Effects of organoselenium compounds on early and late brain biochemical alterations in sepsis-survivor rats.
Studies have consistently reported the participation of oxidative stress, energetic metabolism impairment, and creatine kinase (CK) activity alterations in rat brain in early times in an animal model of sepsis and persist for up to 10 days. We have assessed the antioxidant effects of administration of Ebselen (Eb) e diphenyl diselenide (PhSe)2 two organoselenium compounds on brain oxidative stress, energetic metabolism, and CK activity 12, 24 h, and 10 days after sepsis by cecal ligation and perforation (CLP) in rats. Male Wistar rats underwent either sham operation or CLP and were treated with oral injection of Eb (50 mg/kg) or (PhSe)2 (50 mg/kg) or vehicle. 12, 24 h, and 10 days after CLP, the rats were sacrificed, and samples from brain (hippocampus, striatum, cerebellum, prefrontal cortex, and cortex) were obtained and assayed for thiobarbituric acid reactive species and protein carbonyls formation, mitochondrial respiratory chain, and CK activity. We observed in the results a reduction of oxidative damage to lipids and proteins in the different cerebral structures studied and times with the administration of (PhSe)2; however, Eb seems to exert the same effect. Such changes are reflected in the assessment of mitochondrial respiratory chain complexes by reversing the decreased activity of the complex caused by the model of CLP and CK activity. Our data provide the first experimental demonstration that (PhSe)2 was able to reduce the brain dysfunction associated with CLP-induced sepsis in rats, by decreasing oxidative stress parameters mitochondrial dysfunction and CK activity in early times and in late time.
Graduate Program in Health Sciences, Clinical and Experimental Pathophysiology Laboratory - FICEXP, Universidade do Sul de Santa Catarina (UNISUL), Tubarão, SC, 88704-900, Brazil.
Fernanda
F
Silvestre
Lucinéia Gainski
LG
Danielski
Monique
M
Michels
Drielly
D
Florentino
Andriele
A
Vieira
Luana
L
Souza
Larissa Colonetti
LC
Cardoso
Rosiane
R
Schraiber
Gislaine Tezza
GT
Rezin
Francieli
F
Vuolo
Joao Batista
JB
da Rocha
Tatiana
T
Barichello
João
J
Quevedo
Felipe
F
Dal-Pizzol
Fabricia
F
Petronilho
D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D054833:Isoindoles; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D011897:Random Allocation; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001393:Azoles; D001555:Benzene Derivatives; D045222:Electron Transport Chain Complex Proteins; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; C042986:ebselen; D003402:Creatine Kinase