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Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats
Increased reactive oxygen species by the activation of NADPH oxidase (NOX) contributes to the development of diabetic complications. Apocynin, a NOX inhibitor, increases sciatic nerve conductance and blood flow in diabetic rats. We investigated potential protective effect of apocynin in rat diabetic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126136/ https://www.ncbi.nlm.nih.gov/pubmed/30127129 http://dx.doi.org/10.4103/1673-5374.232530 |
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author | Olukman, Murat Önal, Aytül Çelenk, Fatma Gül Uyanıkgil, Yiğit Çavuşoğlu, Türker Düzenli, Neslihan Ülker, Sibel |
author_facet | Olukman, Murat Önal, Aytül Çelenk, Fatma Gül Uyanıkgil, Yiğit Çavuşoğlu, Türker Düzenli, Neslihan Ülker, Sibel |
author_sort | Olukman, Murat |
collection | PubMed |
description | Increased reactive oxygen species by the activation of NADPH oxidase (NOX) contributes to the development of diabetic complications. Apocynin, a NOX inhibitor, increases sciatic nerve conductance and blood flow in diabetic rats. We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level. Rat models of streptozotocin-induced diabetes were treated with apocynin (30 and 100 mg/kg per day, intragastrically) for 4 weeks. Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer. Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively. Streptozotocin injection reduced pain threshold in analgesimeter, but not in aesthesiometer. Apocynin treatment increased pain threshold dose-dependently. Western blot analysis showed an increase in catalase and NOX-p47phox protein expression in the spinal cord. However, protein expressions of neuronal and inducible nitric oxide synthase (nNOS, iNOS), superoxide dismutase, glutathion peroxidase, nitrotyrosine, tumor necrosis factor-α, interleukin-6, interleukin-1β, aldose reductase, cyclooxygenase-2 or MAC-1 (marker for increased microgliosis) in the spinal cord remained unchanged. Western blot analysis results also demonstrated that apocynin decreased NOX-p47phox expression at both doses and catalase expression at 100 mg/kg per day. Histochemistry of diabetic sciatic nerve revealed marked degeneration. nNOS and iNOS immunoreactivities were increased, while S-100 immunoreactivity (Schwann cell marker) was decreased in sciatic nerve. Apocynin treatment reversed these changes dose-dependently. In conclusion, decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss. Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats. |
format | Online Article Text |
id | pubmed-6126136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-61261362018-09-12 Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats Olukman, Murat Önal, Aytül Çelenk, Fatma Gül Uyanıkgil, Yiğit Çavuşoğlu, Türker Düzenli, Neslihan Ülker, Sibel Neural Regen Res Research Article Increased reactive oxygen species by the activation of NADPH oxidase (NOX) contributes to the development of diabetic complications. Apocynin, a NOX inhibitor, increases sciatic nerve conductance and blood flow in diabetic rats. We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level. Rat models of streptozotocin-induced diabetes were treated with apocynin (30 and 100 mg/kg per day, intragastrically) for 4 weeks. Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer. Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively. Streptozotocin injection reduced pain threshold in analgesimeter, but not in aesthesiometer. Apocynin treatment increased pain threshold dose-dependently. Western blot analysis showed an increase in catalase and NOX-p47phox protein expression in the spinal cord. However, protein expressions of neuronal and inducible nitric oxide synthase (nNOS, iNOS), superoxide dismutase, glutathion peroxidase, nitrotyrosine, tumor necrosis factor-α, interleukin-6, interleukin-1β, aldose reductase, cyclooxygenase-2 or MAC-1 (marker for increased microgliosis) in the spinal cord remained unchanged. Western blot analysis results also demonstrated that apocynin decreased NOX-p47phox expression at both doses and catalase expression at 100 mg/kg per day. Histochemistry of diabetic sciatic nerve revealed marked degeneration. nNOS and iNOS immunoreactivities were increased, while S-100 immunoreactivity (Schwann cell marker) was decreased in sciatic nerve. Apocynin treatment reversed these changes dose-dependently. In conclusion, decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss. Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats. Medknow Publications & Media Pvt Ltd 2018-09 /pmc/articles/PMC6126136/ /pubmed/30127129 http://dx.doi.org/10.4103/1673-5374.232530 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Research Article Olukman, Murat Önal, Aytül Çelenk, Fatma Gül Uyanıkgil, Yiğit Çavuşoğlu, Türker Düzenli, Neslihan Ülker, Sibel Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats |
title | Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats |
title_full | Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats |
title_fullStr | Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats |
title_full_unstemmed | Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats |
title_short | Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats |
title_sort | treatment with nadph oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126136/ https://www.ncbi.nlm.nih.gov/pubmed/30127129 http://dx.doi.org/10.4103/1673-5374.232530 |
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