{
  "abstract": "Importance\n\nSpironolactone, a steroidal aldosterone antagonist, is widely used as a diuretic and antihypertensive agent. Steroids have been known to promote thrombosis by directly increasing platelet count and activation and indirectly by increasing oxidative stress and suppressing nitric oxide synthesis. However, the effects of spironolactone on platelet activation remain unclear.Objective\n\nTo investigate the effects of spironolactone on platelet function and underlying signaling mechanisms.Methods\n\nPlatelet aggregation, dense granule secretion, thromboxane A₂ (TxA₂) generation, and protein phosphorylation were evaluated in platelets treated with spironolactone.Results\n\nSpironolactone significantly inhibited the secondary wave of platelet aggregation and dense granule secretion induced by 2-methylthioadenosine diphosphate (2-MeSADP). It is known that 2-MeSADP-induced secretion and the resultant secondary wave of aggregation depend on TxA₂-mediated positive feedback, suggesting a role for spironolactone in regulating TxA₂ generation in platelets. Additionally, spironolactone did not affect 2-MeSADP-induced platelet aggregation in aspirin-treated platelets in which TxA₂ generation was blocked. Furthermore, platelet aggregation and secretion induced by low concentrations of thrombin, which are also affected by TxA₂-mediated positive feedback, were partially inhibited by spironolactone. Notably, spironolactone significantly suppressed TxA₂ generation induced by both 2-MeSADP and thrombin. Finally, spironolactone markedly inhibited the 2-MeSADP- and thrombin-induced phosphorylation of cytosolic phospholipase A₂ (cPLA₂), extracellular signal-regulated kinase, and protein kinase B in non-aspirin-treated platelets, whereas only cPLA₂ phosphorylation was significantly inhibited in aspirin-treated platelets.Conclusions and relevance\n\nSpironolactone inhibits platelet activation by suppressing TxA₂ generation, primarily by modulating cPLA₂ phosphorylation, providing mechanistic insight into its effects on platelet signaling in vitro.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.",
    "Molecular Cardiology Research Institute, Tufts University School of Medicine, Boston, MA 02111, USA.",
    "Cancer Research Center, Chungbuk National University, Cheongju 28644, Korea. skim0026@cbu.ac.kr."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sanggu Kim",
      "orcid": "0000-0002-1030-5655"
    },
    {
      "affs": [
        1
      ],
      "name": "Preeti Kumari Chaudhary",
      "orcid": "0000-0002-9186-8336"
    },
    {
      "affs": [
        0
      ],
      "name": "Seongmo Yang",
      "orcid": "0009-0006-6838-7442"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Soochong Kim",
      "orcid": "0000-0002-6739-9787"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d238wdb8ccqex.bib",
  "cited_by": 0,
  "doi": "10.4142/jvs.26033",
  "fulltext_url": "https://europepmc.org/articles/PMC13655564",
  "id": "d238wdb8ccqex",
  "issns": [
    "1229-845X",
    "1976-555X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42847795",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2720|Platelet Disorders and Treatments"
    ]
  ],
  "openalex": "W7211914817",
  "pdf_url": "https://europepmc.org/articles/PMC13655564?pdf=render",
  "pmcid": "PMC13655564",
  "pmid": "42847795",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d238wdb8ccqex.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42847795",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42847795"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Platelet Disorders and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Antiplatelet effect of spironolactone via modulation of cPLA₂-mediated thromboxane A₂ generation in murine platelets.",
  "title_text": "Antiplatelet effect of spironolactone via modulation of cPLA₂-mediated thromboxane A₂ generation in murine platelets.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/d238wdb8ccqex",
  "venue": "Journal of veterinary science",
  "versions": []
}