Efeito da curcumina sobre as alterações comportamentais e termorregulatórias durante o desafio imunológico com lipopolissacarídeo

Abstract

During an infectious process, in addition to the thermoregulatory changes it’s possible to observe behavioral responses such as decreased locomotion and sociability, reduced food intake, anorexia and anhedonia, witch together are called Sickness Behavior. Lipolysaccharide (LPS) is a molecular component of the cell wall of gram negative bacteria, which’s able to activated the immune system mimicking an inflammatory-infectious process, culminating in the unhealthy behavior. The functional properties of Cúrcuma longa (curcumin) have been extensively investigated, these effects being beyond its nutritional property. Among them we can mention: its anti-inflammatory, anti-depressive, neuroprotective, anticarcinogenic and antioxidant action. In view of the above, the objective of the present study was to investigate the influence of curcumin on the disease behavior induced by LPS. Initially, we pre-treated Wistar rats for 2 consecutive days with vehicle or curcumin at doses of 25, 50 or 100mg/Kg through gavage (p.o). Then, 1 hour after the second dose of vehicle or curcumin, the animals received either intraperonially (i.p), vehicle or LPS at the dose of 500μg/Kg and the behavioral responses were assessed after 2 hours. In the animals of the curcumin group (50 and 100mg/Kg)+LPS, we observed an increase in the exploratory behavior (in the open field, sociability (in the social interaction test) and food intake as well as the prevention of increased immobility time induced by LPS (in the forced swimming test) when compared to group V+LPS. However, the same could not be observed in animals receiving curcumin at a dose of 25mg/Kg, p.o, prior to LPS administration, as compared to the control. Interestingly, all doses of curcumin tested were able to decrease the plasma concentrations of the proinflammatory cytokines TNF-α and IL1-β induced by LPS after 2 hours of application. Reagargin thermoregulation, our results showed that the animals receiving V+LPS and curcumin 25mg/Kg+LPS presented a fever onset 2 hours after endotoxin administration and persisted at the following hours. It was also possible to note the prevetion of LPS-iduced fever in animals receiving pre-treatment with curcumin at doses of 50 and 100mg/Kg. In view of this information, we suggest that pre-treatment with curcumin 50 and 100mg/Kg in endotoxemic animals was able to prevent unhealthy behavior, as well as reduced plasma levels of TNF-α and IL1-β and prevent fever, possibly by inhibiting LPSinduced cytokine synthesis and release.