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

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-κB and increased cytokine production (IL-1β, TNF-α 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-κB 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-κB-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.

Topical emulsion containing pyrrolidine dithiocarbamate: effectiveness against ultraviolet B irradiation-induced injury of hairless mouse skin

“…Herein, EcPDTC reduced TNF‐α and IL‐1β production. In line with our results, the PDTC treatment reduces TNF‐α and IL‐1β levels in mice with dextran sodium sulfate‐induced colitis, and with superoxide anion‐induced pain and inflammation . This inhibition of pro‐inflammatory cytokine production explains the observation that the EcPDTC reduced UVB radiation‐induced skin oedema, MPO activity, MMP‐9 activity, collagen degradation, mast cell and sunburn cell counts .…”

“…PDTC is a low‐molecular‐weight thiol compound with great therapeutic potential as an anti‐inflammatory and antioxidant . PDTC was initially regarded as a potent inhibitor of NF‐κB, and it has been studied as a strong antioxidant compound to counteract the toxic effects of ROS . The antioxidant potential of PDTC is primarily due to its thiol group, which neutralizes ROS .…”

“…Topical delivery of antioxidant and anti‐inflammatory molecules is considered a promising strategy to reduce UVB irradiation‐induced skin damages . Pyrrolidine dithiocarbamate (PDTC) is a small molecule with relatively low cost though with important pharmacological activity such as antioxidant and anti‐inflammatory . Preclinical toxicity study has shown that PDTC is a safe drug .…”

“…Preclinical toxicity study has shown that PDTC is a safe drug . PDTC has been shown to inhibit NF‐κB activation . Our previous data showed that intraperitoneal treatment with PDTC inhibits UVB irradiation‐stimulated skin inflammation and oxidative stress by inhibiting I‐κB degradation and consequent NF‐κB activation in keratinocytes .…”

“…[45] PDTC has been shown to inhibit NF-jB activation. [27,40,43,44,[46][47][48] Our previous data showed that intraperitoneal treatment with PDTC inhibits UVB irradiation-stimulated skin inflammation and oxidative stress by inhibiting I-jB degradation and consequent NF-jB activation in keratinocytes. [27] However, it remains to be determined whether PDTC can effectively inhibit UVB irradiation-induced injury as a cutaneous treatment with broader dermatological perspective of applicability than intraperitoneal route of administration.…”