近日，華南師范大學(xué)環(huán)境學(xué)院應(yīng)光國(guó)教授、趙建亮研究員團(tuán)隊(duì)2021級(jí)碩士研究生張?jiān)丛吹热嗽凇禘nvironment Pollution》上發(fā)表了題為“In vitro metabolism of the emerging contaminant 6PPD-quinone in human and rat liver microsomes: Kinetics, pathways, and mechanism”的論文（DOI: 10.1016/j.envpol.2024.123514，IF=8.9）。該研究使用IPHASE肝微粒體產(chǎn)品以體外代謝反應(yīng)體系探究了輪胎添加劑的抗氧化劑6PPD及其轉(zhuǎn)化產(chǎn)物6PPD醌（6PPD-Q）的I相代謝情況，通過(guò)疑似篩查和非靶向的分析方法闡明了可能的轉(zhuǎn)化產(chǎn)物及轉(zhuǎn)化路徑，結(jié)合表型分析實(shí)驗(yàn)與分子對(duì)接明確了代謝6PPD-Q的關(guān)鍵作用酶。

發(fā)表于《Science》上論文之前報(bào)道了6PPD-Q對(duì)銀鮭魚(yú)的急性致死效應(yīng)，引起了世界范圍的廣泛關(guān)注，輪胎添加劑的安全性備受質(zhì)疑。6PPD-Q是橡膠抗氧化劑6PPD經(jīng)臭氧氧化的轉(zhuǎn)化產(chǎn)物，廣泛存在于各種環(huán)境介質(zhì)中，可通過(guò)吸入、食入和皮膚接觸等多種途徑進(jìn)入人體，進(jìn)而進(jìn)一步進(jìn)入人體的代謝系統(tǒng)。本研究以肝微粒體體外孵育體系探究6PPD和6PPD-Q的生物轉(zhuǎn)化情況，探討6PPD-Q對(duì)人體健康可能的影響。

此項(xiàng)研究結(jié)果表明研究6PPD-Q 在較低濃度下代謝顯著，但在高濃度下代謝程度降低。關(guān)鍵I 相代謝產(chǎn)物為單加氧和進(jìn)一步氧化的產(chǎn)物。與6PPD相比，6PPD-Q所需的代謝時(shí)間相對(duì)較長(zhǎng)，代謝40 μg/L 6PPD的半衰期（t1/2）為28.9 min，而代謝16 μg/L 6PPD-Q的 t1/2則需要29.6 min，代謝80 μg/L 6PPD-Q的 t1/2則要達(dá)到254 min。這也說(shuō)明與輪胎添加劑母體相比，轉(zhuǎn)化產(chǎn)物更難被人體所代謝，可能帶來(lái)更大的環(huán)境健康問(wèn)題。未來(lái)的研究應(yīng)重點(diǎn)關(guān)注輪胎添加劑轉(zhuǎn)化產(chǎn)物，特別是其他PPD-Qs的轉(zhuǎn)化產(chǎn)物，以充分評(píng)估其對(duì)人類健康的影響。

摘    要

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) is an ozonation product of the rubber antioxidant N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD). 6PPD-Q has recently been detected in various environmental media, which may enter the human body via inhalation and skin contact pathways. However, the human metabolism of 6PPD-Q has remained unknown. This study investigated the in vitro Cytochrome P450-mediated metabolism of 6PPD-Q in human and rat liver microsomes (HLMs and RLMs). 6PPD-Q was significantly metabolized at lower concentrations but slowed at high concentrations. The intrinsic clearance (CLint) of 6PPD-Q was 21.10 and 18.58 μL min− 1 mg− 1 protein of HLMs and RLMs, respectively, suggesting low metabolic ability compared with other reported pollutants. Seven metabolites and one intermediate were identified, and metabolites were predicted immunotoxic or mutagenic toxicity. Mono- and di-oxygenation reactions were the main phase I in vitro metabolic pathways. Enzyme inhibition experiments and molecular docking techniques were further used to reveal the metabolic mechanism. CYP1A2, 3A4, and 2C19, especially 

CYP1A2, play critical roles in 6PPD-Q metabolism in HLMs, whereas 6PPD-Q is extensively metabolized in RLMs. Our study is the first to demonstrate the in vitro metabolic profile of 6PPD-Q in HLMs and RLMs. The results will significantly contribute to future human health management targeting the emerging pollutant 6PPD-Q.

完整版文獻(xiàn)可在【IPHASE】公眾號(hào)后臺(tái)留言【獲取文章】

再次恭喜文獻(xiàn)發(fā)表，以及對(duì)我司產(chǎn)品的認(rèn)可，希望以上文獻(xiàn)能幫助大家了解目前研究進(jìn)展及我們的核心技術(shù)，歡迎各位新老客戶聯(lián)系我們咨詢、提出意見(jiàn)，愿我們的努力成果與您的科研碰撞出不一樣的火花！

發(fā)    文    章    得    獎(jiǎng)    勵(lì)

凡使用本公司產(chǎn)品，在國(guó)內(nèi)及國(guó)際刊物上發(fā)表論文（論文發(fā)表日起一年內(nèi)），并注明產(chǎn)品屬于IPHASE BIOSCIENCES/匯智和源生物技術(shù)（蘇州）有限公司所有，即可申請(qǐng)獎(jiǎng)勵(lì)。根據(jù)發(fā)表刊物影響因子不同，給予不同金額獎(jiǎng)品：

非SCI論文及IF≤5分，500元禮品；

5分＜IF≤8分 800元；

8分＜IF≤10分 1000元；

IF≥10分 2000元；

注：禮品卡也可兌換同等金額產(chǎn)品購(gòu)買抵用券；

活動(dòng)多多，禮品豐厚，快來(lái)參與吧！

關(guān)    于    我    們

匯智和源，致力于為創(chuàng)新藥研發(fā)企業(yè)及生命科學(xué)研究機(jī)構(gòu)提供高品質(zhì)的生物試劑，IPHASE為公司核心品牌，品牌宗旨“Innovative Reagents For Innovative Research”。