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Author: Jesús Beltrán-García x

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Oxidative stress leads to severe phenotypes in sepsis through activation of NLRP3-pyroptosis

Jesús Beltrán-García

Jesús Beltrán-García Center for Biomedical Research Network on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Valencia, Spain
Biomedical Research Institute INCLIVA, Valencia, Spain
Department of Physiology, Medicine and Dentistry School, University of Valencia, Valencia, Spain

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Rebeca Osca-Verdegal

Rebeca Osca-Verdegal Center for Biomedical Research Network on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Valencia, Spain
Biomedical Research Institute INCLIVA, Valencia, Spain
Department of Physiology, Medicine and Dentistry School, University of Valencia, Valencia, Spain

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José Luis García-Giménez

José Luis García-Giménez Center for Biomedical Research Network on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Valencia, Spain
Biomedical Research Institute INCLIVA, Valencia, Spain
Department of Physiology, Medicine and Dentistry School, University of Valencia, Valencia, Spain

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Federico V. Pallardó

Federico V. Pallardó Center for Biomedical Research Network on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Valencia, Spain
Biomedical Research Institute INCLIVA, Valencia, Spain
Department of Physiology, Medicine and Dentistry School, University of Valencia, Valencia, Spain

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Oxidative stress is an important contributor to sepsis and one of the most important causes of death in intensive care units. Even though sepsis pathogenesis remains obscure due to its heterogenicity and complexity, there is increasing evidence that oxidants and antioxidants play a key role in its onset and progression. Recent evidence suggests that pyroptosis is required for defense against bacterial infection, and it is active in several cell types during sepsis. One of the most relevant mediators of pyroptosis is the NLRP3 inflammasome, and the oxidative stress/NLRP3 signaling pathway is one of the main upstream signals involved in its activation. So, it is of special relevance to clarify how oxidative stress and antioxidants can modulate pyroptosis signals and therefore decrease the deleterious effects that both oxidative stress and pyroptosis-related cytokines can induce in the tissues during sepsis. Recent studies evaluating several antioxidants are promising, but further trials are needed to confirm their potential role as agents to block NLRP3 and mitigate the exacerbated inflammasome-related responses during sepsis.