Chemical Research in Toxicology最新文献

{"title":"Photosensitized Oxidation of Free and Peptide Tryptophan to <i>N</i>-Formylkynurenine.","authors":"Jesuán J Farías, M Laura Dántola, Andrés H Thomas","doi":"10.1021/acs.chemrestox.4c00229","DOIUrl":"10.1021/acs.chemrestox.4c00229","url":null,"abstract":"<p><p>The oxidation of proteins and, in particular, of tryptophan (Trp) residues leads to chemical modifications that can affect the structure and function. The oxidative damage to proteins in photochemical processes is relevant in the skin and eyes and is related to a series of pathologies triggered by exposure to electromagnetic radiation. In this work, we studied the photosensitized formation of <i>N</i>-formylkynurenine (NFKyn) from Trp in different reaction systems. We used two substrates: free Trp and a peptide of nine amino acid residues, with Trp being the only oxidizable residue. Two different photosensitizers were employed: Rose Bengal (RB) and pterin (Ptr). The former is a typical type II photosensitizer [acts by producing singlet oxygen (¹O₂)]. Ptr is the parent compound of oxidized or aromatic pterins, natural photosensitizers that accumulate in human skin under certain pathological conditions and act mainly through type I mechanisms (generation of radicals). Experimental data were collected in steady photolysis, and the irradiated solutions were analyzed by chromatography (HPLC). Results indicate that the reaction of Trp with ¹O₂ initiates the process leading to NFKyn, but different competitive pathways take place depending on the photosensitizer and the substrate. In Ptr-photosensitization, a type I mechanism is involved in secondary reactions accelerating the formation of NFKyn when free Trp is the substrate.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward an Explainable Large Language Model for the Automatic Identification of the Drug-Induced Liver Injury Literature.","authors":"Chunwei Ma, Russell D Wolfinger","doi":"10.1021/acs.chemrestox.4c00134","DOIUrl":"10.1021/acs.chemrestox.4c00134","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) stands as a significant concern in drug safety, representing the primary cause of acute liver failure. Identifying the scientific literature related to DILI is crucial for monitoring, investigating, and conducting meta-analyses of drug safety issues. Given the intricate and often obscure nature of drug interactions, simple keyword searching can be insufficient for the exhaustive retrieval of the DILI-relevant literature. Manual curation of DILI-related publications demands pharmaceutical expertise and is susceptible to errors, severely limiting throughput. Despite numerous efforts utilizing cutting-edge natural language processing and deep learning techniques to automatically identify the DILI-related literature, their performance remains suboptimal for real-world applications in clinical research and regulatory contexts. In the past year, large language models (LLMs) such as ChatGPT and its open-source counterpart LLaMA have achieved groundbreaking progress in natural language understanding and question answering, paving the way for the automated, high-throughput identification of the DILI-related literature and subsequent analysis. Leveraging a large-scale public dataset comprising 14 203 training publications from the CAMDA 2022 literature AI challenge, we have developed what we believe to be the first LLM specialized in DILI analysis based on LLaMA-2. In comparison with other smaller language models such as BERT, GPT, and their variants, LLaMA-2 exhibits an enhanced out-of-fold accuracy of 97.19% and area under the ROC curve of 0.9947 using 3-fold cross-validation on the training set. Despite LLMs' initial design for dialogue systems, our study illustrates their successful adaptation into accurate classifiers for automated identification of the DILI-related literature from vast collections of documents. This work is a step toward unleashing the potential of LLMs in the context of regulatory science and facilitating the regulatory review process.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Dual PPAR δ/γ Partial Agonist Induces Hepatic Lipid Accumulation through Direct Binding and Inhibition of AKT1 Phosphorylation, Mediating CD36 Upregulation.","authors":"Xiaotong Cai, Qin Zhang, Jiwei Wang, Yingying Miao, Yuqing Sun, Ziyin Xia, Luyong Zhang, Qinwei Yu, Zhenzhou Jiang","doi":"10.1021/acs.chemrestox.4c00268","DOIUrl":"10.1021/acs.chemrestox.4c00268","url":null,"abstract":"<p><p>ZLY06 is a dual agonist of peroxisome proliferator-activated receptor (PPAR) δ/γ, showing potential therapeutic effects on metabolic syndrome. However, our research has revealed that ZLY06 exhibits hepatotoxicity in normal C57BL/6J mice, though the precise mechanism remains unclear. This study aims to investigate the manifestations and mechanisms of ZLY06-induced hepatotoxicity. We administered ZLY06 via oral gavage to C57BL/6J mice (once daily for six weeks) and monitored various indicators to preliminarily explore its hepatotoxicity. Additionally, we further investigate the specific mechanisms of ZLY06-induced hepatotoxicity using PPAR inhibitors (GW9662 and GSK0660) and the Protein kinase B (AKT) activator (SC79). Results showed that ZLY06 led to increased serum ALP, ALT and AST, as well as elevated liver index and hepatic lipid levels. There was upregulation in the gene and protein expression of lipid metabolism-related molecules <i>Acc</i>, <i>Scd1</i>, <i>Cd36</i>, <i>Fabp1</i> and <i>Fabp2</i> in hepatocytes, with <i>Cd36</i> showing the most significant change. Furthermore, cotreatment with SC79 significantly reduced ZLY06-induced hepatotoxicity in AML12 cells, evidenced by decreased intracellular TG levels and downregulation of CD36 expression. Specific knockdown of CD36 also mitigated ZLY06-induced hepatotoxicity. The study found that ZLY06 may bind to AKT1, inhibiting its phosphorylation activation, with the downregulation of p-AKT1 preceding the upregulation of CD36. In summary, ZLY06 mediates the upregulation of CD36 by potentially binding to and inhibiting the phosphorylation of AKT1, leading to hepatic lipid metabolism disorder and inducing liver toxicity.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Glioblastoma: Efficacy of Ruthenium-Based Drugs.","authors":"Puthiyavalappil Rasin, Sravan Sangeeth Surendran, Karthik K S, Jebiti Haribabu, Anandaram Sreekanth","doi":"10.1021/acs.chemrestox.4c00188","DOIUrl":"10.1021/acs.chemrestox.4c00188","url":null,"abstract":"<p><p>Ruthenium compounds offer improved selectivity and fewer side effects compared to platinum-based drugs in glioblastoma treatment. Insights into their interactions with transferrin suggest targeted drug delivery, while photoactivated chemotherapy is a novel cytotoxic approach in tumor tissues.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Cytochrome P450 Substrates Using the Explainable Multitask Deep Learning Models.","authors":"Jiaojiao Fang, Yan Tang, Changda Gong, Zejun Huang, Yanjun Feng, Guixia Liu, Yun Tang, Weihua Li","doi":"10.1021/acs.chemrestox.4c00199","DOIUrl":"10.1021/acs.chemrestox.4c00199","url":null,"abstract":"<p><p>Cytochromes P450 (P450s or CYPs) are the most important phase I metabolic enzymes in the human body and are responsible for metabolizing ∼75% of the clinically used drugs. P450-mediated metabolism is also closely associated with the formation of toxic metabolites and drug-drug interactions. Therefore, it is of high importance to predict if a compound is the substrate of a given P450 in the early stage of drug development. In this study, we built the multitask learning models to simultaneously predict the substrates of five major drug-metabolizing P450 enzymes, namely, CYP3A4, 2C9, 2C19, 2D6, and 1A2, based on the collected substrate data sets. Compared to the single-task model and conventional machine learning models, the multitask fingerprints and graph neural networks model achieved superior performance with the average AUC values of 90.8% on the test set. Notably, the multitask model demonstrated its good performance on the small amount of substrate data sets such as CYP1A2, 2C9, and 2C19. In addition, the Shapley additive explanation and the attention mechanism were used to reveal specific substructures associated with P450 substrates, which were further confirmed and complemented by the substructure mining tool and the literature.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triphenyl Phosphate Alters Methyltransferase Expression and Induces Genome-Wide Aberrant DNA Methylation in Zebrafish Larvae.","authors":"Chander K Negi, Lucie Bláhová, Audrey Phan, Lola Bajard, Ludek Blaha","doi":"10.1021/acs.chemrestox.4c00223","DOIUrl":"10.1021/acs.chemrestox.4c00223","url":null,"abstract":"<p><p>Emerging environmental contaminants, organophosphate flame retardants (OPFRs), pose significant threats to ecosystems and human health. Despite numerous studies reporting the toxic effects of OPFRs, research on their epigenetic alterations remains limited. In this study, we investigated the effects of exposure to 2-ethylhexyl diphenyl phosphate (EHDPP), tricresyl phosphate (TMPP), and triphenyl phosphate (TPHP) on DNA methylation patterns during zebrafish embryonic development. We assessed general toxicity and morphological changes, measured global DNA methylation and hydroxymethylation levels, and evaluated DNA methyltransferase (DNMT) enzyme activity, as well as mRNA expression of DNMTs and ten-eleven translocation (TET) methylcytosine dioxygenase genes. Additionally, we analyzed genome-wide methylation patterns in zebrafish larvae using reduced-representation bisulfite sequencing. Our morphological assessment revealed no general toxicity, but a statistically significant yet subtle decrease in body length following exposure to TMPP and EHDPP, along with a reduction in head height after TPHP exposure, was observed. Eye diameter and head width were unaffected by any of the OPFRs. There were no significant changes in global DNA methylation levels in any exposure group, and TMPP showed no clear effect on DNMT expression. However, EHDPP significantly decreased only DNMT1 expression, while TPHP exposure reduced the expression of several DNMT orthologues and TETs in zebrafish larvae, leading to genome-wide aberrant DNA methylation. Differential methylation occurred primarily in introns (43%) and intergenic regions (37%), with 9% and 10% occurring in exons and promoter regions, respectively. Pathway enrichment analysis of differentially methylated region-associated genes indicated that TPHP exposure enhanced several biological and molecular functions corresponding to metabolism and neurological development. KEGG enrichment analysis further revealed TPHP-mediated potential effects on several signaling pathways including TGFβ, cytokine, and insulin signaling. This study identifies specific changes in DNA methylation in zebrafish larvae after TPHP exposure and brings novel insights into the epigenetic mode of action of TPHP.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of Thymus Atrophy and Disruption of Thymocyte Development by Fipronil through Dysregulation of IL-7-Associated Genes.","authors":"Jui-Fang Kuo, Hsin-Ying Wu, Chun-Wei Tung, Wei-Hsiang Huang, Chen-Si Lin, Chia-Chi Wang","doi":"10.1021/acs.chemrestox.4c00060","DOIUrl":"10.1021/acs.chemrestox.4c00060","url":null,"abstract":"<p><p>The susceptibility of the immune system to immunotoxic chemicals is evident, particularly in the thymus, a vital primary immune organ prone to atrophy due to exposure to toxicants. Fipronil (FPN), a widely used insecticide, is of concern due to its potential neurotoxicity, hepatotoxicity, and immunotoxicity. Our previous study showed that FPN disturbed the antigen-specific T-cell functionality <i>in vivo</i>. As T-cell lineage commitment and thymopoiesis are closely interconnected with the normal function of the T-cell-mediated immune responses, this study aims to further examine the toxic effects of FPN on thymocyte development. In this study, 4-week-old BALB/c mice received seven doses of FPN (1, 5, 10 mg/kg) by gavage. Thymus size, medulla/cortex ratio, total thymocyte counts, double-positive thymocyte population, and IL-7-positive cells decreased dose-dependently. IL-7 aids the differentiation of early T-cell precursors into mature T cells, and several essential genes contribute to the maturation of T cells in the thymus. <i>Foxn</i>1 ensures that the thymic microenvironment is suitable for the maturation of T-cell precursors. <i>Lyl</i>1 is involved in specifying lymphoid cells and maintaining T-cell development in the thymus. The <i>c-Kit/SCF</i> collaboration fosters a supportive thymic milieu to promote the formation of functional T cells. The expression of <i>IL-</i>7, <i>IL-</i>7<i>R</i>, <i>c-Kit</i>, <i>SCF</i>, <i>Foxn</i>1, and <i>Lyl</i>1 genes in the thymus was significantly diminished in FPN-treated groups with the concordance with the reduction of IL-7 signaling proteins (IL-7, IL-7R, c-KIT, SCF, LYL1, FOXO3A, and GABPA), suggesting that the dysregulation of T-cell lineage-related genes may contribute to the thymic atrophy induced by FPN. In addition, FPN disturbed the functionality of thymocytes with an increase of IL-4 and IFN-γ production and a decrease of IL-2 secretion after T-cell mitogen stimulation <i>ex vivo</i>. Collectively, FPN significantly deregulated genes related to T-cell progenitor differentiation, survival, and expansion, potentially leading to impaired thymopoiesis.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical Methodologies to Detect N-Nitrosamine Impurities in Active Pharmaceutical Ingredients, Drug Products and Other Matrices.","authors":"Krishna Moorthy Manchuri, Mahammad Ali Shaik, Venkata Subba Reddy Gopireddy, Naziya Sultana, Sreenivasarao Gogineni","doi":"10.1021/acs.chemrestox.4c00234","DOIUrl":"10.1021/acs.chemrestox.4c00234","url":null,"abstract":"<p><p>Since 2018, N-nitrosamine impurities have become a widespread concern in the global regulatory landscape of pharmaceutical products. This concern arises due to their potential for contamination, toxicity, carcinogenicity, and mutagenicity and their presence in many active pharmaceutical ingredients, drug products, and other matrices. N-Nitrosamine impurities in humans can lead to severe chemical toxicity effects. These include carcinogenic effects, metabolic disruptions, reproductive harm, liver diseases, obesity, DNA damage, cell death, chromosomal alterations, birth defects, and pregnancy loss. They are particularly known to cause cancer (tumors) in various organs and tissues such as the liver, lungs, nasal cavity, esophagus, pancreas, stomach, urinary bladder, colon, kidneys, and central nervous system. Additionally, N-nitrosamine impurities may contribute to the development of Alzheimer's and Parkinson's diseases and type-2 diabetes. Therefore, it is very important to control or avoid them by enhancing effective analytical methodologies using cutting-edge analytical techniques such as LC-MS, GC-MS, CE-MS, SFC, etc. Moreover, these analytical methods need to be sensitive and selective with suitable precision and accuracy, so that the actual amounts of N-nitrosamine impurities can be detected and quantified appropriately in drugs. Regulatory agencies such as the US FDA, EMA, ICH, WHO, etc. need to focus more on the hazards of N-nitrosamine impurities by providing guidance and regular updates to drug manufacturers and applicants. Similarly, drug manufacturers should be more vigilant to avoid nitrosating agents and secondary amines during the manufacturing processes. Numerous review articles have been published recently by various researchers, focusing on N-nitrosamine impurities found in previously notified products, including sartans, metformin, and ranitidine. These impurities have also been detected in a wide range of other products. Consequently, this review aims to concentrate on products recently reported to contain N-nitrosamine impurities. These products include rifampicin, champix, famotidine, nizatidine, atorvastatin, bumetanide, itraconazole, diovan, enalapril, propranolol, lisinopril, duloxetine, rivaroxaban, pioglitazones, glifizones, cilostazol, and sunitinib.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omeprazole-Associated Atypical Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in a Patient with Positive In Vitro Diagnostic Testing to Multiple Proton Pump Inhibitors.","authors":"Sophie Grice, Sean Hammond, Lucy Hampson, Annette Wagner, Dean J Naisbitt","doi":"10.1021/acs.chemrestox.4c00225","DOIUrl":"10.1021/acs.chemrestox.4c00225","url":null,"abstract":"<p><p>Proton pump inhibitors (PPIs) are a commonly used class of drugs with a good safety profile. However, their use is associated with rare cases of severe skin reaction. Herein, we present details of a patient who developed two episodes of omeprazole-induced delayed-onset hypersensitivity (atypical drug reaction with eosinophilia and systemic symptoms [DRESS]). Lymphocytes from the patient were stimulated to proliferate and secrete cytokines and cytolytic molecules when treated with the drug. T-cell cross-reactivity was observed with structurally related PPIs. Hence, other PPIs have the potential to cause further serious immune-related adverse events in patients who present with hypersensitivity to a primary PPI.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-Week Kava Dietary Supplementation Increases Both Urinary <i>N</i>- and <i>O</i>-Glucuronides of NNAL, a Lung Carcinogen Major Metabolite, among Smokers.","authors":"Qi Hu, Zhixin Tang, Allison Lynch, Breanne Freeman, Naomi Fujioka, Ramzi G Salloum, John Malaty, Frank A Orlando, Taimour Langaee, Zhiguang Huo, Chengguo Xing","doi":"10.1021/acs.chemrestox.4c00109","DOIUrl":"10.1021/acs.chemrestox.4c00109","url":null,"abstract":"<p><p>4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (commonly known as NNK) is one of the most prevalent and potent pulmonary carcinogens in tobacco products that increases the human lung cancer risk. Kava has the potential to reduce NNK and tobacco smoke-induced lung cancer risk by enhancing urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK) and thus reducing NNK-induced DNA damage. In this study, we quantified <i>N</i>-glucuronidated NNAL (NNAL-<i>N</i>-gluc), <i>O</i>-glucuronidated NNAL (NNAL-<i>O</i>-gluc), and free NNAL in the urine samples collected before and after 1-week kava dietary supplementation. The results showed that kava increased both NNAL-N-glucuronidation and O-glucuronidation. Since NNAL-N-glucuronidation is dominantly catalyzed by UGT2B10, its representative single-nucleotide polymorphisms (SNPs) were analyzed among the clinical trial participants. Individuals with any of the four analyzed SNPs appear to have a reduced basal capacity in NNAL-N-glucuronidation. Among these individuals, kava also resulted in a smaller extent of increases in NNAL-N-glucuronidation, suggesting that participants with those <i>UGT</i>2<i>B</i>10 SNPs may not benefit as much from kava with respect to enhancing NNAL-N-glucuronidation. In summary, our results provide further evidence that kava enhances NNAL urinary detoxification via an increase in both N-glucuronidation and O-glucuronidation. UGT2B10 genetic status has not only the potential to predict the basal capacity of the participants in NNAL-N-glucuronidation but also potentially the extent of kava benefits.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}