A curcumina atenua os déficits cognitivos e o estresse oxidativo em animais sobreviventes a sepse

Abstract

Sepsis is characterized by a set of systemic reactions in response to the infectious agent. Its clinical outcome induces irreversible brain lesions, which may culminate in long-term cognitive damage in sepsis surviving patients. The neuroprotective property of long Turmeric (curcumin) has been widely investigated in several neuropsychiatric disorders. In this perspective, the present study proposed to evaluate the effect of curcumin on cognitive and neurodegenerative alterations induced by sepsis. Initially, we randomly divided male Wistar rats into two experimental groups: control (Sham) and septic (CLP), which were submitted to cecal ligation and puncture sugery to induce sepsis. The characterization of cognitive behavior was performed 10, 20 or 30 days after the induction of sepsis through open field, object recognition and Morris water maze behavioral tests. Anotherset of animals was submitted to cecal ligation and puncture surgery and treated by gavage with vehicle or curcumin (50 mg/kg) for seven consecutive days. Cognitive impairment was evaluated on the tenth day after induction of sepsis through the behavioral tests already mentioned. Immediately after the end of the behavioral tests, the animals were sacrificed and their hippocampus was dissected for evaluation of redox status through the levels of ROS (by lucigenin allocated fluorescence method), protein nitrosilation, trap percentage, TBARS, free and total GSH and GSSG (by s-nitrosotiol residue capture method). As a result of the characterization of cognitive behavior, a marked cognition deficit as well as deficits in the recognition and spatial memories were observed 10 days after the induction of sepsis, which remained in a time-dependent manner to this clinical condition, These deficts were characterized by the increase in exploration time of the familiar object and a reduction in exploration time of the new object and the recognition index after 2 and 24 h in the object recognition test. Also, by the increased latency to reach the platform and to reach the target quadrant and by the reduced length of stay in the target quadrant in the Morris water maze test, when compared to the Sham group. As for the animals that received oral treatment with curcumin (50 mg/kg), a significant reduction in cognitive deficits and recognition and spatial memories impairments was observed 10 days after the induction of sepsis when compared to the CLP+vehicle group. In addition, intense oxidative stress was observed in animals from the CLP+vehicle group, indicated by the expressive increase of ROS, protein nitrosilation and TBARS, and by the reduction of the antioxidant parameters Trap and free and total GSH when compared to the control group. Treatment with curcumin was effectively able to attenuate these parameters when compared to the CLP animals treated with vehicle. The analysis of the GSSG parameter showed no statistically significant difference between the tested groups.