Possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in rats

Abstract Erythropoietin is a renal cytokine involved in regulating hematopoiesis. Current evidence indicates that erythropoietin exerts pleiotropic effects in animal models. However, its role in painful diabetic neuropathy, as well as the possible action mechanisms are not yet established. Therefore...

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Main Authors: SAMUEL SUAREZ-MENDEZ, DEYSI Y. BERMÚDEZ-OCAÑA
Format: Article
Language:English
Published: Academia Brasileira de Ciências 2025-02-01
Series:Anais da Academia Brasileira de Ciências
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Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652025000100604&lng=en&tlng=en
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author SAMUEL SUAREZ-MENDEZ
DEYSI Y. BERMÚDEZ-OCAÑA
author_facet SAMUEL SUAREZ-MENDEZ
DEYSI Y. BERMÚDEZ-OCAÑA
author_sort SAMUEL SUAREZ-MENDEZ
collection DOAJ
description Abstract Erythropoietin is a renal cytokine involved in regulating hematopoiesis. Current evidence indicates that erythropoietin exerts pleiotropic effects in animal models. However, its role in painful diabetic neuropathy, as well as the possible action mechanisms are not yet established. Therefore, this was the purpose of our study. Rats were injected with streptozotocin to produce hyperglycemia. The mechanical allodynia was measured by the up-down method using the von Frey filaments in diabetic rats. To determine the action mechanisms of erythropoietin, levels of NF-κB in serum were measured with ELISA and was used L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride, non-selective nitric oxide synthase inhibitor; 0.1-1 mg/kg, i.p.), glibenclamide (ATP-sensitive K+ channels blocker; 1-10 mg/kg, i.p.), methiothepin (non-selective 5-HT receptor antagonist; 0.01-0.1 mg/kg, i.p.) and naloxone (non-selective opioid receptor antagonist; 1 mg/kg). Intraperitoneal administration of erythropoietin (500-4000 UI/kg) prevented allodynia in diabetic rats. Additionally, erythropoietin significantly decreased serum levels of NF-κB during the evaluation of tactile allodynia and L-NAME, glibenclamide and methiothepin, but not naloxone, reverted erythropoietin-induced antiallodynia. These data suggest erythropoietin effect on painful diabetic neuropathy are mediated at least in part, via deactivation of NF-κB, activation of nitric oxide-ATP-sensitive K+ channel pathway as well as the activation of 5-HT receptors.
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spelling doaj-art-86d9c4e41d62454398c39c8bda15285f2025-02-11T07:42:43ZengAcademia Brasileira de CiênciasAnais da Academia Brasileira de Ciências1678-26902025-02-0197110.1590/0001-3765202520230569Possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in ratsSAMUEL SUAREZ-MENDEZhttps://orcid.org/0000-0002-4295-7033DEYSI Y. BERMÚDEZ-OCAÑAhttps://orcid.org/0000-0002-9750-7670Abstract Erythropoietin is a renal cytokine involved in regulating hematopoiesis. Current evidence indicates that erythropoietin exerts pleiotropic effects in animal models. However, its role in painful diabetic neuropathy, as well as the possible action mechanisms are not yet established. Therefore, this was the purpose of our study. Rats were injected with streptozotocin to produce hyperglycemia. The mechanical allodynia was measured by the up-down method using the von Frey filaments in diabetic rats. To determine the action mechanisms of erythropoietin, levels of NF-κB in serum were measured with ELISA and was used L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride, non-selective nitric oxide synthase inhibitor; 0.1-1 mg/kg, i.p.), glibenclamide (ATP-sensitive K+ channels blocker; 1-10 mg/kg, i.p.), methiothepin (non-selective 5-HT receptor antagonist; 0.01-0.1 mg/kg, i.p.) and naloxone (non-selective opioid receptor antagonist; 1 mg/kg). Intraperitoneal administration of erythropoietin (500-4000 UI/kg) prevented allodynia in diabetic rats. Additionally, erythropoietin significantly decreased serum levels of NF-κB during the evaluation of tactile allodynia and L-NAME, glibenclamide and methiothepin, but not naloxone, reverted erythropoietin-induced antiallodynia. These data suggest erythropoietin effect on painful diabetic neuropathy are mediated at least in part, via deactivation of NF-κB, activation of nitric oxide-ATP-sensitive K+ channel pathway as well as the activation of 5-HT receptors.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652025000100604&lng=en&tlng=enErythropoietinNF-κBNitric oxidePainful diabetic neuropathyPotassium channelsSerotoninergic receptor
spellingShingle SAMUEL SUAREZ-MENDEZ
DEYSI Y. BERMÚDEZ-OCAÑA
Possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in rats
Anais da Academia Brasileira de Ciências
Erythropoietin
NF-κB
Nitric oxide
Painful diabetic neuropathy
Potassium channels
Serotoninergic receptor
title Possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in rats
title_full Possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in rats
title_fullStr Possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in rats
title_full_unstemmed Possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in rats
title_short Possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in rats
title_sort possible erythropoietin pharmacotherapeutic targets on painful diabetic neuropathy in rats
topic Erythropoietin
NF-κB
Nitric oxide
Painful diabetic neuropathy
Potassium channels
Serotoninergic receptor
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652025000100604&lng=en&tlng=en
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