Greice Nascimento Pires , Renata Pereira Laurindo , Luiza Dos Santos Heringer , Stefanny Calixto da Silva , Débora Magalhães Portela , Ricardo Cardoso , Ana Carolina de Pádua , Ana Beatriz Miranda De Sá , Saulo Augusto Alves Da Cruz , Sheila Espírito Santo Araújo , Ana Maria Blanco Martinez , Milena Batista Carneiro , Henrique Rocha Mendonça
{"title":"Therapeutic potential of pranlukast against cuprizone-induced inflammatory demyelination and sensory impairment in mice: Comparison with fingolimod","authors":"Greice Nascimento Pires , Renata Pereira Laurindo , Luiza Dos Santos Heringer , Stefanny Calixto da Silva , Débora Magalhães Portela , Ricardo Cardoso , Ana Carolina de Pádua , Ana Beatriz Miranda De Sá , Saulo Augusto Alves Da Cruz , Sheila Espírito Santo Araújo , Ana Maria Blanco Martinez , Milena Batista Carneiro , Henrique Rocha Mendonça","doi":"10.1016/j.neuro.2025.01.004","DOIUrl":null,"url":null,"abstract":"<div><div>Inflammatory demyelination is present in debilitating diseases such as Multiple Sclerosis (MS). Several drugs are available for MS treatment, with fingolimod as a first-line oral option in the United States. However, a cure has yet to be established, and therapeutic failures are common, highlighting the need for continued research into new pharmacological targets. Pranlukast has shown positive effects on myelination in cell cultures and after LPC-induced demyelination in mice, but it is not yet part of the therapeutic arsenal for this disease. This study investigates pranlukast’s effect on demyelination protection in an MS animal model, compared to fingolimod. For this purpose, young adult Swiss mice were treated for five weeks with a 0.2 % cuprizone diet and received daily intraperitoneal injections of pranlukast (0.1 mg/kg), fingolimod (1 mg/kg), or vehicle. Pranlukast treatment, like fingolimod, partially preserved sensory function in the tactile sensitivity test. Both treatments partially preserved myelin basic protein (MBP) levels, but only fingolimod preserved lipids and myelinated fibers in the corpus callosum (CC) at all g-ratio ranges. Cuprizone and Pranlukast groups presented more microglia/macrophages in the CC, but fewer presenting reactive microglia/macrophages and less NOS2 staining in pranlukast-treated when compared to the cuprizone group, while fingolimod treatment prevented the increase in Iba1 in the CC. In summary, this study demonstrated that pranlukast is a good candidate as a novel drug for use in conditions of inflammatory demyelination, such as MS, by restoring function through modulation of the inflammatory environment.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"107 ","pages":"Pages 37-52"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurotoxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161813X25000130","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Inflammatory demyelination is present in debilitating diseases such as Multiple Sclerosis (MS). Several drugs are available for MS treatment, with fingolimod as a first-line oral option in the United States. However, a cure has yet to be established, and therapeutic failures are common, highlighting the need for continued research into new pharmacological targets. Pranlukast has shown positive effects on myelination in cell cultures and after LPC-induced demyelination in mice, but it is not yet part of the therapeutic arsenal for this disease. This study investigates pranlukast’s effect on demyelination protection in an MS animal model, compared to fingolimod. For this purpose, young adult Swiss mice were treated for five weeks with a 0.2 % cuprizone diet and received daily intraperitoneal injections of pranlukast (0.1 mg/kg), fingolimod (1 mg/kg), or vehicle. Pranlukast treatment, like fingolimod, partially preserved sensory function in the tactile sensitivity test. Both treatments partially preserved myelin basic protein (MBP) levels, but only fingolimod preserved lipids and myelinated fibers in the corpus callosum (CC) at all g-ratio ranges. Cuprizone and Pranlukast groups presented more microglia/macrophages in the CC, but fewer presenting reactive microglia/macrophages and less NOS2 staining in pranlukast-treated when compared to the cuprizone group, while fingolimod treatment prevented the increase in Iba1 in the CC. In summary, this study demonstrated that pranlukast is a good candidate as a novel drug for use in conditions of inflammatory demyelination, such as MS, by restoring function through modulation of the inflammatory environment.
期刊介绍:
NeuroToxicology specializes in publishing the best peer-reviewed original research papers dealing with the effects of toxic substances on the nervous system of humans and experimental animals of all ages. The Journal emphasizes papers dealing with the neurotoxic effects of environmentally significant chemical hazards, manufactured drugs and naturally occurring compounds.