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

Kelly Rose Tavares Neves,Glauce Socorro De Barros Viana,Geanne Matos De Andrade,Gerly Anne De Castro Brito,Hélio Vitoriano Nobre,Luzia Kalyne A M Leal

doi:10.1155/2015/108179

Kelly Rose Tavares Neves, Glauce Socorro De Barros Viana + Show 4 more

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https://doi.org/10.1155/2015/108179

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Abstract

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.

Highlights

Pentoxifylline (PTX) is a nonselective phosphodiesterase inhibitor that decreases TNF-alpha gene transcription, affecting directly or indirectly multiple steps in the cytokine/ chemokine pathways and exerting beneficial immunomodulatory effects in inflammatory conditions [1]
[6], we demonstrated that caffeine, a nonselective adenosine A2A antagonist, as PTX, attenuates the striatal dopaminergic loss and decreases proinflammatory cytokines, as TNF-alpha and IL-1 beta, in the Parkinson’s disease (PD) model of 6-OHDA lesion
The results showed almost no contralateral rotation in the SO group, while the untreated 6-OHDA group presented 218.3 ± 33.74 rotations/h

Summary

Introduction

Pentoxifylline (PTX) is a nonselective phosphodiesterase inhibitor that decreases TNF-alpha gene transcription, affecting directly or indirectly multiple steps in the cytokine/ chemokine pathways and exerting beneficial immunomodulatory effects in inflammatory conditions [1]. As TNF-alpha, are involved in the regulation of the central nervous system (CNS) and immune system interactions and are important for the coordination of immune responses throughout the body. In the CNS, cytokines as well as chemokines function as neuromodulators and regulate neurodevelopment, neuroinflammation, and synaptic transmission. PD is a chronic neurodegenerative disease clinically characterized by bradykinesia, hypokinesia, rigidity, resting tremor, and postural instability.

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