhibitors of CYP2E1; this may provide an explanation for garlic's chemoproventive effects, as many mutagens require activation by CYP2E1. Therefore, known or potential herb -CYP interactions exist, and further studies on their clinical and toxicological roles are warranted. Given that increasing numbers of people are exposed to a number of herbal preparations that contain many constituents with potential of CYP modulation, high-throughput screening assays should be developed to explore herb-CYP interactions.Key Words: Herb; Cytochrome P450; Drug interactions.Abbreviations: Ah, aryl hydrocarbon; AUC, the area of the plasma concentrationtime curve; B[a]P, benzo[a]pyrene; C max , the maximum plasma concentration; CL int , intrinsic clearance; CYP, cytochrome P450; DAD, diallyl disulfide; DAS, diallyl sulfide; DASO, diallyl sulfoxide; DASO 2 , diallyl sulfone; DPS, dipropyl sulfide; DPDS, dipropyl disulfide; K i , inhibition constant; K m , Michaelis -Menten constant; NADPH, nicotinamide adenine dinucleotide phosphate; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; N-PiP, N-nitrosopiperidine; PgP, P-glycoprotein; PhIP...

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“…A number of garlic preparations (aged, odourless, oil, freeze-dried) and 3 varieties of fresh garlic bulbs (common, Elephant and Chinese) have been examined for their potential to alter cDNA-expressed human CYP2C9, 2C19, 2D6, 3A4, 3A5 and 3A7 activities using an in vitro fluorometric microtiter plate assay [52]. In vivo studies in the mouse indicated that garlic administration increased CYP2E1 and 1A2 levels, although it did not change the total content of hepatic CYP [53].…”

Section: Pharmacokinetic Mechanismsmentioning

confidence: 99%

Drug-Herb Interactions: Eliminating Toxicity with Hard Drug Design

Yang¹,

Duan³

et al. 2006

CPD

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By searching the literatures, it was found that a total of 32 drugs interacting with herbal medicines in humans. These drugs mainly include anticoagulants (warfarin, aspirin and phenprocoumon), sedatives and antidepressants (midazolam, alprazolam and amitriptyline), oral contraceptives, anti-HIV agents (indinavir, ritonavir and saquinavir), cardiovascular drug (digoxin), immunosuppressants (cyclosporine and tacrolimus) and anticancer drugs (imatinib and irinotecan). Most of them are substrates for cytochrome P450s (CYPs) and/or P-glycoprotein (PgP) and many of which have narrow therapeutic indices. However, several drugs including acetaminophen, carbamazepine, mycophenolic acid, and pravastatin did not interact with herbs. Both pharmacokinetic (e.g. induction of hepatic CYPs and intestinal PgP) and/or pharmacodynamic mechanisms (e.g. synergistic or antagonistic interaction on the same drug target) may be involved in drug-herb interactions, leading of altered drug clearance, response and toxicity. Toxicity arising from drug-herb interactions may be minor, moderate, or even fatal, depending on a number of factors associated with the patients, herbs and drugs. Predicting drug-herb interactions, timely identification of drugs that interact with herbs, and therapeutic drug monitoring may minimize toxic drug-herb interactions. It is likely to predict pharmacokinetic herb-drug interactions by following the pharmacokinetic principles and using proper models that are used for predicting drug-drug interactions. Identification of drugs that interact with herbs can be incorporated into the early stages of drug development. A fourth approach for circumventing toxicity arising from drug-herb interactions is proper design of drugs with minimal potential for herbal interaction. So-called "hard drugs" that are not metabolized by CYPs and not transported by PgP are believed not to interact with herbs due to their unique pharmacokinetic properties. More studies are needed and new approached are required to minimize toxicity arising from drug-herb interactions.

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Combined Effects of Ethanol and Garlic on Hepatic Ethanol Metabolism in Mice.

Cited by 20 publications

References 35 publications

Gender-Related Differences in Mouse Hepatic Ethanol Metabolism.

Gender-Related Differences in Mouse Hepatic Ethanol Metabolism.

Interactions of Herbs with Cytochrome P450

Drug-Herb Interactions: Eliminating Toxicity with Hard Drug Design

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