Cardioprotective effects of dehydroisohispanolone through inhibition of NLRP3 inflammasome in cardiomyocytes

• Fernández Vega, Eva ^[1] ; Cuadrado, Irene ^[1] ; Heras, Beatriz de las ^[1] ; Hortelano, Sonsoles ^[2]
  1. [1] Universidad Complutense de Madrid

     Universidad Complutense de Madrid

     Madrid, España

     
  2. [2] Instituto de Investigación de Enfermedades Raras

     Instituto de Investigación de Enfermedades Raras

     Madrid, España

     
• Localización: Dianas: revista de dianas terapéuticas, ISSN-e 1886-8746, Vol. 13, Nº. 1, 2024 (Ejemplar dedicado a: Actas del IX Congreso de Señalización Celular, SECUAH 2024 / coord. por María José Carmena Sierra, Alberto Domingo Galán)
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Doxorubicin (DOX) is an anthracycline antineoplasic drug widely prescribed to treat various human haematological and solid cancers. However, its cardiotoxicity has limited its clinical use. Accumulating evidence supports that inflammasomes play a pivotal role in the progression of myocardial injury as occurs with DOX-induced cardiotoxicity. As an innate immune signaling complex, NLRP3 inflammasome can be activated by DOX and triggers the secretion of proinflammatory cytokines IL-1β and IL-18 and pyroptotic cell death. Therefore, targeting the inflammatory response mediated by the NLRP3 inflammasome could be a promising therapeutic strategy to overcome this problem. In the search for new therapeutic strategies for cardioprotection, diterpenes are a good starting point, since a large number of them have shown anti-inflammatory and cardioprotective properties, especially labdane diterpenes. In particular, the diterpene dehydroisohispanolone (DIH) derived from hispanolone, had previously shown these properties against myocardial infarction, and recently, it has been reported as an NLRP3 inhibitor. The present study aimed to assess if DIH treatment could alleviate DOX-induced toxicity, in H9C2 and AC16 cell lines (rat and human cardiomyocytes, respectively). DIH significantly attenuated DOX-induced cardiotoxicity, as cell viability was increased by up to 70%. Moreover, IL-1β and IL-18 levels were significantly decreased after treatment with DIH. Finally, reduction of pyroptosis, measured in terms of lactate dehydrogenase (LDH) release, was also observed.