食源性致癌物 2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)会扰乱草履虫的昼夜节律,而紫檀芪(PSB)可改善其昼夜节律

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-09-10 DOI:10.1007/s00204-024-03857-5
Chun-Han Chang, Pei-Ling Yen, Min-Hsiung Pan, Vivian Hsiu-Chuan Liao
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引用次数: 0

摘要

食源性 2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)是一种潜在的人类致癌物质,在熟肉中含量丰富。昼夜节律是重要的生物振荡,但 PhIP 对昼夜节律系统的负面影响和缓解潜力仍未得到充分探索。我们研究了 PhIP 对草履虫昼夜节律的影响以及植物化学抗氧化剂紫檀芪(PSB)的缓解作用。我们的研究表明,暴露于 10 μM PhIP 会扰乱秀丽隐杆线虫的 24 小时昼夜节律,而同时暴露于 100 μM PSB 会减轻这种影响。此外,PhIP 诱导的昼夜节律紊乱可能与氧化应激抗性缺陷有关,而氧化应激抗性缺陷与 DAF-16/FOXO 通路有关,并受到 PSB 的调节。分子对接表明,PhIP 和 PSB 与 DAF-16 的结合方式相似。此外,10 μM PhIP 会抑制核心时钟基因 prdx-2 的节律性表达,而 100 μM PSB 则会恢复这种表达。这项研究的结果提供了一个新的视角,揭示了食源性污染物(如 PhIP)可能如何导致昼夜节律紊乱,并提出了 PSB 在高等生物中减轻这些影响的潜力。
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The food-borne carcinogenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) disrupts circadian rhythms and ameliorated by pterostilbene (PSB) in Caenorhabditis elegans

The food-borne 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potential human carcinogen abundant in cooked meat. While circadian rhythms are crucial biological oscillations, the negative impact of PhIP on circadian systems and the potential of mitigation remain underexplored. We investigated the effects of PhIP on circadian rhythms and the mitigating effects of the phytochemical antioxidant pterostilbene (PSB) in Caenorhabditis elegans. We show that exposure to 10 μM PhIP disrupts the 24-h circadian rhythms of C. elegans, an effect mitigated by co-exposure to 100 μM PSB. In addition, PhIP-induced circadian disruption can be linked to defective oxidative stress resistance, which is associated with the DAF-16/FOXO pathway and is modulated by PSB. Molecular docking suggested that PhIP and PSB bind similarly to DAF-16. Moreover, 10 μM PhIP abolished the rhythmic expression of the core clock gene prdx-2, which is restored by 100 μM PSB. Findings from this study provide novel insight of how food-borne contaminant like PhIP may contribute to the disruption of circadian rhythms and suggest potential for PSB to mitigate these effects in higher organisms.

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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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