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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: INFLAMMOPHARMACOLOGY; v. 24, n. 2-3, p. 97-107, JUN 2016.
• Web of Science Citations: 13

Abstract

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)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Projects - Thematic Grants