Christy J.W. Watson's research while affiliated with Washington State University and other places

Publications (36)

Article
Full-text available
Cannabis-based products have experienced notable increases in co-usage alongside tobacco products. Several cannabinoids exhibit inhibition of a number of cytochrome P450 (CYP) and UDP glucuronosyltransferase (UGT) enzymes, but few studies have examined their inhibition of enzymes involved in nicotine metabolism. The goal of the present study was to...
Article
Introduction Cannabis is an increasingly popular recreational and medicinal drug in the USA. While cannabis is still a Schedule 1 drug federally, many states have lifted the ban on its use. With its increased usage, there is an increased potential for potential drug-drug interactions (DDI) that may occur with concomitant use of cannabis and pharmac...
Article
Full-text available
Background: Nicotine metabolism is a major factor in nicotine dependence, with approximately 70-80% of nicotine metabolized to cotinine in Caucasians. Cotinine formation is catalyzed primarily by CYP2A6, which also converts cotinine to trans-3'-hydroxycotinine (3HC). The goal of the present study was to examine the effects of CYP2A6 deficiency on...
Article
Full-text available
Exemestane (EXE) is an aromatase inhibitor used to treat hormone-dependent breast cancer. EXE is extensively metabolized, with unchanged EXE and its active metabolite 17-dihydroexemestane (17-DHE) accounting for 17 and 12%, respectively, of total plasma EXE in vivo The major circulating EXE metabolites are the cysteine conjugates of EXE and 17-DHE,...
Article
Full-text available
Exemestane (EXE) is used to treat post-menopausal women diagnosed with estrogen receptor positive (ER+) breast cancer. A major mode of metabolism of EXE and its active metabolite, 17β-dihydroexemestane (17β-DHE), is via glutathionylation by glutathione-S-transferase (GST) enzymes. The goal of the present study was to investigate the effects of gene...
Article
Opioids including morphine are mu-opioid receptor (MOR) agonists that suppress excitatory neurotransmitter release, hyperpolarize neuronal cells, and decrease overall excitability, resulting in the desired analgesic effect. As a result of their over-prescription, the still-growing opioid epidemic has devastated many communities, with many individua...
Article
Cannabis and cannabis-derived products are increasingly used for recreational and medical purposes including anxiety and epilepsy and are often concurrently used with other types of conventional medications. The concomitant use of cannabis with other therapeutic drugs has been shown to increase the likelihood of deleterious drug-drug interactions....
Preprint
Full-text available
Background: Exemestane (EXE) is used to treat post-menopausal women diagnosed with estrogen receptor positive (ER+) breast cancer. A major mode of metabolism of EXE and its active metabolite, 17β-dihydroexemestane (17β-DHE), is via glutathionylation by glutathione-S-transferase (GST) enzymes. The goal of the present study was to investigate the eff...
Article
The major mode of metabolism of nicotine is via the formation of cotinine by the enzyme cytochrome P450 (CYP) 2A6. Cotinine undergoes further CYP2A6-mediated metabolism by hydroxylation to 3-hydroxycotinine and norcotinine but can also form cotinine-N-glucuronide and cotinine-N-oxide (COX). The goal of the present study was to investigate the enzym...
Article
Objective To determine if a 2-day protocol measuring pharmacokinetic and pharmacodynamic characteristics can demonstrate drug-drug interactions when smoked cannabis is added to orally administered hydrocodone/acetaminophen combination products. Case Summary A 51-year-old non-Hispanic white male with chronic pain diagnoses participated in a 2-day p...
Article
Exemestane (EXE) is a hormonal therapy used to treat estrogen receptor positive (ER+) breast cancer by inhibiting the final step of estrogen biosynthesis catalyzed by the enzyme aromatase. Cysteine conjugates of EXE and its active metabolite 17β-dihydro-EXE (17β-DHE) are the major metabolites found in both the urine and plasma of patients taking EX...
Article
Full-text available
The legalization of cannabis in many parts of the United States and other countries has led to a need for a more comprehensive understanding of cannabis constituents and their potential for drug-drug interactions. While (-)-trans-Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) are the most abundant cannabinoids present in can...
Article
Full-text available
The UDP-glucuronosyltransferase (UGT) family of enzymes play a central role in the metabolism and detoxification of a wide range of endogenous and exogenous compounds. UGTs exhibit a high degree of structural similarity and display overlapping substrate specificity, often making estimations of potential drug-drug interactions difficult to fully elu...
Article
The UDP-glycosyltransferase (UGT) family of enzymes are important in the metabolism of a variety of exogenous substances including polycyclic aromatic hydrocarbons (PAHs), a potent class of environmental carcinogens. As compared to the majority of UGT enzymes, which utilize UDP-glucuronic acid as a cosubstrate, UGT3A2 utilizes alternative cosubstra...
Article
Full-text available
Cellular stress response mechanisms normally function to enhance survival and allow for cells to return to homeostasis following an adverse event. Cancer cells often co-opt these same mechanisms as a means to evade apoptosis and mitigate a state of constant cellular stress. Activating transcription factor 5 (ATF5) is upregulated under diverse stres...
Article
Full-text available
Bangladesh exhibits the second highest rate of smokeless tobacco (SLT) product usage in the world, and this has been associated with the high upper aerodigestive tract cancer incidence in this country. The goal of the present study was to examine the levels of the highly carcinogenic tobacco-specific nitrosamines (TSNAs) in Bangladeshi SLT products...
Article
Full-text available
The recent legalization of marijuana in many parts of the United States and other countries has led to an increased need for a more comprehensive understanding of the metabolism of marijuana constituents, specifically in regard to potential drug‐drug interactions (DDIs) with cannabinoids and their numerous metabolites. To understand the DDI potenti...
Article
Full-text available
Polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens and are a primary risk factor in the development of lung and other aerodigestive tract cancers in smokers. The detoxification of PAHs by glucuronidation is well-characterized for the UDP-glycosyltransferase (UGT) 1A, 2A, and 2B subfamilies; however, the role of the UGT3A subfamily in PA...
Article
Full-text available
During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by CYP2A6. Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effect...
Article
Full-text available
The UDP-glucuronosyltransferase (UGT) family of enzymes are important in the metabolic elimination of a variety of endogenous compounds such as bile acids, steroids, and fat-soluble vitamins, as well as exogenous compounds including many pharmaceuticals. The UGT2B subfamily are the predominant isoforms expressed in human liver. The identification o...
Conference Paper
ead and neck cancers are among the most common cancers in Southeast Asia and are likely to face sharp increases in the coming years due to the widespread use of smokeless tobacco (SLT) products. Bangladesh has the second highest oral cancer mortality rate as well as the second highest rate of SLT product usage worldwide. SLT products contain high l...
Article
Full-text available
Background: The major mode of metabolism of nicotine is by hydroxylation via cytochrome P450 (CYP) 2A6, but it can also undergo glucuronidation by UDP-glucuronosyltransferases and oxidation by flavin monooxygenases (FMO). The goal of this study was to examine the potential importance of FMOs in nicotine metabolism and assess the potential impact o...
Article
Full-text available
Cigarette smoking causes nearly one in every five deaths in the United States. The development of a specific inhibitor of cytochrome P450 2A6 (CYP2A6), the major nicotine-metabolizing enzyme in humans, which could be prescribed for the cessation of cigarette smoking, has been undertaken. To further refine the structure activity relationship of CYP2...
Article
Full-text available
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most abundant and carcinogenic tobacco-specific nitrosamine in tobacco and tobacco smoke. The major metabolic pathway for NNK is carbonyl reduction to form the (R) and (S) enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) which, like NNK, is a potent lung carcinogen. The...
Article
Full-text available
The UDP-glucuronosyltransferase (UGT) 2B enzymes are important in the detoxification of a variety of endogenous and exogenous compounds including many hormones, drugs and carcinogens. Identifying novel mechanisms governing their expression is important in understanding patient-specific response to drugs and cancer risk factors. In silico prediction...

Citations

... For nicotine metabolite detection, we used a method identical to that described and validated in previous studies. 33 Briefly, nicotine, NOX, Nic-Gluc, HPBA, cotinine, COX, Cot-Gluc, 3HC, and 3HC-Gluc were detected using a UPLC (Waters Acquity; Waters Corp, Milford, MA) coupled to a triple-quadrupole mass spectrometer equipped with a Zspray electrospray ionization interface (Waters Xevo TQD; Waters Corp) by multiple reaction monitoring (MRM). While a nornicotine standard was not available for the present studies, nornicotine was identified using both parent and daughter scans to develop and confirm an MRM method for nornicotine detection. ...
... The human alpha class GSTs subfamily includes five isoenzymes (hGSTA1-1 to hGSTA5-5), whose genes are located on chromosome 6p12.1-6p12.2. The isoenzyme hGSTA1-1 appears to be involved in a wide range of functions [10][11][12][13][14][15][16]. It is expressed at high levels in liver, intestine, kidney, adrenal gland, and testis, and catalyzes the detoxification of a wide range of carcinogenic metabolites and several alkylating chemotherapeutic agents that are used in cancer therapy [10][11][12][13][14][15][16]. ...
... Assay accuracy and precision accuracy were validated on LC-MS/ MS by repeated sample quantification by preparing five individual samples of reaction matrix containing 1 ppm cotinine, COX, or 3HC standard, processing them for LC-MS/MS, and immediately measuring cotinine, COX, or 3HC concentrations for each standard sample as compared to individually prepared standard curves all measured by LC-MS/MS as previously described. 52 The mean recovery for the five samples was >88% while the coefficient of variation (CV) was 3.1% for these samples, suggesting high accuracy and precision for these studies. ...
... Further metabolism of exemestane and 17b-DHE proceeds through the phase II pathways of glutathionylation and glucuronidation. Glutathionylation begins with the conjugation of the tripeptide glutathione (GSH) to EXE or 17b-DHE, primarily via glutathione S-transferase (GST) A1 (Teslenko et al., 2021). Subsequent stepwise removal of the glutamine via c-glutamyl transferase enzymes and the glycine via dipeptidases results in a stable cysteine conjugate (Hinchman and Ballatori, 1994;Hayes et al., 2005;Luo et al., 2018b;Teslenko et al., 2021). ...
... 26 Previous studies have shown that cannabinoids and several major THC metabolites can inhibit several important hepatic CYPs 27,28 as well as UGT enzymes. 29 The goal of the present study was to examine the inhibitory potential of CBD and its major metabolite, 7-OH-CBD, on nicotine metabolic pathways, with the goal of better understanding the potential effect of these cannabinoids on tobacco addiction. ■ EXPERIMENTAL PROCEDURES Chemicals and Reagents. ...
... Nonspecific binding constants (f u,inc ) for CBD in HEK293 microsomes and HLM were determined previously. 29,53 For the f u,inc for 7-OH-CBD, the previously determined f u,inc for the structurally similar 11-OH-THC 53 was used as a surrogate. IC 50 values were determined using the following equation: 50 where "bottom" is the maximum observed inhibition (lowest percent activity), and "top" is the minimum observed inhibition (highest percent activity) for a given cannabinoid. ...
... Nicotine added to most e-liquids is isolated from the tobacco plant, although synthetic tobacco has become available [16]. Tobacco-based nicotine is highly purified and distilled, but trace impurities including nicotine-related alkaloids and tobacco-specific nitrosamines (TSNAs) are impossible to completely remove [17]. TSNAs are known carcinogens. ...
... Reestablishing the expression of miRNAs that are downregulated or specifically omitted in cells is the main goal of the replacement [156,157]. Moreover, restoring miRNA expression can occur via the infection of a viral carrier to stabilize a special miRNA or deliver mature miRNAs known as miRNA mimics, including double-stranded oligonucleotides of nearly 22 nt length, which bear a similar sequence to endogen mature miRNA [158]. In this regard, various types of non-viral delivery systems have been developed, which consist of a lipid-based vehicle, polymeric carrier, functionalized lipid or polymeric nanocarrier, nanovector with a positive, negative or neutral charged and inorganic materials [159,160]. ...
... Several periodontal diseases are linked with the biofilm formation activity of the oral pathogens in presence of nicotine (Wu et al. 2018;El-Ezmerli and Gregory 2019). Exposure to nicotine has been reported to promote the growth as well as biofilm formation activity of several pathogens (Huang et al. 2012;Nasrin et al. 2020;Vishwakarma and Verma, 2021). However, up to 8 to 16, mg/ml of nicotine concentration supports the growth as well as biofilm formation in the majority of the bacteria, thereafter it inhibits nicotineinduced-biofilm formation (DuBois et al. 2014). ...
... Previous studies have shown that THC, CBD, and CBN can strongly inhibit several major hepatic CYPs (Yamaori et al., 2010;Yamaori et al., 2011a;Yamaori et al., 2011b;Yamaori et al., 2011c;Jiang et al., 2013;Cox et al., 2019). In addition, the major active metabolite of THC, 11-OH-THC, and two major inactive metabolites, THC-COOH and THC-COO-Gluc, also exhibited strong inhibition of a number of hepatic CYP enzymes (Nasrin et al., 2020;Nasrin et al., 2021). In the present study, the inhibition potential of major cannabinoids and their metabolites against major hepatic and renal human UGT enzymes were evaluated. ...