{"title":"Protective effect of modafinil in bisphenol A-induced lung injury in rats: roles of SIRT1-dependent signaling pathways.","authors":"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","doi":"10.1080/08923973.2025.2469218","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>MOD possesses potent ameliorative effects against lung injury caused by BPA <i>via</i> reducing oxidative stress, inflammatory process, and apoptosis through regulation of SIRT1/Nrf2 and SIRT1/FOXO1 signaling pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"252-262"},"PeriodicalIF":2.9000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunopharmacology and Immunotoxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08923973.2025.2469218","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/3 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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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