Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction

Guyonnet, Denis; Belloir, Christine; Suschetet, Marc; Siess, Marie‐Hélène; Bon, Anne‐Marie Le

doi:10.1016/s1383-5718(01)00205-4

Cited by 94 publications

(50 citation statements)

References 42 publications

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“…Several investigators have shown that garlic oil or allyl sulfides are able to modulate the enzymatic activities related to xenobiotic metabolisms [29][30][31][32]. Garlic and its constituent(s) have been shown to induce the CYP450 superfamily to near maximal levels except CYP1A subfamily [33], since assaying aryl hydrocarbon hydroxylase is an inducible phenotype of CYP1A1.…”

Section: Discussionmentioning

confidence: 99%

Garlic attenuates chrysotile‐mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system

Ameen

Musthapa

Abidi

et al. 2003

J Biochem & Molecular Tox

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Asbestos and its carcinogenic properties have been extensively documented. Asbestos exposure induces diverse cellular events associated with lung injury. Previously, we have shown that treatment with chrysotile shows significant alteration in phase I and phase II drug metabolizing enzyme system. In this study we have examined some potential mechanisms by which garlic treatment attenuates chrysotile-mediated pulmonary toxicity in rat. Female Wistar rats received an intratracheal instillation of 5 mg chrysotile (0.5 mL saline) as well as intragastric garlic treatment (1% body weight (v/w); 6 days per week). Effect of garlic treatment was evaluated after 1, 15, 30, 90, and 180 days by assaying aryl hydrocarbon hydroxylase (AHH), glutathione (GSH), glutathione S-transferase (GST), and production of thiobarbituric acid reactive substances (TBARS) in rat lung microsome. The results showed that AHH and TBARS formation were significantly reduced at day 90 and day 180 in chrysotile treated garlic cofed rats; GSH recovered 15 days later to the near normal level and GST elevated significantly after treatment of garlic as compared to chrysotile alone treated rat lung microsome. The data obtained shows that inhibition of AHH activity and induction of GST activity could be contributing factor in chrysotile-mediated pulmonary toxicity in garlic cofed rats. However, recovery of GSH and inhibition of TBARS formation by garlic and its constituent(s) showed that garlic may give protection by altering the drug metabolizing enzyme system.

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Section: Discussionmentioning

confidence: 99%

Garlic attenuates chrysotile‐mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system

Ameen

Musthapa

Abidi

et al. 2003

J Biochem & Molecular Tox

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“…In contrast, S9 from DAD-treated rats significantly inhibited the mutagenicity of N-PiP and B[a]P. DAS, DAD, and DPS strongly inhibited imethylnitrosamine mutagenicity, while DPDS enhanced it. The preventive effects of garlic extract on bromobenzene-induced hepatotoxicity in precisioncut liver slices was related to an elevation of hepatic glutathione content, and a glutathione sparing effect, possibly due to conjugation of organosulfur compounds in garlic extract with toxic bromobenzene metabolites (Guyonnet et al, 2001;Wang et al, 1999). Organosulfur compounds also inhibit the formation of DNA adducts in several target tissues.…”

Section: B Association Of Herb -Cyp Interactions With Chemoprotectivmentioning

confidence: 94%

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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“…Any substance that increases the levels or activity of GSTs has a potential to be chemopreventive. Many authors have described the elevation of glutathione S-transferase activity by DAS and DADS administered orally or intraperitoneally [Sheen et al, 1999;Guyonnet et al, 2001]. Fukao et al found that ip administration of DATS (10 lmol/kg of body weigh) to rats caused a marked increase in the activities of glutatione-S-transferase (GST) and quinone reductase (QR) activity, whereas the same doses of DAS and DADS increased the activity of these enzymes only slightly [Fukao et al, 2004].…”

Section: Effect Of Organosulfur Compounds On Detoxification Of Xenobimentioning

confidence: 99%

Biological properties of garlic and garlic‐derived organosulfur compounds

Iciek

Kwiecień

Włodek

2009

Environ and Mol Mutagen

371

270

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Medicinal properties of garlic (Allium sativum) have been widely known and used since ancient times till the present. Garlic enhances immune functions and has antibacterial, antifungal and antivirus activities. It is known to prevent platelet aggregation, and to have hypotensive and cholesterol- and triglyceride-lowering properties, although the latter features have been questioned. This review is focused on anticancer efficacy of Allium sativum, and attempts to explain the mechanisms of this action. Medicinal properties of garlic rely upon organosulfur compounds mostly derived from alliin. Organosulfur compounds originating from garlic inhibit carcinogen activation, boost phase 2 detoxifying processes, cause cell cycle arrest mostly in G2/M phase, stimulate the mitochondrial apoptotic pathway, increase acetylation of histones. Garlic-derived sulfur compounds influence also gap-junctional intercellular communication and participate in the development of multidrug resistance. This review presents also other little known aspects of molecular action of garlic-derived compounds, like modulation of cellular redox state, involvement in signal transduction and post-translational modification of proteins by sulfane sulfur or by formation of mixed disulfides (S-thiolation reactions).

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Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction

Cited by 94 publications

References 42 publications

Garlic attenuates chrysotile‐mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system

Garlic attenuates chrysotile‐mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system

Interactions of Herbs with Cytochrome P450

Biological properties of garlic and garlic‐derived organosulfur compounds

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