Shaafah Namulodi, Ibrahim Ethem Torun, Fahri Bayiroglu, Mehmet Salih Kaya, Erkan Kilinc
{"title":"Adropin可能通过降低NF-κB/IkB-α信号通路的激活,改善戊四唑诱导的大鼠癫痫发作模型中的行为性癫痫发作以及相关的神经炎症、氧化应激和神经损伤。","authors":"Shaafah Namulodi, Ibrahim Ethem Torun, Fahri Bayiroglu, Mehmet Salih Kaya, Erkan Kilinc","doi":"10.1007/s11011-025-01654-2","DOIUrl":null,"url":null,"abstract":"<p><p>This study aimed to investigate the effects of adropin on seizure activity, neuroinflammation, oxidative stress, and cognitive function in a rat model of pentylenetetrazole (PTZ)-induced seizure. Male Wistar rats were randomly assigned to six groups (n = 7/each group), as follows: control, PTZ, adropin (2 µg/kg or 10 µg/kg) + PTZ, L-NAME + adropin + PTZ, and valproic acid + PTZ groups. Anticonvulsant medicine valproic acid was administered as positive control. Non-selective nitric oxide synthase inhibitor L-NAME was administered together with adropin to elucidate whether adropin exerts its possible effects through the nitric oxide pathway. Behavioral epileptic seizures, biochemical markers of neuroinflammation and relevant pathway, oxidative stress, cognitive function and neural survival/damage were assessed. Adropin (10 µg/kg) reduced PTZ-induced seizure severity and duration, and mitigated cortical and hippocampal pro-inflammatory (IL-1β, IL-6, TNF-α and related transcription factors pNF-κB-p65 and pIκBα), oxidant (MDA) and neural damage (GFAP) markers while elevating anti-inflammatory (IL-10), antioxidant (SOD) and neural survival (BDNF) markers. Combining adropin and L-NAME also exhibited similar effects to adropin alone. In other words, blocking systemic nitric oxide production did not alter the effects of adropin. However, adropin did not significantly improve cognitive performance in the passive avoidance test. Valproic acid, as a positive control, reversed the PTZ-induced effects. These findings suggest that adropin exhibits anticonvulsant, anti-inflammatory, antioxidant and neuroprotective properties in PTZ-induced seizure model potentially through modulation of NF-κB/IkB-α signalling. Therefore, adropin may be a multi-faceted and promising agent in the prevention and management of epileptic seizures in the future.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"222"},"PeriodicalIF":3.5000,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166028/pdf/","citationCount":"0","resultStr":"{\"title\":\"Adropin ameliorates behavioral seizures and the relevant neuroinflammation, oxidative stress, and neural damage in a rat model of pentylenetetrazole-induced seizure potentially by reducing the activation of NF-κB/IkB-α signaling pathway.\",\"authors\":\"Shaafah Namulodi, Ibrahim Ethem Torun, Fahri Bayiroglu, Mehmet Salih Kaya, Erkan Kilinc\",\"doi\":\"10.1007/s11011-025-01654-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study aimed to investigate the effects of adropin on seizure activity, neuroinflammation, oxidative stress, and cognitive function in a rat model of pentylenetetrazole (PTZ)-induced seizure. Male Wistar rats were randomly assigned to six groups (n = 7/each group), as follows: control, PTZ, adropin (2 µg/kg or 10 µg/kg) + PTZ, L-NAME + adropin + PTZ, and valproic acid + PTZ groups. Anticonvulsant medicine valproic acid was administered as positive control. Non-selective nitric oxide synthase inhibitor L-NAME was administered together with adropin to elucidate whether adropin exerts its possible effects through the nitric oxide pathway. Behavioral epileptic seizures, biochemical markers of neuroinflammation and relevant pathway, oxidative stress, cognitive function and neural survival/damage were assessed. Adropin (10 µg/kg) reduced PTZ-induced seizure severity and duration, and mitigated cortical and hippocampal pro-inflammatory (IL-1β, IL-6, TNF-α and related transcription factors pNF-κB-p65 and pIκBα), oxidant (MDA) and neural damage (GFAP) markers while elevating anti-inflammatory (IL-10), antioxidant (SOD) and neural survival (BDNF) markers. Combining adropin and L-NAME also exhibited similar effects to adropin alone. In other words, blocking systemic nitric oxide production did not alter the effects of adropin. However, adropin did not significantly improve cognitive performance in the passive avoidance test. Valproic acid, as a positive control, reversed the PTZ-induced effects. These findings suggest that adropin exhibits anticonvulsant, anti-inflammatory, antioxidant and neuroprotective properties in PTZ-induced seizure model potentially through modulation of NF-κB/IkB-α signalling. Therefore, adropin may be a multi-faceted and promising agent in the prevention and management of epileptic seizures in the future.</p>\",\"PeriodicalId\":18685,\"journal\":{\"name\":\"Metabolic brain disease\",\"volume\":\"40 5\",\"pages\":\"222\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-06-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166028/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Metabolic brain disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11011-025-01654-2\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolic brain disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11011-025-01654-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Adropin ameliorates behavioral seizures and the relevant neuroinflammation, oxidative stress, and neural damage in a rat model of pentylenetetrazole-induced seizure potentially by reducing the activation of NF-κB/IkB-α signaling pathway.
This study aimed to investigate the effects of adropin on seizure activity, neuroinflammation, oxidative stress, and cognitive function in a rat model of pentylenetetrazole (PTZ)-induced seizure. Male Wistar rats were randomly assigned to six groups (n = 7/each group), as follows: control, PTZ, adropin (2 µg/kg or 10 µg/kg) + PTZ, L-NAME + adropin + PTZ, and valproic acid + PTZ groups. Anticonvulsant medicine valproic acid was administered as positive control. Non-selective nitric oxide synthase inhibitor L-NAME was administered together with adropin to elucidate whether adropin exerts its possible effects through the nitric oxide pathway. Behavioral epileptic seizures, biochemical markers of neuroinflammation and relevant pathway, oxidative stress, cognitive function and neural survival/damage were assessed. Adropin (10 µg/kg) reduced PTZ-induced seizure severity and duration, and mitigated cortical and hippocampal pro-inflammatory (IL-1β, IL-6, TNF-α and related transcription factors pNF-κB-p65 and pIκBα), oxidant (MDA) and neural damage (GFAP) markers while elevating anti-inflammatory (IL-10), antioxidant (SOD) and neural survival (BDNF) markers. Combining adropin and L-NAME also exhibited similar effects to adropin alone. In other words, blocking systemic nitric oxide production did not alter the effects of adropin. However, adropin did not significantly improve cognitive performance in the passive avoidance test. Valproic acid, as a positive control, reversed the PTZ-induced effects. These findings suggest that adropin exhibits anticonvulsant, anti-inflammatory, antioxidant and neuroprotective properties in PTZ-induced seizure model potentially through modulation of NF-κB/IkB-α signalling. Therefore, adropin may be a multi-faceted and promising agent in the prevention and management of epileptic seizures in the future.
期刊介绍:
Metabolic Brain Disease serves as a forum for the publication of outstanding basic and clinical papers on all metabolic brain disease, including both human and animal studies. The journal publishes papers on the fundamental pathogenesis of these disorders and on related experimental and clinical techniques and methodologies. Metabolic Brain Disease is directed to physicians, neuroscientists, internists, psychiatrists, neurologists, pathologists, and others involved in the research and treatment of a broad range of metabolic brain disorders.