One-Week Kava Dietary Supplementation Increases Both Urinary N- and O-Glucuronides of NNAL, a Lung Carcinogen Major Metabolite, among Smokers.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Chemical Research in Toxicology Pub Date : 2024-09-16 Epub Date: 2024-07-13 DOI:10.1021/acs.chemrestox.4c00109
Qi Hu, Zhixin Tang, Allison Lynch, Breanne Freeman, Naomi Fujioka, Ramzi G Salloum, John Malaty, Frank A Orlando, Taimour Langaee, Zhiguang Huo, Chengguo Xing
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Abstract

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 N-glucuronidated NNAL (NNAL-N-gluc), O-glucuronidated NNAL (NNAL-O-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 UGT2B10 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.

Abstract Image

一周卡瓦膳食补充剂会增加吸烟者尿液中NNAL(一种肺致癌物的主要代谢物)的N-和O-葡萄糖醛酸。
4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮(俗称 NNK)是烟草制品中最普遍和最有效的肺致癌物质之一,会增加人类患肺癌的风险。卡瓦通过增加尿液中 4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁醇(NNAL,NNK 的主要代谢产物)的排泄量,从而减少 NNK 诱导的 DNA 损伤,从而有可能降低 NNK 和烟草烟雾诱发肺癌的风险。在这项研究中,我们对服用卡瓦膳食补充剂一周前后收集的尿液样本中的 N-葡萄糖醛酸化 NNAL(NNAL-N-gluc)、O-葡萄糖醛酸化 NNAL(NNAL-O-gluc)和游离 NNAL 进行了定量分析。结果表明,卡瓦能增加 NNAL-N-葡萄糖醛酸化和 O-葡萄糖醛酸化。由于 NNAL-N-葡萄糖醛酸化主要由 UGT2B10 催化,因此对临床试验参与者中具有代表性的单核苷酸多态性(SNPs)进行了分析。具有所分析的四个 SNPs 中的任何一个的人,其 NNAL-N-Glucuronidation 的基础能力似乎会降低。在这些人中,卡瓦也导致了 NNAL-N-葡萄糖醛酸化的较小程度的增加,这表明具有这些 UGT2B10 SNPs 的参与者可能不会从卡瓦增强 NNAL-N 葡萄糖醛酸化中获益太多。总之,我们的研究结果进一步证明,卡瓦能通过增加 N-葡萄糖醛酸和 O-葡萄糖醛酸来提高 NNAL 尿液的解毒能力。UGT2B10 遗传状态不仅有可能预测参与者在 NNAL-N-葡萄糖醛酸化中的基础能力,还有可能预测卡瓦益处的程度。
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来源期刊
CiteScore
7.90
自引率
7.30%
发文量
215
审稿时长
3.5 months
期刊介绍: Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.
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