Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice

Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform act...

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Autores principales:	Shareen Singh, Thakur Gurjeet Singh, Manjinder Singh, Agnieszka Najda, Renata Nurzyńska-Wierdak, Rafa Almeer, Mohamed Kamel, Mohamed M. Abdel-Daim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	chondroitin sulfate extracellular matrix intracellular ionic concentration caspase-3 pro-inflammatory mediators oxidative stress Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/a12c42581a1844d89e85c1ff8ae6ec68
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spelling	oai:doaj.org-article:a12c42581a1844d89e85c1ff8ae6ec682021-11-25T18:27:08ZAnticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice10.3390/molecules262267731420-3049https://doaj.org/article/a12c42581a1844d89e85c1ff8ae6ec682021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6773https://doaj.org/toc/1420-3049Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (<i>p</i> < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1β, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1β, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.Shareen SinghThakur Gurjeet SinghManjinder SinghAgnieszka NajdaRenata Nurzyńska-WierdakRafa AlmeerMohamed KamelMohamed M. Abdel-DaimMDPI AGarticlechondroitin sulfateextracellular matrixintracellular ionic concentrationcaspase-3pro-inflammatory mediatorsoxidative stressOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6773, p 6773 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chondroitin sulfate extracellular matrix intracellular ionic concentration caspase-3 pro-inflammatory mediators oxidative stress Organic chemistry QD241-441
spellingShingle	chondroitin sulfate extracellular matrix intracellular ionic concentration caspase-3 pro-inflammatory mediators oxidative stress Organic chemistry QD241-441 Shareen Singh Thakur Gurjeet Singh Manjinder Singh Agnieszka Najda Renata Nurzyńska-Wierdak Rafa Almeer Mohamed Kamel Mohamed M. Abdel-Daim Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice
description	Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (<i>p</i> < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1β, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1β, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.
format	article
author	Shareen Singh Thakur Gurjeet Singh Manjinder Singh Agnieszka Najda Renata Nurzyńska-Wierdak Rafa Almeer Mohamed Kamel Mohamed M. Abdel-Daim
author_facet	Shareen Singh Thakur Gurjeet Singh Manjinder Singh Agnieszka Najda Renata Nurzyńska-Wierdak Rafa Almeer Mohamed Kamel Mohamed M. Abdel-Daim
author_sort	Shareen Singh
title	Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice
title_short	Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice
title_full	Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice
title_fullStr	Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice
title_full_unstemmed	Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice
title_sort	anticonvulsive effects of chondroitin sulfate on pilocarpine and pentylenetetrazole induced epileptogenesis in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a12c42581a1844d89e85c1ff8ae6ec68
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Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice

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