ArticleBrazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica2018
Saquinavir plus methylprednisolone ameliorates experimental acute lung injury.
Article in Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Dabigatran Prevents Lipopolysaccharide-Mediated Apoptosis in Zebrafish Through a Thrombin-Independent Mechanism.Shock (Augusta, Ga.) · 2026Article
- Aquaporins: a novel perspective in the treatment of lung diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Paritaprevir ameliorates experimental acute lung injury in vitro and in vivo.Archives of pharmacal research · 2023Article
- Symmetrical peripheral gangrene: potential mechanisms and therapeutic approaches in severe COVID-19.Frontiers in cardiovascular medicine · 2023Review
- Tailored modulation of S100A1 and RASSF8 expression by butanediamide augments healing of rotator cuff tears.PeerJ · 2023Article
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- The protective role of raltegravir in experimental acute lung injury in vitro and in vivo.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2022Article
- Study on the Efficacy and Safety of Ambroxol Combined with Methylprednisolone in Patients with Acute Lung Injury.BioMed research international · 2021Article
- The Impact of Matrix Metalloproteinase-9 on the Sequential Steps of the Metastatic Process.International journal of molecular sciences · 2020Review
- The Anti-Angiogenic Effects of Anti-Human Immunodeficiency Virus Drugs.Frontiers in oncology · 2020Review
- Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment.Mediators of inflammation · 2020Review
- Differential Regulation of LPS-Mediated VE-Cadherin Disruption in Human Endothelial Cells and the Underlying Signaling Pathways: A Mini Review.Frontiers in cell and developmental biology · 2019Review
- Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications.Respiratory medicineReview
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoid insensitivity is an important barrier to the treatment of several inflammatory diseases, including acute lung injury (ALI). Saquinavir (SQV) is an inhibitor of the human immunodeficiency virus protease, and the therapeutic effects of SQV in ALI accompanied with glucocorticoid insensitivity have not been previously investigated. In this study, the effects of SQV on lipopolysaccharide (LPS)-mediated injury in human pulmonary microvascular endothelial cells (HPMECs), human type I alveolar epithelial cells (AT I), and alveolar macrophages were determined. In addition, the effects of SQV on an LPS-induced ALI model with or without methylprednisolone (MPS) were studied. In LPS-stimulated HPMECs, SQV treatment resulted in a decrease of high mobility group box 1 (HMGB1), phospho-NF-κB (p-NF-κB), and toll-like receptor 4 (TLR4), and an increase of VE-cadherin. Compared to MPS alone, MPS plus SQV attenuated the decrease of glucocorticoid receptor alpha (GRα) and IκBα in LPS-stimulated HPMECs. HMGB1, TLR4, and p-NF-κB expression were also lessened in LPS-stimulated alveolar macrophages with SQV treatment. In addition, SQV reduced the injury in human AT I with a decrease of HMGB1 and p-NF-κB, and with an increase of aquaporin 5 (AQP 5). SQV ameliorated the lung injury caused by LPS in rats with reductions in vascular permeability, myeloperoxidase activity (MPO) and histopathological scores, and with lowered HMGB1, TLR4, and p-NF-κB expression, but with enhanced VE-cadherin expression. By comparison, SQV plus MPS increased GRα and IκBα in lung tissues of rats with ALI. This study demonstrated that SQV prevented experimental ALI and improved glucocorticoid insensitivity by modulating the HMGB1/TLR4 pathway.
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