Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties
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- 作者：José Christian Machado Ximenes (3)
Danilo de Oliveira Gon?alves (1)
Rafaelly Maria Pinheiro Siqueira (1)
Kelly Rose Tavares Neves (1)
Gilberto Santos Cerqueira (1)
Alyne Oliveira Correia (2)
Francisco Hélder Cavalcante Félix (4)
Luzia Kalyne Almeida Moreira Leal (1)
Gerly Anne de Castro Brito (1)
Maria da Gra?a Naffah-Mazzacorati (3)
Glauce Socorro de Barros Viana (1) (2) (5) - 关键词：Valproic acid/sodium valproate ; Inflammation ; Nociception ; Cytokines
- 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
- 出版年：2013
- 出版时间：July 2013
- 年：2013
- 卷：386
- 期：7
- 页码：575-587
- 全文大小：1473KB
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Danilo de Oliveira Gon?alves (1)
Rafaelly Maria Pinheiro Siqueira (1)
Kelly Rose Tavares Neves (1)
Gilberto Santos Cerqueira (1)
Alyne Oliveira Correia (2)
Francisco Hélder Cavalcante Félix (4)
Luzia Kalyne Almeida Moreira Leal (1)
Gerly Anne de Castro Brito (1)
Maria da Gra?a Naffah-Mazzacorati (3)
Glauce Socorro de Barros Viana (1) (2) (5)
3. Federal University of S?o Paulo, S?o Paulo (UNIFESP), S?o Paulo, Brazil
1. Faculty of Medicine of the Federal University of Ceará (UFC), Fortaleza, Brazil
2. Faculty of Medicine Estácio of Juazeiro do Norte (FMJ), Ceará, Brazil
4. Albert Sabin Hospital, Fortaleza, Brazil
5. Rua Barbosa de Freitas, 130/1100, Fortaleza, Brazil - ISSN：1432-1912
文摘
Valproic acid (VA) is a major antiepileptic drug, used for several therapeutic indications. It has a wide activity spectrum, reflecting on mechanisms of action that are not fully understood. The objectives of this work were to study the effects of VA on acute models of nociception and inflammation in rodents. VA (0.5, 1, 10, 25, and 50?mg/kg, p.o.) effects were evaluated on the carrageenan-induced paw edema, carrageenan-induced peritonitis, and plantar tests in rats, as well as by the formalin test in mice. The HE staining and immunohistochemistry assay for TNF-α in carrageenan-induced edema, from paws of untreated and VA-treated rats, were also carried out. VA decreased paw edema after carrageenan, and maximum effects were seen with doses equal to or higher than 10?mg/kg. VA also preserved the tissue architecture as assessed by the HE staining. Immunohistochemical studies revealed that VA significantly reduced TNF-α immunostaining in carrageenan-inflamed rat paws. In addition, the anti-inflammatory action of VA was potentiated by pentoxifylline (a phosphodiesterase inhibitor, known to inhibit TNF-α production), but not by sodium butyrate or by suberoylanilide hydroxamic acid (SAHA), nonspecific and specific inhibitors, respectively, of histone deacetylase. However, the decrease in the number of positive TNF-α cells in the rat paw was drastically potentiated in the VA-?SAHA associated group. VA also reduced leukocytes and myeloperoxidase (MPO) releases to the peritoneal exudate, in the carrageenan-induced peritonitis. Although in the formalin test, VA inhibited both phases, the inhibition was mainly on the second phase. Furthermore, VA significantly increased the reaction time to thermal stimuli, as assessed by the plantar test. VA is a multi-target drug, presenting potent antinociceptive and anti-inflammatory properties at a lower dose range. These effects are partly dependent upon its inhibitory action on TNF-α-related pathways. However, the participation of the HDAC inhibition with the VA anti-inflammatory action cannot be ruled out. Inflammatory processes are associated with free radical damage and oxidative stress, and their blockade by VA could also explain the present results.