Recent studies have demonstrated that NF-kappaB and oxidative stress contributes to secondary injury after impacted injury to the rat spinal cord. We postulated that pyrrolidine dithiocarbamate (PDTC), antioxidant which is potent inhibitor of NF-kappaB, would attenuate NF-kappaB-related inflammatory and oxidative events which occur after spinal cord injury. Spinal cord injury was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8 laminectomy. Here we have investigated the effects of pyrrolidine dithiocarbamate (30mg/kg, 30 min before spinal cord injury and 6h after SCI) on the levels of myeloperoxidase (MPO) activity; on the levels of Malondialdehyde (MDA) in the damaged tissue. Western blot analysis was performed to assess the cytoplasmic levels of IkappaB-alpha. PDTC exerted potent anti-inflammatory effects with significant reduction of (A) polymorphonuclear cell infiltration, (B) lipid peroxidation, and furthermore it significantly prevented the activation of NFkappaB (EMSA and immunoblots).
Pyrrolidine dithiocarbamate reduced spinal cord trauma in rats
GENOVESE, TIZIANA;CARDALI, Salvatore Massimiliano;CONTI, Alfredo;CUZZOCREA, Salvatore
2004-01-01
Abstract
Recent studies have demonstrated that NF-kappaB and oxidative stress contributes to secondary injury after impacted injury to the rat spinal cord. We postulated that pyrrolidine dithiocarbamate (PDTC), antioxidant which is potent inhibitor of NF-kappaB, would attenuate NF-kappaB-related inflammatory and oxidative events which occur after spinal cord injury. Spinal cord injury was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8 laminectomy. Here we have investigated the effects of pyrrolidine dithiocarbamate (30mg/kg, 30 min before spinal cord injury and 6h after SCI) on the levels of myeloperoxidase (MPO) activity; on the levels of Malondialdehyde (MDA) in the damaged tissue. Western blot analysis was performed to assess the cytoplasmic levels of IkappaB-alpha. PDTC exerted potent anti-inflammatory effects with significant reduction of (A) polymorphonuclear cell infiltration, (B) lipid peroxidation, and furthermore it significantly prevented the activation of NFkappaB (EMSA and immunoblots).Pubblicazioni consigliate
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