[en] Peritoneal dialysis (PD) is a renal replacement therapy that has similar results in terms of efficacy to hemodialysis at a lower cost. Its main disadvantage is that the continuous contact of dialysis fluids with the peritoneal membrane promotes oxidative stress and inflammation of the peritoneum, leading to structural alterations such as epithelial-tomesenchymal transition that can lead to the failure of the technique. Because oxidative stress is essential to the development of peritoneal damage, mitochondria may play a key role in the pathophysiology of the peritoneum as they are the main source of reactive oxygen species (ROS). These compounds may act as Damage-Associated Molecular Patterns (DAMPs) by activating the NLRP3 inflammasome, which triggers the activation of caspase 1 and the consequent IL-1β and IL-18 secretion, which trigger the inflammatory response. For this reason, the aim of this study was to assess the role of mitochondria in inflammasome activation by studying the effect of mitochondrial dysfunction on caspase 1 activation. To this end, a descriptive analysis of caspase 1 expression in mesothelial cells from the peritoneal effluent of patients on PD therapy was performed. First, a link between mitochondrial damage and the inflammasome was observed, as mitochondrial dysfunction induced per se an increase in caspase 1 protein expression in mesothelial cells from peritoneal effluent. Furthermore, it was also observed that the proinflammatory cytokine TNF-α has the ability to increase caspase 1 activation. Related to the mediators involved, the NLRP3 inflammasome and ROS from mitochondria were shown to be implicated in inflammasome activation. Finally, the effect of the natural antioxidant resveratrol was tested, and we found that prevents caspase 1 activation induced by mitochondrial dysfunction and proinflammatory cytokines. These results could contribute to a better understanding of the development of the inflammatory response in the peritoneum during PD treatment and could help in the search for new therapeutic targets.

[gl] A diálise peritoneal (DP) é unha tratamento de substitución renal que, en termos de eficacia, ten resultados similares aos da hemodiálise a un custo inferior. A súa principal desvantaxe é que o contacto continuo dos fluídos de diálise coa membrana peritoneal favorece o estrés oxidativo e a inflamación do peritoneo, provocando alteracións estruturais como a transición epitelio-mesenquimal que poden levar ao fracaso da técnica. Dado que o estrés oxidativo é esencial no desenvolvemento do dano peritoneal, as mitocondrias poderían desempeñar un papel fundamental na fisiopatoloxía do peritoneo ao ser a fonte principal de especies reactivas de osíxeno (ROS). Estes compostos poden actuar como padróns moleculares asociados ao dano (DAMPs; do inglés: Damage-Associated Molecular Patterns) activando o inflamasoma NLRP3, que provoca a activación da caspasa 1 e a conseguinte secreción de IL-1β e IL-18, desencadeantes da resposta inflamatoria. Por este motivo, o obxectivo deste traballo foi avaliar o papel da mitocondria na activación do inflamasoma mediante o estudo do efecto da disfunción mitocondrial na activación de caspasa 1. Para iso, realizouse unha análise descritiva da expresión de caspasa 1 en células mesoteliais procedentes do efluente peritoneal de pacientes en terapia de PD. En primeiro lugar, observouse que existe unha relación entre o dano mitocondrial e o inflamasoma, xa que a disfunción mitocondrial per se induciu un aumento da expresión proteica de caspasa 1 nas células mesoteliais do efluente peritoneal. Así mesmo, tamén se observou que a citoquina proinflamatoria TNF-α ten a capacidade de aumentar a activación de caspasa 1. En canto aos mediadores implicados, mostrouse que o inflamasoma NLRP3 e os ROS procedentes da mitocondria están implicados na activación do inflamasoma. Finalmente, probouse o efecto do antioxidante natural resveratrol e observouse que impide a activación de caspasa 1 inducida pola disfunción mitocondrial e citoquinas proinflamatorias. Estes resultados poderían contribuír a obter unha mellor comprensión do desenvolvemento da resposta inflamatoria no peritoneo durante o tratamento con DP e, polo tanto, axudar na busca de novas dianas terapéuticas.