Effects of pentoxifylline and its metabolites on platelet aggregation in whole blood from healthy humans

Magnusson, Marie; Gunnarsson, Mikael; Berntorp, Erik; Björkman, Sven; Höglund, Peter

doi:10.1016/j.ejphar.2007.11.054

Cited by 30 publications

(30 citation statements)

References 14 publications

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“…Pentoxifylline (PTX) is a methylxanthine derivative and a nonspecific type 4 phosphodiesterase inhibitor. It is used clinically to treat patients with peripheral vascular diseases [17] . Its pharmacological mechanisms are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of tubulointerstitial fibrosis by pentoxifylline is associated with improvement of vascular endothelial growth factor expression

2008

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Aim: Recent information indicates that pentoxifylline (PTX) has the ability to suppress inflammation and profibrotic cell proliferation. In this study, we investigated the effect of PTX on tubulointerstitial fibrosis and the expression of vascular endothelial growth factor (VEGF) in a rat model of obstructive nephropathy. Methods: Wistar rats with left ureteral ligation were divided into control and PTX-treated groups. The histopathologic degree of tubulointerstitial fibrosis was scored with PAS and Masson-stained sections. The protein and mRNA for vascular endothelial growth factor (VEGF) were semiquantitatively measured with immunohistochemistry and RT-PCR. The protein for transforming growth factor β1 (TGFβ1) and hypoxia-induced factor 1 alpha (HIF-1α) was determined by Western blot.

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Section: Introductionmentioning

confidence: 99%

Inhibition of tubulointerstitial fibrosis by pentoxifylline is associated with improvement of vascular endothelial growth factor expression

2008

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“…Ex vivo and in vitro investigations have also demonstrated the antiplatelet properties of this compound (12,(25)(26)(27)(28)(29)(30). However, at difference of the PDE inhibitor cilostazol, to date there are no studies that have assessed the impact of pentoxifylline on platelet function profiles in patients receiving DAPT.…”

Section: Discussionmentioning

confidence: 98%

Impact of Pentoxifylline on Platelet Function Profiles in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel

Ueno¹,

Ferreiro²,

Tomasello³

et al. 2011

JACC: Cardiovascular Interventions

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“…Also, clonidine's anti-allodynic effects were mimicked by apraclondine, which does not cross the blood brain barrier 83 . In addition, the many of the various anti-inflammatory activities of pentoxifylline and lisofylline are linked with their vascular effects 7,62,76,91 , as microvascular function is key to various processes involved in the inflammatory response, including plasma extravasation, platelet aggregration, leukocyte migration, cytokine activation, among others.…”

Section: Discussionmentioning

confidence: 99%

“…For example, clonidine acts at imidazoline receptors as well as α 2A receptors 88 , and pentoxiphylline is a non-specific PDE inhibitor that produces anti-inflammatory effects by interacting with various biological systems. Furthermore, although lisofylline is a phosphatidic acid inhibitor, it is a metabolite of pentoxifylline 62,76 , and shares many of pentoxifylline's PDE inhibitor activities, including inhibition of various cytokines 76 . However, topical administered clonidine is unlikely to have significant effects at brainstem imidazoline receptors, especially at the low concentrations we have used.…”

Section: Discussionmentioning

confidence: 99%

“…However, α 2A receptor agonists, NO donors and PDE inhibitors have been used systemically in patients or preclinical animal models to treat pain associated with angina 13,43,66 , PAD 19,52,82 , CRPS 18,40,63,74 , neuropathic pain 32,53,60 and PDN 16,24,48,84 indicating their usefulness in these syndromes. PA inhibitors have not been used to treat chronic pain, but should be equally or more effective than PDE inhibitors since they have anti-oxidant 7,34 , anticytokine 68,76 , anti-chemotaxic 70,91 , immunosuppressant 15,23 , and mitochondrial protective 12 effects, in addition to the vasodilator 61 , anti-ischemic 90 and anti-platelet aggregation 62 effects they share with PDE inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

Ragavendran

Laferrière

Xiao

et al. 2013

The Journal of Pain

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Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α 2 -adrenergic (α 2A ) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent anti-allodynic effects in rats with chronic post- CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript ischemia pain, and the anti-allodynic dose-response curves of PDE and PA inhibitors were shifted 2.5-10 fold leftward when combined with non-analgesic doses of α 2A receptor agonists or NO donors. Topical combinations also produced significant anti-allodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 h after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α 2A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain.Perspective-This article presents the synergistic anti-allodynic effects of combinations of α 2A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas.

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Effects of pentoxifylline and its metabolites on platelet aggregation in whole blood from healthy humans

Cited by 30 publications

References 14 publications

Inhibition of tubulointerstitial fibrosis by pentoxifylline is associated with improvement of vascular endothelial growth factor expression

Inhibition of tubulointerstitial fibrosis by pentoxifylline is associated with improvement of vascular endothelial growth factor expression

Impact of Pentoxifylline on Platelet Function Profiles in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

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