Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Sci Rep. 2021 Aug 30;11(1):17393. doi: 10.1038/s41598-021-96807-5.
In this study, we investigated whether intravenously self-administered nicotine with menthol and audiovisual cue modulates nicotine-metabolizing CYP2A6, oxidative stress modulators, and cytokines/chemokines in plasma extracellular vesicles (EVs) in rats. We assigned rats to self-administered nicotine with: (a) audiovisual cue (AV), (b) menthol, and (c) menthol and AV cue. We found increased levels of CD9 in plasma EVs after self-administered nicotine with menthol and AV cue. Moreover, expression of CYP2A6 in plasma EVs was significantly increased after self-administered nicotine in response to menthol and AV cue. However, despite an upward trend on SOD1 and catalase, increase was not found to be statistically significant, while total antioxidant capacity was found to be significantly increased in plasma and plasma EVs obtained after self-administered nicotine with menthol and AV cue. Among cytokine and chemokine profiling, we found a significant increase in the levels of MCP-1 after self-administered nicotine with menthol and AV cue and complete packaging of IL-1β in EVs. Taken together, the study provides evidence that nicotine in response to menthol and AV cues can package altered levels of CYP2A6, and cytokines/chemokines in plasma EVs that may contribute to cell-cell communication, nicotine metabolism, and inflammation upon cigarette smoking.
在这项研究中,我们研究了静脉内自我给予含薄荷醇和视听线索的尼古丁是否调节大鼠血浆细胞外囊泡(EV)中的尼古丁代谢 CYP2A6、氧化应激调节剂和细胞因子/趋化因子。我们将大鼠分为三组,分别接受以下处理:(a)视听线索(AV),(b)薄荷醇,和(c)薄荷醇和 AV 线索。我们发现,在静脉内自我给予含薄荷醇和视听线索的尼古丁后,血浆 EV 中的 CD9 水平升高。此外,在自我给予尼古丁后,血浆 EV 中的 CYP2A6 表达显著增加,这是对薄荷醇和视听线索的反应。然而,尽管 SOD1 和过氧化氢酶呈上升趋势,但增加并不显著,而在自我给予含薄荷醇和视听线索的尼古丁后,血浆和血浆 EV 中的总抗氧化能力显著增加。在细胞因子和趋化因子分析中,我们发现,在自我给予含薄荷醇和视听线索的尼古丁后,MCP-1 水平显著增加,而 EV 中完全包裹了 IL-1β。综上所述,该研究提供了证据表明,薄荷醇和视听线索会导致尼古丁包装改变的 CYP2A6 水平,以及细胞因子/趋化因子在血浆 EV 中的水平变化,这可能有助于细胞间通讯、尼古丁代谢和吸烟引起的炎症。