Neuroprotective effects of valproic acid on brain ischemia are related to its HDAC and GSK3 inhibitions.

Autor: Silva MR; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil; Faculty of Medicine of the Federal University of Ceará (UFC), Fortaleza, Brazil., Correia AO; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil., Dos Santos GCA; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil., Parente LLT; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil., de Siqueira KP; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil., Lima DGS; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil., Moura JA; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil., da Silva Ribeiro AE; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil., Costa RO; Faculty of Medicine of the Federal University of Ceará (UFC), Fortaleza, Brazil., Lucetti DL; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil; Faculty of Medicine of the Federal University of Ceará (UFC), Fortaleza, Brazil., Lucetti ECP; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil., Neves KRT; Faculty of Medicine of the Federal University of Ceará (UFC), Fortaleza, Brazil., de Barros Viana GS; Faculty of Medicine Estácio of Juazeiro do Norte (Estácio FMJ), Juazeiro do Norte, Brazil; Faculty of Medicine of the Federal University of Ceará (UFC), Fortaleza, Brazil. Electronic address: glauce.viana@pq.cnpq.br.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2018 Apr; Vol. 167, pp. 17-28. Date of Electronic Publication: 2018 Feb 13.
DOI: 10.1016/j.pbb.2018.02.001
Abstrakt: Valproic acid (VA) is an antiepileptic that is also used for the treatment of bipolar disorders. The objective was to evaluate the neuroprotective effects of VA on a brain ischemia model. The groups of male Wistar rats were: SO (sham-operated), ischemic and ischemic treated with VA (25, 50 and 100 mg/kg, p.o.). After anesthesia with ketamine and xilazine, the animals were subjected to clamping of carotid arteries (30 min) and reperfusion. Except for the carotid clamping, the SO group was submitted to the same procedure. On the 7th day, the animals were behaviorally evaluated, euthanized and had their brain dissected for neurochemical and immunohistochemical assays. The data were analyzed by ANOVA and Tukey as the post hoc test. The results showed that VA reversed partly or completely the behavioral (locomotor activity and memory deficits), neurochemical (striatal DA and DOPAC levels, brain nitrite and lipid peroxidation) and immunohistochemical alterations (iNOS, COX-2, HDAC and GSK3) observed in the untreated ischemic group. VA neuroprotective effects are probably related to its anti-inflammatory and antioxidant properties, as well as to HDAC and GSK3 inhibitory effects. These findings stimulate translational studies focusing on VA as a neuroprotective drug to be potentially used in the clinic for several neurological conditions.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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