Influência do receptor vanilóide tipo 1 (TRPV1) na endotoxemia

Abstract

Bacterial endotoxin presence in the bloodstream is associated with the onset and maintenance of sepsis, complex and heterogeneous condition that promotes the release of inflammatory mediators, which lead to changes in the central nervous system and subsequent unbalanced inflammatory immune response, with consequent multiple organ failure. The TRPV1 receptor, in turn, participate in the modulation of different systems and can influence physiological processes impaired by inflammation, and so represent a potential therapeutic target. The aim of the study was to evaluate the involvement of TRPV1 receptors in acute lung injury/ acute respiratory distress syndrome (ALI/ARDS) and in the sickness behavior induced by endotoxin, with the blockade by capsazepine (CPZ) in mice. Regarding the ALI/ARDS, animals had the disease induced by LPS 5.0mg/kg with simultaneous application of CPZ and were analyzed after 24 hours. Reduced resistance of the system and tissue was observed, in addition to decreased alveolar collapse by the blockade of TRPV1 receptors, showing a modulation by these receptors in the ALI/ARDS. Regarding sickness behavior, animals received CPZ administration 30 minutes before application of LPS 200 μg/kg, and after 2 hours were submitted to the behavioral tests and blood and tissues collection. The administration of blocker attenuated the anxious and depressive-like effects, the increased body temperature and the c-fos expression in some brain areas induced by LPS. However, CPZ did not promote changes in mobility, food intake, weight gain, plasma levels of cytokines and protein expression in the hippocampus and hypothalamus. These results suggest the involvement of TRPV1 receptors in the modulation of sickness behavior, in regulating body temperature and respiratory mechanics after immune challenge.