Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats

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dc.contributor.authorOlukman, Murat
dc.contributor.authorOnal, Aytul
dc.contributor.authorCelenk, Fatma Gul
dc.contributor.authorUyanikgil, Yigit
dc.contributor.authorCavusoglu, Turker
dc.contributor.authorDuzenli, Neslihan
dc.contributor.authorUlker, Sibel
dc.date.accessioned2019-10-27T10:03:12Z
dc.date.available2019-10-27T10:03:12Z
dc.date.issued2018
dc.departmentEge Üniversitesien_US
dc.description.abstractIncreased 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-alpha, interleukin-6, interleukin-1 beta, 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.en_US
dc.description.sponsorshipEge UniversityEge University [2010-TIP-076]en_US
dc.description.sponsorshipThis study was supported by the Research Fund of Ege University (Project No. 2010-TIP-076).en_US
dc.identifier.doi10.4103/1673-5374.232530en_US
dc.identifier.endpage1664en_US
dc.identifier.issn1673-5374
dc.identifier.issn1876-7958
dc.identifier.issue9en_US
dc.identifier.pmid30127129en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1657en_US
dc.identifier.urihttps://doi.org/10.4103/1673-5374.232530
dc.identifier.urihttps://hdl.handle.net/11454/30083
dc.identifier.volume13en_US
dc.identifier.wosWOS:000442734700028en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWolters Kluwer Medknow Publicationsen_US
dc.relation.ispartofNeural Regeneration Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectapocyninen_US
dc.subjectdiabetic complicationsen_US
dc.subjectexperimental diabetes mellitusen_US
dc.subjectneuropathic painen_US
dc.subjectNADPH oxidaseen_US
dc.subjectsciatic nerveen_US
dc.subjectspinal corden_US
dc.subjectWestern blottingen_US
dc.subjectperipheral nerve injuryen_US
dc.subjectneural regenerationen_US
dc.titleTreatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in ratsen_US
dc.typeArticleen_US

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