Comparison of the chemopreventive efficacies of garlic powders with different alliin contents against aflatoxin B1 carcinogenicity in rats

Garlic (Allium sativum) is well known for its beneficial effects on health and particularly for its chemopreventive potential against cancer. The present study was designed to compare the chemopreventive efficacies of several garlic powders with various levels of alliin, a precursor of active sulfur compounds. For this purpose we used the medium-term hepatocarcinogenesis protocol (resistant hepatocyte model), which allows the detection of preneoplasic foci expressing the placental form of glutathione S-transferase (GST-P) as an end-point. Rats were fed diets containing three garlic powders (5% of the diet) with various alliin contents for 3 weeks. Garlic powders were obtained from bulbs gro…

Olfactory xenobiotic metabolizing enzymes have an impact on the stimulating properties of some odorants

International audience

Use of HepG2 cell line for direct or indirect mutagens screening: comparative investigation between comet and micronucleus assays.

International audience; In the present study, DNA-damage and clastogenic or aneugenic effects of genotoxic compounds were examined in a metabolically competent human cell line (HepG2 cells) using the micronucleus and the comet assays. Compounds with various action mechanisms were tested: direct mutagens such as 4-nitroquinoline-N-oxide (4-NQO) and methyl methanesulfonate (MMS) and indirect mutagens requiring biotransformation to be active such as N-nitrosodimethylamine (NDMA), benzo[a]pyrene (B[a]P) and 2-acetylaminofluorene (2-AAF). The compounds were first tested for cytotoxicity by measuring their effects on RNA synthesis inhibition in HepG2 cells. 4-NQO, B[a]P and 2-AAF were the most po…

Modification of hepatic drug-metabolizing enzymes in rats treated with alkyl sulfides

International audience

In vivo high-throughput identification of olfactory receptor repertoire coding for a blending mixture

International audience

Potential role of flavonoids in cancer prevention

International audience

Enhancement of glutathione transferase activity in rat by dietary administration of flavonoids: organ specificity, dose response and time-course studies

International audience

Flavour: From food to perception

Revue; This book will cover all aspects of flavour perception, including aroma, taste and the role of the trigeminal nerve, from the general composition of food to the perception at the peri-receptor and central level. This book will answer to a growing need for multidisciplinary approaches to better understand the mechanisms involved in flavour perception.The book presents the bases of anatomy of sensory perception. It will provide the requisite basic knowledge on the molecules responsible for flavour perception, on their release from the food matrix during the eating process in order to reach the chemosensory receptors, and on their retention and release from and transformation by bodily …

Unraveling the activation mechanism of olfactory receptors. Towards the future of structure odor relationships

Unraveling the activation mechanism of olfactory receptors. Towards the future of structure odor relationships. 14. Weurman flavour research symposium

Inhibition of ethoxyresorufin deethylase activity by natural flavonoids in human and rat liver microsomes

Several flavones and flavonols (chrysin, quercetin, luteolin, flavone and 7, 8-benzoflavone) were found to inhibit ethoxyresorufin deethylase (EROD) activity in human and rat liver microsomes. In man, molecules without hydroxyl groups are more powerful inhibitors than polyhydroxylated flavonoids (7, 8-benzoflavone greater than flavone greater than chrysin greater than luteolin greater than quercetin greater than morin). In rat, chrysin was the strongest inhibitor and the less effective were morin and 7,8-benzoflavone. For all molecules human microsomes were more sensitive than rat microsomes. The most important difference concerned 7,8-benzoflavone which was 10,000-fold more potent in man.

Activity and expression of drug metabolizing enzymes in olfactory mucosa of rats treated by hepatic inducers

International audience; Several drug-metabolizing enzymes (DME), such as cytochrome P450- dependent monooxygenases (CYP) and transferases have been characterized in the olfactory epithelium. Some of them are preferentially expressed in this tissue, while others are similar to those present in the liver. The role of these enzymes remains unclear. Since the olfactory mucosa is in direct contact with the external environment, these enzymes can contribute to the detoxification of chemical compounds. In addition, these enzymes could be involved in the olfaction process, especially in the biotransformation of odorants. Indeed, the rapid inactivation and clearance of odorants is a prerequisite for…

Glutathione conjugation of the rabbit mammary pheromone 2-methylbut-2-enal

International audience; In the process of smell, the olfactory signal is initiated by the binding of odorous molecules to olfactory receptors. In the receptor environment,associated events are supposed to modulate this signal.Thus, the xenobiotic metabolizing enzymes, potentially involved in the clearance of the odorous molecules, could modulate the availability of these molecules for the olfactory receptors, and consequently could participate indirectly in the olfactory signal termination. A mammary pheromone, which is an odorous aldehyde (2-methylbut-2-enal or 2MB2) has been recently characterized in the rabbit by our group. The aim of this work was to elucidate the metabolism of 2MB2 in …

Effects of garlic powders with varying alliin contents on hepatic drug metabolizing enzymes in rats

International audience; The anticarcinogenic effect of garlic has been demonstrated in both epidemiologic and experimental studies. In this study, possible mechanisms involved in the anticarcinogenic effect of garlic consumption were assessed by determining its capacity to alter drug metabolizing enzymes, in relation with its alliin content. Rats were fed a diet for 2 weeks containing 5% garlic powders produced from bulbs grown on soils with different levels of sulfate fertilization and therefore containing differing amounts of alliin. Activities of several hepatic enzymes, which are important in carcinogen metabolism such cytochromes P450 (CYP) and phase II enzymes, were determined. Garlic…

Perceptual responses to odorant mixtures originate mainly from peripheral processing

International audience

Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats.

International audience; 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 an…

Evidence for multiple interactions at the olfactory receptor level

International audience

Modulation of aflatoxin B1 carcinogenicity, genotoxicity and metabolism in rat liver by dietary carotenoids: evidence for a protective effect of CYP1A inducers

The effects of several carotenoids of vitamin A and of 3-methylcholanthrene have been tested on the initiation of hepatocarcinogenesis by aflatoxin B1, using the sequential protocol of Solt and Farber. AFB1-induced DNA single-strand breaks and AFB1-metabolism were also assessed. The P4501A inducer carotenoids (canthaxanthin, astaxanthin, beta-apo-8'-carotenal) and 3-methylcholanthrene reduce the carcinogenicity of AFB1, divert AFB1-metabolism into the less genotoxic aflatoxin M1 and reduce AFB1-induced DNA single-strand breaks: we conclude that these carotenoids exert their protective effect through the deviation of AFB1 metabolism towards detoxification pathways. beta-Carotene decreased AF…

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

In a previous study, we showed that naturally occurring organosulfur compounds (OSCs) from garlic and onion modulated the activation of carcinogen via the alteration of cytochromes P450. The present study was undertaken to determine the incidence of the in vivo induction of phase II enzymes by individual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on the genotoxicity of carcinogens were evaluated with hepatic cytosols and microsomes from OSCs-treated…

Biotransformation of odorants modifies the olfactory signal

International audience

Les récepteurs olfactifs et le codage des odeurs

The first step of the olfactory detection involves the activation by odorants of olfactory receptors, which are membrane proteins embedded in the membrane of olfactory neurons. Odour coding results from the combinatory activation of a set of receptors and rests on their clonal expression. Neuronal olfactory connexion leads to the formation, in the cortex, of a specific sensory map, which gives rise to the odor perception. This combinatorial system allows, with approximately 340 different receptors, to discriminate myriads of odorants that are natural or not (new cooking flavours, synthetic chemicals…). The extreme olfactory genome diversity in human beings may explain different food behavio…

Impact of diets unbalanced in n-3 polyunsaturated fatty acids on the mouse olfactory function

Périréception et protéines porteuses

ISBN-10 : 978-2-7592-1770-0 ; issn : 1777-4624

Olfactory system in mammals: structural and functional anatomy

Olfactory system in mammals: structural and functional anatomy

Lack of tumor-promoting effects of flavonoids: Studies on rat liver preneoplastic foci and on in vivo and in vitro gap junctional intercellular communication

54 ref.; International audience

UDP-glucuronosyltransferases (UGTs) in neuro-olfactory tissues: expression, regulation, and function.

International audience; This work aims to review uridine diphosphate (UDP)-glucuronosyltransferase (UGT) expression and activities along different neuronal structures involved in the common physiological process of olfaction: olfactory epithelium, olfactory bulb, and olfactory cortex. For the first time, using high-throughput in situ hybridization data generated by the Allen Brain Atlas (ABA), we present quantitative analysis of spatial distribution of UGT genes in the mouse brain. The olfactory area is a central nervous system site with the highest expression of UGTs, including UGT isoforms not previously identified in the brain. Since there is evidence of the transfer of xenobiotics to th…

Potential role flavonoids in cancer prevention

International audience

Different effects of flavonoids on cytochrome P450 3A4- dependent nifedipine oxidation in human liver microsomes

National audience

Interactions at the olfactory receptor level contribute to the coding of odorant mixtures

International audience

Molecular dynamics simulations reveal the active and inactive states of olfactory receptors

Biophysical and functional characterization of the human olfactory receptor OR1A1 expressed in a mammalian inducible cell line

International audience; Olfactory receptors (ORs) play a crucial role in detecting the odorant molecules present in the surrounding environment. These receptors, which belong to class A G-protein-coupled receptors, constitute the largest transmembrane protein family in the human genome. Functional studies showed that the OR family includes members that are able to respond to a large set of odorants and members that are activated by a relatively small number of related odorants. To understand the molecular mechanisms that govern the receptor-ligand interactions, we overexpressed the human OR hOR1A1 in a stable tetracycline-inducible HEK293S cell line. This receptor was engineered by insertin…

Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d'améliorer les paramètres glucido-lipidiques chez la souris obèse

Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d'améliorer les paramètres glucido-lipidiques chez la souris obèse. 30. réunion de l’association française d’étude et de recherche sur l’Obésite (AFERO)

Odorant metabolism catalyzed by olfactory mucosal enzymes influences peripheral olfactory responses in rats.

International audience; A large set of xenobiotic-metabolizing enzymes (XMEs), such as the cytochrome P450 monooxygenases (CYPs), esterases and transferases, are highly expressed in mammalian olfactory mucosa (OM). These enzymes are known to catalyze the biotransformation of exogenous compounds to facilitate elimination. However, the functions of these enzymes in the olfactory epithelium are not clearly understood. In addition to protecting against inhaled toxic compounds, these enzymes could also metabolize odorant molecules, and thus modify their stimulating properties or inactivate them. In the present study, we investigated the in vitro biotransformation of odorant molecules in the rat …

Could aroma compounds interact with the endocannabinoid system?

National audience

The perception of odor objects in everyday life: a review on the processing of odor mixtures

International audience; Smelling monomolecular odors hardly ever occurs in everyday life, and the daily functioning of the sense of smell relies primarily on the processing of complex mixtures of volatiles that are present in the environment (e.g., emanating from food or conspecifics). Such processing allows for the instantaneous recognition and categorization of smells and also for the discrimination of odors among others to extract relevant information and to adapt efficiently in different contexts. The neurophysiological mechanisms underpinning this highly efficient analysis of complex mixtures of odorants is beginning to be unraveled and support the idea that olfaction, as vision and au…

Evidence of interactions between aroma compounds and the CB1 receptor opens new routes for regulation of food intake

Expression and differential localization of xenobiotic transporters in the rat olfactory neuro-epithelium.

International audience; Transporters, such as multidrug resistance P-glycoproteins (MDR), multidrug resistance-related proteins (MRP) and organic anion transporters (OATs), are involved in xenobiotic metabolism, particularly the cellular uptake or efflux of xenobiotics (and endobiotics) or their metabolites. The olfactory epithelium is exposed to both inhaled xenobiotics and those coming from systemic circulation. This tissue has been described as a pathway for xenobiotics to the brain via olfactory perineural space. Thereby, olfactory transporters and xenobiotic metabolizing enzymes, dedicated to the inactivation and the elimination of xenobiotics, have been involved in the toxicological p…

Chemoprevention of hepatocarcinogenesis in rats by diallyl disulphide and dipropyl sulphide : dose-response effect

International audience

Perception du goût : sommes-nous tous égaux ?

National audience; Les sens olfactifs et gustatifs jouent un rôle essentiel dans le comportement alimentaire. L'être humain est capable de percevoir des milliers de composés odorants grâce à un système de codage combinatoire impliquant environ 340 récepteurs olfactifs. Les récepteurs olfactifs sont sujets à un important polymorphisme génétique susceptible d'induire différentes perceptions de certaines odeurs. La perception des molécules sapides implique un nombre beaucoup plus restreint de récepteurs dont certains restent encore à découvrir. Un polymorphisme génétique à l'origine de variations importantes dans les seuils de perception de certains composés sapides affecte également les récep…

In vivo antigenotoxic effects of dietary allyl sulfides in the rat

The effects of dietary administration of diallyl sulfide (DAS), diallyl disulfide (DADS) and allyl mercaptan (AM) on the genotoxicity of different chemicals were studied in two experimental systems: (i) measurement of hepatic DNA single-strand breaks induced in rats by aflatoxin B1 (AFB1), N-nitrosodimethylamine (NDMA) or methylnitrosourea (MNU); (ii) mutagenicity of AFB1 or NDMA on Salmonella typhimurium TA100 using hepatic S9 from rats fed allyl sulfides as the activation system. All compounds strongly reduced hepatic DNA breaks induced by AFB1 and NDMA but did not modify the genotoxicity of MNU. In the Ames test, the mutagenicity of NDMA was strongly inhibited by hepatic S9 from rats fed…

Multidisciplinary approach to explore interactions in odor mixture perception

Odors and aromas perceived in food and in the environment result from the processing of complex chemical mixtures of volatile compounds that should be efficiently processed by the olfactory system. It is known for decades that this processing generates perceptual interactions, such as masking, synergy, or perceptual blending, which contribute to elaborating a synthetic brain representation of the chemical information. Nevertheless, the perceptual processes underlying these interactions are still poorly known. In this project, we set out a multidisciplinary approach to identify the characteristics of odorants and olfactory receptors (ORs) that could support perceptual interactions. We hypoth…

Modulation of phase II enzymes by organosulfur compounds from allium vegetables in rat tissues

International audience

Anticarcinogenic properties of some flavonoids

National audience

Cerveau, sensorialité et métabolisme

The autoradiographic test for unscheduled DNA synthesis: a sensitive assay for the detection of DNA repair in the HepG2 cell line

International audience; We assessed the DNA-repair capacity of HepG2 cells, which were derived from a human hepatoma, by the unscheduled DNA synthesis assay, using the autoradiography protocol (UDS-AR). We evaluated DNA repair following exposure to direct mutagens (4-nitroquinoline-N-oxide (4-NQO), methyl methanesulfonate (MMS)), to mutagens requiring metabolic activation (benzo[a]pyrene (B[a]P), 2-acetylaminofluorene (2-AAF), N-dimethylnitrosoamine (NDMA)) or to structurally related non-mutagens such as pyrene and 4-acetylaminofluorene (4-AAF). All positive compounds tested induced UDS in HepG2 cells. With 4-NQO and MMS, a concentration-dependent increase in net nuclear grains per cell was…

Disease sytems chemical biology of flavors

International audience

Garlic and Cancer

Special Issue; International audience; This review summarizes current knowledge on the anticarcinogenic properties of garlic. Collectively epidemiologic studies – mostly casecontrol studies – provide strong evidence that garlic consumption reduces the risk of cancer especially, the risk of gastric and colon cancer. Furthermore many experimental studies demonstrate that organosulfur compounds (OSCs) and garlic extracts can prevent or slow down the carcinogenic process induced by a variety of chemical carcinogens in animals. Garlic and OSCs have been shown to be active during all the stages of carcinogenesis. Several mechanisms have been proposed to explain the cancer-preventive effects of ga…

The human OR1G1 olfactory receptor is differentially activated by various sandalwood odorants. A joint approach combining in silico and in vitro experiments

International audience; Sandalwood is a highly valuable component in perfumery. The action mode of sandalwood odorant molecules remains to be addressed. In fact, olfactory receptors involved in their perception have not yet been identified. The interaction of a human olfactory receptor, hOR1G1, with sandalwood odorants has been investigated. By means of cellular biology and functional tests experiments, we provide an additional insight to our atomic model of OR1G1 and our olfactophore approach performed on various odorants. The studied odorants cover a wide range of structures and sandalwood intensities. We experimentally show that beta-santalol is a strong agonist of hOR1G1, contrarily to …

Identification of aroma compounds as novel CB1 receptor ligands via in silico approaches

National audience

Mechanisms involved in the chemoprevention of flavonoids

Flavonoids, widespread in edible plants, have been studied extensively for their anticarcinogenic properties. However, only few studies have been done with these constituents being administered by the dietary route. In our research, the effects of feeding rats with flavone, flavanone, tangeretin, and quercetin were investigated on two steps of aflatoxin B1 (AFB1)-induced hepatocarcinogenesis (initiation and promotion). Nonpolar flavonoids such as flavone, flavanone and tangeretin administered through the initiation period, decreased the number of -gamma-glutamyl transpeptidase-preneoplastic foci. In the same conditions of administration, quercetin, a polyhydroxylated flavonoid, showed no pr…

Mécanismes impliqués dans la détection périphérique d'un mélange d'odorants

Chez les mammifères, la première étape de la perception olfactive implique des interactions biochimiques entre les molécules odorantes et les récepteurs olfactifs. La plupart des connaissances sur le fonctionnement du système olfactif repose sur l’utilisation des stimuli simples c’est-à-dire un seul odorant. De ce fait on ignore encore comment le système olfactif reçoit et traite cette information lorsque l’odeur est issue d’un mélange de molécules odorantes. Certaines études suggèrent que les interactions au niveau des récepteurs olfactifs (RO) peuvent affecter fortement la perception des mélanges odorants. La présente étude a pour but d’explorer les phénomènes périphériques qui soustenden…

Perception périphérique des signaux sensoriels. 1- Olfaction

National audience

Organosulfur compounds from Allium and the chemoprevention of cancer

150 ref.; International audience