Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture.
Oxidative stress plays an important role in the development of cognitive impairment in sepsis. Here we assess the effects of acute and extended administration of cannabidiol (CBD) on oxidative stress parameters in peripheral organs and in the brain, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent either sham operation or CLP. Rats subjected to CLP were treated by intraperitoneal injection with "basic support" and CBD (at 2.5, 5, or 10mg/kg once or daily for 9days after CLP) or vehicle. Six hours after CLP (early times), the rats were killed and samples from lung, liver, kidney, heart, spleen, and brain (hippocampus, striatum, and cortex) were obtained and assayed for thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. On the 10th day (late times), the rats were submitted to the inhibitory avoidance task. After the test, the animals were killed and samples from lung, liver, kidney, heart, spleen, and brain (hippocampus) were obtained and assayed for TBARS formation and protein carbonyls. The acute and extended administration of CBD at different doses reduced TBARS and carbonyl levels in some organs and had no effects in others, ameliorated cognitive impairment, and significantly reduced mortality in rats submitted to CLP. Our data provide the first experimental demonstration that CBD reduces the consequences of sepsis induced by CLP in rats, by decreasing oxidative stress in peripheral organs and in the brain, improving impaired cognitive function, and decreasing mortality.
Cassol
Omar J
OJ
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Comim
Clarissa M
CM
Silva
Bruno R
BR
Hermani
Fernanda V
FV
Constantino
Larissa S
LS
Felisberto
Francine
F
Petronilho
Fabricia
F
Hallak
Jaime Eduardo C
JE
De Martinis
Bruno S
BS
Zuardi
Antonio W
AW
Crippa
José A S
JA
Quevedo
João
J
Dal-Pizzol
Felipe
F
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002185:Cannabidiol / Q000627:therapeutic use*; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology*; D050050:Protein Carbonylation / Q000187:drug effects; D011677:Punctures / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications* / Q000209:etiology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D017392:Thiobarbituric Acid Reactive Substances; D002185:Cannabidiol