TY - JOUR
T1 - Vitamin B6 Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis
T2 - Involvement of the Kynurenine Pathway Modulation
AU - Danielski, Lucinéia Gainski
AU - Giustina, Amanda Della
AU - Goldim, Mariana Pereira
AU - Florentino, Drielly
AU - Mathias, Khiany
AU - Garbossa, Leandro
AU - de Bona Schraiber, Rosiane
AU - Laurentino, Ana Olívia Martins
AU - Goulart, Marina
AU - Michels, Monique
AU - de Queiroz, Karina Barbosa
AU - Kohlhof, Markus
AU - Rezin, Gislaine Tezza
AU - Fortunato, Jucélia Jeremias
AU - Quevedo, Joao
AU - Barichello, Tatiana
AU - Dal-Pizzol, Felipe
AU - Coimbra, Roney S.
AU - Petronilho, Fabricia
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250–300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B6, CLP + saline, and CLP + vit B6 (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B6 interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B6 exerts neuroprotective effects in acute and late consequences after sepsis.
AB - Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250–300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B6, CLP + saline, and CLP + vit B6 (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B6 interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B6 exerts neuroprotective effects in acute and late consequences after sepsis.
KW - Brain damage
KW - Neuroinflammation
KW - Oxidative stress
KW - Sepsis
KW - Tryptophan
KW - Vitamin B
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U2 - 10.1007/s12035-017-0706-0
DO - 10.1007/s12035-017-0706-0
M3 - Article
C2 - 28879460
AN - SCOPUS:85028839237
SN - 0893-7648
VL - 55
SP - 5255
EP - 5268
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 6
ER -