The Radioprotective Effect of Procaine and Procaine-Derived Product Gerovital H3 in Lymphocytes from Young and Aged Individuals.

Ionizing radiation induces genomic instability in living organisms, and several studies reported an ageing-dependent radiosensitivity. Chemical compounds, such as scavengers, radioprotectors, and modifiers, contribute to reducing the radiation-associated toxicity. These compounds are often antioxidants, and therefore, in order to be effective, they must be present before or during exposure to radiation. However, not all antioxidants provide radioprotection. In this study, we investigated the effects of procaine and of a procaine-based product Gerovital H3 (GH3) on the formation of endogenous and X-ray-induced DNA strand breaks in peripheral blood mononuclear cells (PBMCs) isolated from young and elderly individuals. Interestingly, GH3 showed the strongest radioprotective effects in PBMCs from young subjects, while procaine reduced the endogenous amount of DNA strand breaks more pronounced in aged individuals. Both procaine and GH3 inhibited lipid peroxidation, but procaine was more effective in inhibiting mitochondria free radicals' generation, while GH3 showed a higher antioxidant action on macrophage-induced low-density lipoprotein oxidation. Our findings provide new insights into the mechanisms underlying the distinct effects of procaine and GH3 on DNA damage.

Modulation of Sex Pheromone Discrimination by A UDP-Glycosyltransferase in Drosophila melanogaster.

The detection and processing of chemical stimuli involve coordinated neuronal networks that process sensory information. This allows animals, such as the model species Drosophila melanogaster, to detect food sources and to choose a potential mate. In peripheral olfactory tissues, several classes of proteins are acting to modulate the detection of chemosensory signals. This includes odorant-binding proteins together with odorant-degrading enzymes (ODEs). These enzymes, which primarily act to eliminate toxic compounds from the whole organism also modulate chemodetection. ODEs are thought to neutralize the stimulus molecule concurrently to its detection, avoiding receptor saturation thus allowing chemosensory neurons to respond to the next stimulus. Here, we show that one UDP-glycosyltransferase (UGT36E1) expressed in D. melanogaster antennal olfactory sensory neurons (OSNs) is involved in sex pheromone discrimination. UGT36E1 overexpression caused by an insertion mutation affected male behavioral ability to discriminate sex pheromones while it increased OSN electrophysiological activity to male pheromones. Reciprocally, the decreased expression of UGT36E1, controlled by an RNAi transgene, improved male ability to discriminate sex pheromones whereas it decreased electrophysiological activity in the relevant OSNs. When we combined the two genotypes (mutation and RNAi), we restored wild-type-like levels both for the behavioral discrimination and UGT36E1 expression. Taken together, our results strongly suggest that this UGT plays a pivotal role in Drosophila pheromonal detection.

P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells.

Resveratrol has been proposed to prevent tumor growth and the different steps of carcinogenesis; nevertheless, these biological effects are sometimes discordant between different cell types. Several hypotheses and works have suggested that the metabolism of resveratrol could be at the origin of a different cellular response. We show here, using colorectal tumor cell lines, that the biological effects of RSV result mainly from its carriage by carriers of the superfamily of ABC transporter, i.e., P-gP, MRP, or BCRP. Using cell lines overexpressing these different transporters, we have been able to highlight the importance of P-gP in the response of cells to RSV. These results were confirmed by invalidating the gene coding for P-gP, which restored the sensitivity of colorectal cells resistant to the polyphenol. Subsequently, the status of P-glycoprotein expression is an important element to be taken into consideration in the cytotoxic activity of resveratrol in colorectal cancer cells.

Characterization of rat glutathione transferases in olfactory epithelium and mucus.

The olfactory epithelium is continuously exposed to exogenous chemicals, including odorants. During the past decade, the enzymes surrounding the olfactory receptors have been shown to make an important contribution to the process of olfaction. Mammalian xenobiotic metabolizing enzymes, such as cytochrome P450, esterases and glutathione transferases (GSTs), have been shown to participate in odorant clearance from the olfactory receptor environment, consequently contributing to the maintenance of sensitivity toward odorants. GSTs have previously been shown to be involved in numerous physiological processes, including detoxification, steroid hormone biosynthesis, and amino acid catabolism. These enzymes ensure either the capture or the glutathione conjugation of a large number of ligands. Using a multi-technique approach (proteomic, immunocytochemistry and activity assays), our results indicate that GSTs play an important role in the rat olfactory process. First, proteomic analysis demonstrated the presence of different putative odorant metabolizing enzymes, including different GSTs, in the rat nasal mucus. Second, GST expression was investigated in situ in rat olfactory tissues using immunohistochemical methods. Third, the activity of the main GST (GSTM2) odorant was studied with in vitro experiments. Recombinant GSTM2 was used to screen a set of odorants and characterize the nature of its interaction with the odorants. Our results support a significant role of GSTs in the modulation of odorant availability for receptors in the peripheral olfactory process.

Publisher Correction: Nasal mucus glutathione transferase activity and impact on olfactory perception and neonatal behavior.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Nasal mucus glutathione transferase activity and impact on olfactory perception and neonatal behavior.

In olfaction, to preserve the sensitivity of the response, the bioavailability of odor molecules is under the control of odorant-metabolizing enzymes (OMEs) expressed in the olfactory neuroepithelium. Although this enzymatic regulation has been shown to be involved in olfactory receptor activation and perceptual responses, it remains widely underestimated in vertebrates. In particular, the possible activity of OMEs in the nasal mucus, i.e. the aqueous layer that lined the nasal epithelium and forms the interface for airborne odorants to reach the olfactory sensory neurons, is poorly known. Here, we used the well-described model of the mammary pheromone (MP) and behavioral response in rabbit neonates to challenge the function of nasal mucus metabolism in an unprecedented way. First, we showed, in the olfactory epithelium, a rapid glutathione transferase activity toward the MP by ex vivo real-time mass spectrometry (PTR-MS) which supported an activity in the closest vicinity of both the odorants and olfactory receptors. Indeed and second, both the presence and activity of glutathione transferases were evidenced in the nasal mucus of neonates using proteomic and HPLC analysis respectively. Finally, we strikingly demonstrated that the deregulation of the MP metabolism by in vivo mucus washing modulates the newborn rabbit behavioral responsiveness to the MP. This is a step forward in the demonstration of the critical function of OMEs especially in the mucus, which is at the nasal front line of interaction with odorants and potentially subjected to physiopathological changes.

Data on the expression of GSTE1 and GSTE7 in Drosophila chemosensory organs after isothiocyanate exposure.

The data presented in this article are related to the research article entitled "Characterization of a Drosophila glutathione transferase involved in isothiocyanate detoxification." (Gonzalez et al., 2018) [1]. This article includes the expression level of Drosophila melanogaster GSTE1 and GSTE7 in chemosensory male tissues and the expression level of the mRNAs coding for the same enzymes after a PEITC exposure in food.

Characterization of a Drosophila glutathione transferase involved in isothiocyanate detoxification.

Glutathione transferases (GSTs) are ubiquitous key enzymes that catalyse the conjugation of glutathione to xenobiotic compounds in the detoxification process. GSTs have been proposed to play a dual role in the signal termination of insect chemodetection by modifying odorant and tasting molecules and by protecting the chemosensory system. Among the 40 GSTs identified in Drosophila melanogaster, the Delta and Epsilon groups are insect-specific. GSTs Delta and Epsilon may have evolved to serve in detoxification, and have been associated with insecticide resistance. Here, we report the heterologous expression and purification of the D. melanogaster GST Delta 2 (GSTD2). We investigated the capacity of GSTD2 to bind tasting molecules. Among them, we found that isothiocyanates (ITC), insecticidal compounds naturally present in cruciferous plant and perceived as bitter, are good substrates for GSTD2. The X-ray structure of GSTD2 was solved, showing the absence of the classical Ser catalytic residue, conserved in the Delta and Epsilon GSTs. Using molecular dynamics, the interaction of ITC with the GSTD2 three-dimensional structure is analysed and discussed. These findings allow us to consider a biological role for GSTD2 in chemoperception, considering GSTD2 expression in the chemosensory organs and the potential consequences of insect exposure to ITC.

Odorant-odorant metabolic interaction, a novel actor in olfactory perception and behavioral responsiveness.

In the nasal olfactory epithelium, olfactory metabolic enzymes ensure odorant clearance from the olfactory receptor environment. This biotransformation of odorants into deactivated polar metabolites is critical to maintaining peripheral sensitivity and perception. Olfactory stimuli consist of complex mixtures of odorants, so binding interactions likely occur at the enzyme level and may impact odor processing. Here, we used the well-described model of mammary pheromone-induced sucking-related behavior in rabbit neonates. It allowed to demonstrate how the presence of different aldehydic odorants efficiently affects the olfactory metabolism of this pheromone (an aldehyde too: 2-methylbut-2-enal). Indeed, according to in vitro and ex vivo measures, this metabolic interaction enhances the pheromone availability in the epithelium. Furthermore, in vivo presentation of the mammary pheromone at subthreshold concentrations efficiently triggers behavioral responsiveness in neonates when the pheromone is in mixture with a metabolic challenger odorant. These findings reveal that the periphery of the olfactory system is the place of metabolic interaction between odorants that may lead, in the context of odor mixture processing, to pertinent signal detection and corresponding behavioral effect.

Odorant Metabolism Analysis by an Automated Ex Vivo Headspace Gas-Chromatography Method.

In the olfactory epithelium (OE), odorant metabolizing enzymes have the dual function of volatile component detoxification and active clearance of odorants from the perireceptor environment to respectively maintain the integrity of the tissues and the sensitivity of the detection. Although emphasized by recent studies, this enzymatic mechanism is poorly documented in mammals. Thus, olfactory metabolism has been characterized mainly in vitro and for a limited number of odorants. The automated ex vivo headspace gas-chromatography method that was developed here was validated to account for odorant olfactory metabolism. This method easily permits the measurement of the fate of an odorant in the OE environment, taking into account the odorant gaseous state and the cellular structure of the tissue, under experimental conditions close to physiological conditions and with a high reproducibility. We confirmed here our previous results showing that a high olfactory metabolizing activity of the mammary pheromone may be necessary to maintain a high level of sensitivity toward this molecule, which is critical for newborn rabbit survival. More generally, the method that is presented here may permit the screening of odorants metabolism alone or in mixture or studying the impact of aging, pathology, polymorphism or inhibitors on odorant metabolism.

Cytochrome P450-dependent metabolism of caffeine in Drosophila melanogaster.

Caffeine (1, 3, 7-trimethylxanthine), an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents). A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs) that were highly overexpressed. Flies treated with metyrapone--an inhibitor of CYP enzymes--showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects.

C-terminal amino acids are essential for human heat shock protein 70 dimerization.

The human inducible heat shock protein 70 (hHsp70), which is involved in several major pathologies, including neurodegenerative disorders and cancer, is a key molecular chaperone and contributes to the proper protein folding and maintenance of a large number of protein structures. Despite its role in disease, the current structural knowledge of hHsp70 is almost exclusively based on its Escherichia coli homolog, DnaK, even though these two proteins only share ~50 % amino acid identity. For the first time, we describe a complete heterologous production and purification strategy that allowed us to obtain a large amount of soluble, full-length, and non-tagged hHsp70. The protein displayed both an ATPase and a refolding activity when combined to the human Hsp40. Multi-angle light scattering and bio-layer interferometry analyses demonstrated the ability of hHsp70 to homodimerize. The role of the C-terminal part of hHsp70 was identified and confirmed by a study of a truncated version of hHsp70 that could neither dimerize nor present refolding activity.

When the nose must remain responsive: glutathione conjugation of the mammary pheromone in the newborn rabbit.

In insects, xenobiotic-metabolizing enzymes were demonstrated to regulate pheromones inactivation, clearing them from the olfactory periphery and keeping receptors ready for stimulation renewal. Here, we investigate whether similar processes could occur in mammals, focusing on the pheromonal communication between female rabbits and their newborns. Lactating rabbits emit in their milk a volatile aldehyde, 2-methylbut-2-enal, that elicits searching-grasping in neonates; called the mammary pheromone (MP), it is critical for pups which are constrained to find nipples within the 5 min of daily nursing. For newborns, it is thus essential to remain sensitive to this odorant during the whole nursing period to display several actions of sucking. Here, we show that the MP is enzymatically conjugated to glutathione in newborn olfactory epithelium (OE), in accordance with the high mRNA expression of glutathione transferases evidenced by quantitative reverse transcription-PCR. This activity in the nose is higher than in the liver and in OE of newborns compared with weanlings (no more responsive to the pheromone). Therefore, the results pinpoint the existence of a high level of MP-glutathione conjugation activity in the OE of young rabbits, especially in the developmental window where the perceptual sensitivity toward the MP is crucial for survival.

Odorant-binding proteins and xenobiotic metabolizing enzymes: implications in olfactory perireceptor events.

At the periphery of the olfactory system, the binding of odorants on olfactory receptors (ORs) is usually thought to be the first level of the perception of smell. However, at this stage, there is evidence that other molecular mechanisms also interfere with this chemoreception by ORs. These perireceptor events are mainly supported by two groups of proteins present in the olfactory nasal mucus or in the nasal epithelium. Odorant-binding proteins (OBPs), the first group of proteins have been investigated for many years. OBPs are small carrier proteins capable of binding odorants with affinities in the micromolar range. Although there is no absolute evidence to support their functional roles in vertebrates, OBPs are good candidates for the transport of inhaled odorants towards the ORs via the nasal mucus. The second group of proteins involves xenobiotic metabolizing enzymes, which are strongly expressed in the olfactory epithelium and supposed to be involved in odorant transformation, degradation, and/or olfactory signal termination. Following an overview of these proteins, this review explores their roles, which are still a matter of debate.

Oral homeostasis disruption by medical plasticizer component bisphenol A in adult male rats.

OBJECTIVES/HYPOTHESIS: Bisphenol A (BPA) is a synthetic estrogen-like chemical mimetic widely used in the manufacture of polycarbonate plastics and epoxy resins found in numerous consumer products including food packaging, medical devices, and dental sealants. Because it is recovered in fluids and it can reach high levels in saliva, this study aimed to evaluate its safety on oral homeostasis by examining its effects on salivary glands, mouth epithelium, water consumption, and salt preference, each parameter being estrogen sensitive. STUDY DESIGN: Randomized controlled trial involving rats. METHODS: A dose-response study was conducted in adult Wistar rats randomized into five groups (n = 12). BPA was administered over 6 weeks via drinking water to obtain daily dose exposures of 0 µg/kg, 5 µg/kg, 50 µg/kg, 5 mg/kg, and 12.5 mg/kg of body weight. To evaluate salt preference, 1% NaCl solution and pure water intakes were measured for 3 days by offering two-bottle choices. The rats were then killed; oral biopsies were done and submandibular glands were removed for histologic and morphometric analysis. RESULTS: According to the dose-response curve, BPA decreased total drinking but increased salt preference, which was inversely proportional to water consumption (Kruskal-Wallis, P < .01). It also causes oral dryness and histologic changes in the acinar structures of the submandibular glands at the lowest doses (Kruskal-Wallis, P < .01). CONCLUSIONS: This study shows that oral exposure to BPA in the rat disrupts thirst and buccal homeostasis and raises questions about the salivary gland secretions.

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

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 OM and assessed the impact of this metabolism on peripheral olfactory responses. Rat OM was found to efficiently metabolize quinoline, coumarin and isoamyl acetate. Quinoline and coumarin are metabolized by CYPs whereas isoamyl acetate is hydrolyzed by carboxylesterases. Electro-olfactogram (EOG) recordings revealed that the hydroxylated metabolites derived from these odorants elicited lower olfactory response amplitudes than the parent molecules. We also observed that glucurono-conjugated derivatives induced no olfactory signal. Furthermore, we demonstrated that the local application of a CYP inhibitor on rat olfactory epithelium increased EOG responses elicited by quinoline and coumarin. Similarly, the application of a carboxylesterase inhibitor increased the EOG response elicited by isoamyl acetate. This increase in EOG amplitude provoked by XME inhibitors is likely due to enhanced olfactory sensory neuron activation in response to odorant accumulation. Taken together, these findings strongly suggest that biotransformation of odorant molecules by enzymes localized to the olfactory mucosa may change the odorant's stimulating properties and may facilitate the clearance of odorants to avoid receptor saturation.

Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes.

The present work reports data regarding effects of an induced oxidative stress on the mainly expressed isoforms of UDP-glucuronosyltransferases (UGTs) in the brain. UGT1A6 and UGT1A7 expression and enzymatic activities toward the 1-naphthol were analyzed in rat cultured astrocytes following the exposure for 48 h to redox-cycling xenobiotic compounds such as quinones and bipyridinium ions. The expression of NADPH:cytochrome P450 reductase and NAD(P)H:quinone oxidoreductase 1 (NQO1) was also investigated. Oxidative stress induced significant deleterious changes in astrocyte morphology, decreased cell viability and inhibited catalytic function of UGTs as a result of protein oxidation. Alternatively, in the surviving impaired astrocytes, oxidative conditions induced a significant overactivity and overexpression of xenobiotic detoxification enzymes, as adaptive response. These effects were significantly prevented by the presence of melatonin, suggesting its direct antioxidant action on reactive oxygen species, reflected further on the glucuronidation activity and transcriptional regulation of both UGT1A6 and UGT1A7. Results show that both catalytic properties of UGTs and the expression of UGT1A6, UGT1A7, NQO1 and NADPH:cytochrome P450 reductase in rat astrocytes are greatly influenced by the pro-oxidative environment. In conclusion, an experimental increase in oxidative cellular status could have both immediate and long term consequences on detoxification enzymatic system activity and expression.

Ciprofibrate regulation of rat hepatic bilirubin glucuronidation and UDP-glucuronosyltransferases expression.

Synthetic fibrates are hypolipidemic drugs known to stimulate hepatic peroxisome proliferation and bilirubin glucuronidation. This study was designed to estimate the effects of ciprofibrate simultaneously on rat hepatic bilirubin glucuronoconjugation and on hepatic expression of UGT1A1, UGT1A2 and UGT1A5, all of which belong to the bilirubin cluster. Hepatic bilirubin glucuronidation activity and UDP-glucuronosyltransferase expression (RT-PCR and Western blotting) were measured after a single-dose ciprofibrate treatment (5 mg/kg by gastric intubation) in 36-h time course experiments. Ciprofibrate regulation of PPARα and UGT1A5 mRNA expression was also investigated in rat hepatocytes. Bilirubin conjugation activity was induced by ciprofibrate, reaching a maximum level (2.4×) 24 h after the treatment. UGT1A1 and UGT1A5 mRNA expression was induced 1.5 times by ciprofibrate, with UGT1A5 reaching the basal level of UGT1A1. Although UGT1A2 mRNA was induced approximately threefold by ciprofibrate, its expression level remained low in comparison with basal or induced levels of UGT1A1 and UGT1A5 mRNA. In the 36-h time course experiment, bilirubin conjugation activity as well as UGT1A5 and PPARα mRNA expression presented a biphasic induction profile. Although a similar level of induction was observed in primary cultured hepatocyte experiments, such biphasic variation was not observed for both UGT1A5 and PPARα, and the induction of UGT1A5 mRNA expression by ciprofibrate required de novo protein synthesis. A single dose of ciprofibrate significantly induces rat liver bilirubin conjugation as well as UGT1A1, UGT1A5 and PPARα expression. The induction mechanism may involve PPARα, at least regarding UGT1A5 regulation.

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

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 protection of the brain, the olfactory epithelium itself and the whole body. These proteins could also have a role in the preservation of the olfactory sensitivity by inactivation and clearance of the excess of odorant molecules from the perireceptor space. The goal of the present study was to increase our understanding of the expression and the localization of transporters in this tissue. For most of the studied transporters, we observed an opposite mRNA expression pattern (RT-PCR) in the olfactory epithelium compared to the liver, which is considered to be the main metabolic organ. Olfactory epithelium mainly expressed efflux transporters (MRP, MDR). However, a similar pattern was observed between the olfactory epithelium and the olfactory bulb. We also demonstrate distinct cellular immunolocalization of the transporters in the olfactory epithelium. As previously reported, Mrp1 was mainly found in the supranuclear portions of supporting cells. In addition, Mrp3 and Mrp5 proteins, which were detected for the first time in olfactory epithelium, were localized to the olfactory neuron layer, while Mdr1 was localized to the capillary endothelium of lymphatic vessels in the subepithelial region. The pattern of expression and the distinct localization of the olfactory transporters showed in this work may highlight on their specific function in the whole olfactory epithelium.

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

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 α, 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.