{"title":"Minocycline Regulates PARP-1 and HDAC3 Pathways to Inhibit Inflammation and Oxidative Stress in LPS-Induced Acute Lung Injury.","authors":"Chao Luo, Xixi Zhu, Jiefei Liang, Chunyan Zhu, Guohua Shen, Weibin Wu","doi":"10.5812/ijpr-161381","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells, resulting in acute hypoxemic respiratory failure. Minocycline, a tetracycline antibiotic, is known to have excellent anti-inflammatory activity.</p><p><strong>Objectives: </strong>The present study aims to reveal the protective effect and potential mechanism of the anti-inflammatory effects of minocycline on lipopolysaccharide (LPS)-induced ALI in mice and A549 cells.</p><p><strong>Methods: </strong>We investigated the role of minocycline in ALI mice and inflammation-induced damage to alveolar epithelial cells using various experimental approaches, including histological staining, enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR, flow cytometry, western blot analysis, and other relevant assays.</p><p><strong>Results: </strong>Pre-treatment with minocycline effectively attenuated LPS-induced ALI in vivo by inhibiting inflammation and oxidative damage, improving pathological changes in the lungs, alleviating pulmonary edema and protein exudation, and suppressing neutrophil aggregation. In vitro, minocycline suppressed the inflammatory response of human alveolar epithelial A549 cells, as evidenced by the inhibition of inflammatory cytokine and oxidative damage biomarker expression, reduction in intracellular reactive oxygen species (ROS) production, alleviation of mitochondrial damage, and inhibition of cell apoptosis. Subsequent mechanistic studies revealed that the protective effects of minocycline against ALI may be attributed to its suppression of poly (ADP-ribose) polymerase-1 (PARP-1) and histone deacetylase 3 (HDAC3) expression.</p><p><strong>Conclusions: </strong>In conclusion, our study presents minocycline as a potential candidate for ALI therapy and provides an experimental foundation for investigating its anti-inflammatory mechanisms in the treatment of ALI. Further therapeutic value awaits verification in clinical and preclinical studies.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e161381"},"PeriodicalIF":1.8000,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297026/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Pharmaceutical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5812/ijpr-161381","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells, resulting in acute hypoxemic respiratory failure. Minocycline, a tetracycline antibiotic, is known to have excellent anti-inflammatory activity.
Objectives: The present study aims to reveal the protective effect and potential mechanism of the anti-inflammatory effects of minocycline on lipopolysaccharide (LPS)-induced ALI in mice and A549 cells.
Methods: We investigated the role of minocycline in ALI mice and inflammation-induced damage to alveolar epithelial cells using various experimental approaches, including histological staining, enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR, flow cytometry, western blot analysis, and other relevant assays.
Results: Pre-treatment with minocycline effectively attenuated LPS-induced ALI in vivo by inhibiting inflammation and oxidative damage, improving pathological changes in the lungs, alleviating pulmonary edema and protein exudation, and suppressing neutrophil aggregation. In vitro, minocycline suppressed the inflammatory response of human alveolar epithelial A549 cells, as evidenced by the inhibition of inflammatory cytokine and oxidative damage biomarker expression, reduction in intracellular reactive oxygen species (ROS) production, alleviation of mitochondrial damage, and inhibition of cell apoptosis. Subsequent mechanistic studies revealed that the protective effects of minocycline against ALI may be attributed to its suppression of poly (ADP-ribose) polymerase-1 (PARP-1) and histone deacetylase 3 (HDAC3) expression.
Conclusions: In conclusion, our study presents minocycline as a potential candidate for ALI therapy and provides an experimental foundation for investigating its anti-inflammatory mechanisms in the treatment of ALI. Further therapeutic value awaits verification in clinical and preclinical studies.
期刊介绍：
The Iranian Journal of Pharmaceutical Research (IJPR) is a peer-reviewed multi-disciplinary pharmaceutical publication, scheduled to appear quarterly and serve as a means for scientific information exchange in the international pharmaceutical forum. Specific scientific topics of interest to the journal include, but are not limited to: pharmaceutics, industrial pharmacy, pharmacognosy, toxicology, medicinal chemistry, novel analytical methods for drug characterization, computational and modeling approaches to drug design, bio-medical experience, clinical investigation, rational drug prescribing, pharmacoeconomics, biotechnology, nanotechnology, biopharmaceutics and physical pharmacy.
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