Amelioration of Neurochemical Alteration and Memory and Depressive Behavior in Sepsis by Allopurinol, a Tryptophan 2,3-Dioxygenase Inhibitor.

BACKGROUND: In response to inflammation and other stressors, tryptophan is catalyzed by Tryptophan 2,3-Dioxygenase (TDO), which leads to activation of the kynurenine pathway. Sepsis is a serious condition in which the body responds improperly to an infection, and the brain is the inflammation target in this condition. OBJECTIVE: This study aimed to determine if the induction of TDO contributes to the permeability of the Blood-Brain Barrier (BBB), mortality, neuroinflammation, oxidative stress, and mitochondrial dysfunction, besides long-term behavioral alterations in a preclinical model of sepsis. METHODS: Male Wistar rats with two months of age were submitted to the sepsis model using Cecal Ligation and Perforation (CLP). The rats received allopurinol (Allo, 20 mg/kg, gavage), a TDO inhibitor, or a vehicle once a day for seven days. RESULTS: Sepsis induction increased BBB permeability, IL-6 level, neutrophil infiltrate, nitric oxide formation, and oxidative stress, resulting in energy impairment in 24h after CLP and Allo administration restored these parameters. Regarding memory, Allo restored short-term memory impairment and decreased depressive behavior. However, no change in survival rate was verified. CONCLUSION: In summary, TDO inhibition effectively prevented depressive behavior and memory impairment 10 days after CLP by reducing acute BBB permeability, neuroinflammation, oxidative stress, and mitochondrial alteration.

Iota-carrageenan/xyloglucan/serine powders loaded with tranexamic acid for simultaneously hemostatic, antibacterial, and antioxidant performance.

This study sought to prepare powder hemostats based on iota-carrageenan (ιC), xyloglucan (XYL), l-serine (SER), and tranexamic acid (TA). The powder form was chosen because it enables the hemostat to be used in wounds of any shape and depth. The powder hemostats showed irregular shapes and specific surface areas ranging from 34 to 46 m2/g. Increasing TA amount decreases the specific surface area, bulk density, water and blood absorption, and the antibacterial activities of the powder hemostats, but not the water retention ability. Conversely, in vitro biodegradation was positively impacted by increasing the TA content in the powder hemostats. In both the in vitro and in vivo tests, powder hemostats showed reduced bleeding time, significant adhesion of red blood cells, great hemocompatibility, moderate antioxidant activity, and high biocompatibility. These findings shed new light on designing powder hemostats with intrinsic antibacterial and antioxidant activity and excellent hemostatic performance.