Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease

Pentoxifylline (PTX) is a phosphodiesterase inhibitor with anti-TNF-alpha activity, associated with its anti-inflammatory action. Considering Parkinson’s disease (PD) as a neuroinflammatory disorder, the objectives were to evaluate PTX neuroprotective properties, in a model of PD. Male Wistar rats,...

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Main Authors: Kelly Rose Tavares Neves, Hélio Vitoriano Nobre, Luzia Kalyne A. M. Leal, Geanne Matos de Andrade, Gerly Anne de Castro Brito, Glauce Socorro de Barros Viana
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Parkinson's Disease
Online Access:http://dx.doi.org/10.1155/2015/108179
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author Kelly Rose Tavares Neves
Hélio Vitoriano Nobre
Luzia Kalyne A. M. Leal
Geanne Matos de Andrade
Gerly Anne de Castro Brito
Glauce Socorro de Barros Viana
author_facet Kelly Rose Tavares Neves
Hélio Vitoriano Nobre
Luzia Kalyne A. M. Leal
Geanne Matos de Andrade
Gerly Anne de Castro Brito
Glauce Socorro de Barros Viana
author_sort Kelly Rose Tavares Neves
collection DOAJ
description Pentoxifylline (PTX) is a phosphodiesterase inhibitor with anti-TNF-alpha activity, associated with its anti-inflammatory action. Considering Parkinson’s disease (PD) as a neuroinflammatory disorder, the objectives were to evaluate PTX neuroprotective properties, in a model of PD. Male Wistar rats, divided into sham-operated (SO), untreated 6-OHDA, and 6-OHDA treated with PTX (10, 25, and 50 mg/kg) groups, received a unilateral 6-OHDA injection, except the SO group administered with saline. Treatments started 24 h after surgery and continued for 15 days when the animals were submitted to apomorphine-induced rotations, open field, and forced swimming tests. At the next day, they were euthanized and their striata processed for neurochemical (DA and DOPAC determinations), histological, and immunohistochemical (Fluoro-Jade, TH, DAT, OX-42, TNF-alpha, COX-2, and iNOS) studies. PTX reversed the behavioral changes observed in the untreated 6-OHDA animals. Furthermore, PTX partially reversed the decrease in DA contents and improved neuronal viability. In addition, decreases in immunostaining for TH and dopamine transporter (DAT) were reversed. The untreated 6-OHDA group showed intense OX-42, TNF-alpha, COX-2, and iNOS immunoreactivities, which were attenuated by PTX. In conclusion, we demonstrated a neuroprotective effect of PTX, possibly related to its anti-inflammatory and antioxidant actions, indicating its potential as an adjunct treatment for PD.
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spelling doaj-art-96202b2f544c4ffeb994b6f1f9d0f1922025-02-03T06:13:25ZengWileyParkinson's Disease2090-80832042-00802015-01-01201510.1155/2015/108179108179Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s DiseaseKelly Rose Tavares Neves0Hélio Vitoriano Nobre1Luzia Kalyne A. M. Leal2Geanne Matos de Andrade3Gerly Anne de Castro Brito4Glauce Socorro de Barros Viana5Faculty of Medicine of the Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60430-270 Fortaleza, CE, BrazilFaculty of Medicine of the Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60430-270 Fortaleza, CE, BrazilFaculty of Medicine of the Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60430-270 Fortaleza, CE, BrazilFaculty of Medicine of the Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60430-270 Fortaleza, CE, BrazilFaculty of Medicine of the Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60430-270 Fortaleza, CE, BrazilFaculty of Medicine of the Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60430-270 Fortaleza, CE, BrazilPentoxifylline (PTX) is a phosphodiesterase inhibitor with anti-TNF-alpha activity, associated with its anti-inflammatory action. Considering Parkinson’s disease (PD) as a neuroinflammatory disorder, the objectives were to evaluate PTX neuroprotective properties, in a model of PD. Male Wistar rats, divided into sham-operated (SO), untreated 6-OHDA, and 6-OHDA treated with PTX (10, 25, and 50 mg/kg) groups, received a unilateral 6-OHDA injection, except the SO group administered with saline. Treatments started 24 h after surgery and continued for 15 days when the animals were submitted to apomorphine-induced rotations, open field, and forced swimming tests. At the next day, they were euthanized and their striata processed for neurochemical (DA and DOPAC determinations), histological, and immunohistochemical (Fluoro-Jade, TH, DAT, OX-42, TNF-alpha, COX-2, and iNOS) studies. PTX reversed the behavioral changes observed in the untreated 6-OHDA animals. Furthermore, PTX partially reversed the decrease in DA contents and improved neuronal viability. In addition, decreases in immunostaining for TH and dopamine transporter (DAT) were reversed. The untreated 6-OHDA group showed intense OX-42, TNF-alpha, COX-2, and iNOS immunoreactivities, which were attenuated by PTX. In conclusion, we demonstrated a neuroprotective effect of PTX, possibly related to its anti-inflammatory and antioxidant actions, indicating its potential as an adjunct treatment for PD.http://dx.doi.org/10.1155/2015/108179
spellingShingle Kelly Rose Tavares Neves
Hélio Vitoriano Nobre
Luzia Kalyne A. M. Leal
Geanne Matos de Andrade
Gerly Anne de Castro Brito
Glauce Socorro de Barros Viana
Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease
Parkinson's Disease
title Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease
title_full Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease
title_fullStr Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease
title_full_unstemmed Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease
title_short Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease
title_sort pentoxifylline neuroprotective effects are possibly related to its anti inflammatory and tnf alpha inhibitory properties in the 6 ohda model of parkinson s disease
url http://dx.doi.org/10.1155/2015/108179
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