莫达非尼对双酚a诱导大鼠肺损伤的保护作用:sirt1依赖性信号通路的作用

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Walaa Yehia Abdelzaher, Marwa Hassan, Nashwa Fathy Gamal El-Tahawy, Abdel Hamid Sayed AboBakr Ali, DoaaMohamed Elroby Ali, Meriam N N Rezk, Zainab Hassan Saeed, Ayman Geddawy
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引用次数: 0

摘要

背景:双酚A (BPA)是一种用于制造环氧树脂、聚碳酸酯塑料的工业化学品。我们的目的是评估莫达非尼(modafinil, MOD)对bpa诱导的肺损伤可能的保护作用。材料与方法:将24只成年雄性白化Wistar大鼠分为4组:对照组,MOD组:给予莫达非尼10 mg/kg/d,连续4周,BPA组:给予双酚A (500 mg/kg/d),连续4周,MOD/BPA组:给予MOD+ BPA。我们测量了动脉血气(ABG)、丙二醛(MDA)、一氧化氮(NOx)、总抗氧化能力(TAC)、白介素-1b (IL-1b)、Sirtuin 1型(SIRT1)、Keap1、核因子(红细胞衍生2)样2 (Nrf2)、caspase-3和forkhead-box转录因子1 (FOXO1)水平、肿瘤坏死因子α (TNF-α)、核因子κB (NF-κB)、凋亡的bcl -2相关蛋白x (Bax)和抗凋亡的b细胞白血病/淋巴瘤2蛋白(Bcl2)和血红素加氧酶-1 (HO-1)基因的表达。此外;观察组织学变化、白细胞介素-6 (IL-6)免疫表达。结果:BPA组小鼠二氧化碳分压(PaCO2)、MDA、NOx、IL-1b、keap1、FOXO1、caspase-3水平显著升高;TNF-α和NF-Κb、Bax和HO-1基因表达、IL-6在肺泡壁细胞、间质细胞和浸润性炎症细胞中的免疫表达显著升高。此外;肺损伤呈明显的毒性组织学改变。同时,PaO2分压、TAC、SIRT1、Nrf2水平及Bcl2基因表达均明显降低。MOD在所有参数上都有显著的改善。结论:MOD通过调节SIRT1/Nrf2和SIRT1/FOXO1信号通路,减少氧化应激、炎症过程和细胞凋亡,对BPA所致肺损伤具有明显的改善作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protective effect of modafinil in bisphenol A-induced lung injury in rats: roles of SIRT1-dependent signaling pathways.

Background: Bisphenol A (BPA) is an industrial chemical used in manufacturing epoxy resins, polycarbonate plastics. We aimed to evaluate the possible protective effect of modafinil (MOD) in BPA-induced lung injury.

Materials and methods: Twenty-four adult male albino Wistar rats were divided into four groups: Control group, MOD group: rats received modafinil 10 mg/kg/day for 4 weeks, BPA group: rats received Bisphenol A (500 mg/kg/day) for 4 weeks, MOD/BPA group: rats received MOD+ BPA. We measured arterial blood gas (ABG), malondialdehyde (MDA), nitric oxide (NOx), total antioxidant capacity (TAC), interlukin-1b (IL-1b), Sirtuin type 1 (SIRT1), Keap1, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), caspase-3 and forkhead-box transcription factor1 (FOXO1) levels, tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), apoptotic Bcl-2-associated protein x (Bax) and anti-apoptotic B-cell leukemia/lymphoma 2 protein (Bcl2) and Heme Oxygenase-1 (HO-1) gene expression. Furthermore; histological changes, interlukin-6 (IL-6) immuno-expression were evaluated.

Results: BPA group showed significant increase in the partial pressure of carbon dioxide (PaCO2), MDA, NOx, IL-1b, keap1 and FOXO1, caspase-3 levels; TNF-α and NF-Κb, Bax and HO-1 gene expression, IL-6 exhibited a notable rise in immune-expression in the alveolar wall cells, interstitial cells, and infiltrating inflammatory cells. Moreover; it showed toxic histological changes of marked lung injury. Meanwhile, there is a significant decrease in the partial pressure of oxygen (PaO2), TAC, SIRT1, Nrf2 levels, and Bcl2 gene expression. MOD showed a significant improvement in all parameters.

Conclusion: MOD possesses potent ameliorative effects against lung injury caused by BPA via reducing oxidative stress, inflammatory process, and apoptosis through regulation of SIRT1/Nrf2 and SIRT1/FOXO1 signaling pathways.

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来源期刊
CiteScore
5.40
自引率
0.00%
发文量
133
审稿时长
4-8 weeks
期刊介绍: The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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