Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-kappa B and oxidative stress

Autor(es):Mostrar menos -

Pinho-Ribeiro, Felipe A. ^[1] ; Fattori, Victor ^[1] ; Zarpelon, Ana C. ^[1] ; Borghi, Sergio M. ^[1] ; Staurengo-Ferrari, Larissa ^[1] ; Carvalho, Thacyana T. ^[1] ; Alves, Jose C. ^[1] ; Cunha, Fernando Q. ^[1] ; Cunha, Thiago M. ^[2] ; Casagrande, Rubia ^[3] ; Verri, Waldiceu A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Londrina, Dept Ciencias Patol, Ctr Ciencias Biol, Rod Celso Garcia Cid PR445 KM380, BR-86057970 Londrina, Parana - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Estadual Londrina, Univ Hosp, Dept Ciencias Farmaceut, Ctr Ciencias Saude, Av Robert Koch 60, BR-86038350 Londrina, Parana - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INFLAMMOPHARMACOLOGY; v. 24, n. 2-3, p. 97-107, JUN 2016.
• Citações Web of Science: 13

Resumo

We evaluated the effect of pyrrolidine dithiocarbamate (PDTC) in superoxide anion-induced inflammatory pain. Male Swiss mice were treated with PDTC and stimulated with an intraplantar or intraperitoneal injection of potassium superoxide, a superoxide anion donor. Subcutaneous PDTC treatment attenuated mechanical hyperalgesia, thermal hyperalgesia, paw oedema and leukocyte recruitment (neutrophils and macrophages). Intraplantar injection of superoxide anion activated NF-kappa B and increased cytokine production (IL-1 beta, TNF-alpha and IL-10) and oxidative stress (nitrite and lipid peroxidation levels) at the primary inflammatory foci and in the spinal cord (L4-L6). PDTC treatment inhibited superoxide anion-induced NF-kappa B activation, cytokine production and oxidative stress in the paw and spinal cord. Furthermore, intrathecal administration of PDTC successfully inhibited superoxide anion-induced mechanical hyperalgesia, thermal hyperalgesia and inflammatory response in peripheral foci (paw). These results suggest that peripheral stimulus with superoxide anion activates the local and spinal cord oxidative- and NF-kappa B-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Temático