Curcumin prevents sickness behavior and fever by the modulation of Nrf2 activity in a model of endotoxemia

Abstract Lipopolysaccharide (LPS) is a potent inducer of inflammation, triggering behavioral changes and fever. The present study aimed to evaluate whether pretreatment with curcumin prevents the behavioral changes and fever induced by LPS through the modulation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Male Wistar rats were pretreated for 2 consecutive days with vehicle or curcumin at doses of 25, 50, or 100 mg/kg by oral gavage. The animals intraperitoneally received either vehicle or LPS at a dose of 500 µg/kg. After 2 h, the behavioral responses were assessed through open field test (OFT), social interaction test, forced swim test (FST), and food intake assessment. The febrile response was assessed by telemetry after vehicle or LPS injection to evaluate the effect of curcumin on the thermoregulatory response during the immunological challenge. The pretreatment with curcumin at doses of 50 and 100 mg/kg prevented the reduction of distance traveled on OFT, increased the immobility time of FST, impaired social withdrawal, decreased food intake, and induced fever. In addition, at these doses, it was possible to observe a significant decrease in the plasma levels of TNF-α and IL1-β and an increase in Nrf2 translocation to the cell nucleus during the immunological challenge. Our data provide further evidence of curcumin's ability to prevent LPS-induced sickness behavior and fever possibly by a mechanism related to the modulation of Nrf2 translocation.