Modification of hepatic drug-metabolizing enzymes in rat fed naturally occurring allyl sulphides

Haber, Dorota; Siess, Marie‐Hélène; Waziers, Isabelle de; Beaune, Philippe; Suschetet, Marc

doi:10.3109/00498259409043230

Cited by 64 publications

(33 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, garlic oil and its three allyl sulfide components administered for 6 weeks have been shown to lead to enhanced activity and increased expression of CYP3A1, 2B1, and 1A1 in the hepatic detoxification system of rats (18). Similarly, in vitro and in vivo animal models have indicated that various garlic constituents used at very high concentrations can induce the activity of the rodent orthologue of CYP3A4 (19).…”

Section: Discussionmentioning

confidence: 99%

Influence of Garlic (Allium sativum) on the Pharmacokinetics of Docetaxel

Cox

Low²,

Lee³

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The herbal supplement garlic (Allium sativum) is commonly used by cancer patients.Preclinical studies have shown that allicin, a major component of garlic, may affect cytochrome P450 3A4 (CYP3A4) activity.This study examines the influence of garlic supplementation on the pharmacokinetics of docetaxel, a CYP3A4 substrate. Experimental Design: Women with metastatic breast cancer were treated with docetaxel (30 mg/m 2 ) given weekly for 3 of 4 weeks. Three days after the initial dose of docetaxel, patients received 600 mg of garlic twice daily for 12 consecutive days. Docetaxel pharmacokinetics were assessed during the first three administrations. Results: In 10 evaluable patients, the mean baseline clearance of docetaxel was 30.8 L/h/m 2 [95% confidence intervals (95% CI), 16.7-44.9]. Coadministration of garlic reduced mean clearance of docetaxel to 23.7 L/h/m 2 (95% CI, 15.5-31.8) and 20.0 L/h/m 2 (95% CI, 13.3-26.7) on days 8 and 15, respectively (P = 0.17). Additional pharmacokinetic variables of docetaxel, including peak concentration (P = 0.79), area under the curve (P = 0.36), volume of distribution (P = 0.84), and half-life (P = 0.36), were also not statistically significantly different. The mean area under the curve ratio between day 15 and day 1 was 3.74 in three individuals with the CYP3A5*1A/*1A genotype (all African American) compared with 1.02 in six individuals with the CYP3A5*3C/*3C genotype (all Caucasian). Conclusions: This study indicates that garlic does not significantly affect the disposition of docetaxel. However, it cannot be excluded that garlic decreases the clearance of docetaxel in patients carrying a CYP3A5*1A allele.

show abstract

Section: Discussionmentioning

confidence: 99%

Influence of Garlic (Allium sativum) on the Pharmacokinetics of Docetaxel

Cox

Low²,

Lee³

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…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;. For example, treatment of rat with DAD increased the activities of CYP2B1/2, but decreased that of the nitrosodimethylamine demethylase (CYP2E1) and the protein level of CYP2E1 in the liver as determined by Western blotting analysis (Haber et al, 1995).…”

Section: B Garlicmentioning

confidence: 99%

“…A single dose of garlic oil in the rat resulted in a significant inhibition of hepatic CYP-catalyzed reactions including aminopyrine N-demethylase (CYP2C) and aniline hydroxylase (CYP2E1) activity, but administration of garlic for five days led to a significant increase in these hepatic CYP activities (Fitzsimmons and Collins, 1997). Short-or long-term administration of rats with garlic constituents (e.g., DAS, DAD, dipropyl sulfide, and diallyl trisulfide) resulted in a decreased activity and expression of CYP2E1, but short-term use usually did not alter the activity and expression of CYP1A and CYP2B (Dalvi, 1992;Haber et al, 1994;. However, long-term administration (e.g., 6 to 7 weeks) led to an enhanced activity and expression of CYP1A and CYP2B1 at mRNA and protein levels (Sheen et al, 1999a,b), except that dipropyl disulfide significantly increased the activity of CYP2E1 (Guyonnet et al, 2000).…”

Section: B Garlicmentioning

confidence: 99%

Interactions of Herbs with Cytochrome P450

Zhou

Gao²,

Jiang

et al. 2003

Drug Metabolism Reviews

358

207

View full text Add to dashboard Cite

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...

show abstract

“…Microsomes and cytosols were prepared by differential centrifugation as described previously (Haber et al, 1994;Minn et al, 2005) and stored in small aliquots at Ϫ80°C. In each group, four pools of four OM were set up to have enough material to perform all of the enzyme assays on the same samples.…”

Section: Modulation Of Olfactory Xenobiotic-metabolizing Enzymesmentioning

confidence: 99%

Effects of Typical Inducers on Olfactory Xenobiotic-Metabolizing Enzyme, Transporter, and Transcription Factor Expression in Rats

Thiebaud¹,

Sigoillot²,

Chevalier³

et al. 2010

Drug Metabolism and Disposition

View full text Add to dashboard Cite

ABSTRACT:Several xenobiotic-metabolizing enzymes (XMEs) have been identified in the olfactory mucosa (OM) of mammals. However, the molecular mechanisms underlying the regulation of these enzymes have been little explored. In particular, information on the expression of the transcriptional factors in this tissue is quite limited. The aim of the present study was to examine the impact of five typical inducers, Aroclor 1254, 3-methylcholanthrene, dexamethasone, phenobarbital, and ethoxyquin, on the activities and mRNA expression of several XMEs in the OM and in the liver of rats. We also evaluated the effects of these treatments on the mRNA expression of transcription factors and transporters. On the whole, the intensities of the effects were lower in the OM than in the liver. Dexamethasone was found to be the most efficient treatment in the OM. Dexamethasone induced the transcription of several olfactory phase I, II, and III genes [such as cytochromes P450 2A3 and 3A9, UDP-glucuronosyltransferase (UGT) 2A1, and multidrug resistance-related protein type 1] and increased UGT activities. We observed that dexamethasone up-regulated sulfotransferase 1C1 expression in the OM but down-regulated it in the liver. Aroclor and ethoxyquin induced the gene expression of CYP1A and quinone reductase, respectively, in the OM. The transcription factors aryl hydrocarbon receptor, nuclear factor E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor ␣, pregnane X receptor, and glucocorticoid receptor were detected in the OM, but no constitutive androstane receptor expression was observed. Dexamethasone and Aroclor enhanced olfactory Nrf2 expression. These results demonstrate that olfactory XME can be modulated by chemicals and that the mechanisms involved in the regulation of these enzymes are tissue-specific.

show abstract

Modification of hepatic drug-metabolizing enzymes in rat fed naturally occurring allyl sulphides

Cited by 64 publications

References 31 publications

Influence of Garlic (Allium sativum) on the Pharmacokinetics of Docetaxel

Influence of Garlic (Allium sativum) on the Pharmacokinetics of Docetaxel

Interactions of Herbs with Cytochrome P450

Effects of Typical Inducers on Olfactory Xenobiotic-Metabolizing Enzyme, Transporter, and Transcription Factor Expression in Rats

Contact Info

Product

Resources

About