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Oxid Med Cell Longev ; 2020: 8820651, 2020.
Article in English | MEDLINE | ID: mdl-33381269

ABSTRACT

Sepsis is characterized by a dysregulated immune response to infection characterized by an early hyperinflammatory and oxidative response followed by a subsequent immunosuppression phase. Although there have been some advances in the treatment of sepsis, mortality rates remain high, urging for the search of new therapies. ß-Lapachone (ß-Lap) is a natural compound obtained from Tabebuia avellanedae Lorentz ex Griseb. with several pharmacological properties including bactericidal, anti-inflammatory, and antioxidant activity. Thus, the aim of this study was to evaluate the effects of ß-Lap in a mouse sepsis model. To this, we tested two therapeutic protocols in mice submitted to cecal ligation and puncture- (CLP-) induced sepsis. First, we found that in pretreated animals, ß-Lap reduced the systemic inflammatory response and improved bacterial clearance and mouse survival. Moreover, ß-Lap also decreased lipid peroxidation and increased the total antioxidant capacity in the serum and peritoneal cavity of septic animals. In the model of severe sepsis, the posttreatment with ß-Lap was able to increase the survival of animals and maintain the antioxidant defense function. In conclusion, the ß-Lap was able to increase the survival of septic animals by a mechanism involving immunomodulatory and antioxidant protective effects.


Subject(s)
Naphthoquinones/therapeutic use , Sepsis/drug therapy , Sepsis/mortality , Animals , Anti-Inflammatory Agents/therapeutic use , Chemoprevention/methods , Cytokines/metabolism , Disease Models, Animal , Immunosuppression Therapy/methods , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/mortality , Inflammation Mediators/metabolism , Male , Mice , Oxidative Stress/drug effects , Sepsis/metabolism , Sepsis/pathology , Survival Rate
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