The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced Neurotoxicity

SUMMARY: The aim of this study was to determine the relationship of autophagy-enhancing rapamycin (RAPA) and autophagy- inhibitor 3-methyladenine (3-MA) with Nitric oxide synthases (NOS) in Cisplatin (CIS)-induced neurotoxicity in rats. Rats were divided into 4 groups (n=10): Control was applied sal...

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Autores principales:	Kaymak,Emin, Karabulut,Derya, Ozturk,Emel, Akin,Ali Tugrul, Yakan,Birkan
Lenguaje:	English
Publicado:	Sociedad Chilena de Anatomía 2021
Materias:	Antioxidant Cisplatin Rapamycin 3-Methyladenine Nitric oxide
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000200659
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spelling	oai:scielo:S0717-950220210002006592021-04-22The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced NeurotoxicityKaymak,EminKarabulut,DeryaOzturk,EmelAkin,Ali TugrulYakan,Birkan Antioxidant Cisplatin Rapamycin 3-Methyladenine Nitric oxide SUMMARY: The aim of this study was to determine the relationship of autophagy-enhancing rapamycin (RAPA) and autophagy- inhibitor 3-methyladenine (3-MA) with Nitric oxide synthases (NOS) in Cisplatin (CIS)-induced neurotoxicity in rats. Rats were divided into 4 groups (n=10): Control was applied saline, CIS (a single dose of 8mg/kg intraperitoneal (i.p.) on 7th day of experiment), RAPA+CIS (2 mg/kg/i.p. RAPA per day and 8 mg/kg/i.p. CIS on 7th day), 3-MA+CIS (15 mg/kg/i.p. 3-MA per day and 8 mg/kg/i.p. CIS on 7th day). Rats were sacrificed under anesthesia. Brain tissues were evaluated histopathologically. eNOS, Inos, nNOS and MAP 2 immunostaining were performed to determine the expression levels of these proteins among groups. Superoxide dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA) and Interleukin IL-6 levels in brain tissue and serum nitric oxide (NO) level were measured by ELISA assay. In histopathological evaluation, neurodegeneration was seen in the CIS group. There was an increase in eNOS, iNOS and nNOS immunostaining in CIS group. While MAP2 immunostaining of the CIS group decreased. There was a decrease in SOD and CAT levels of brain tissue in CIS group. However, there was an increase in MDA, IL-6 and NO levels of brain tissue in CIS group. We found that antioxidant capacity increase while, inflammation and nitric oxide levels decreased in the RAPA-treated group. 3-MA does not have a significant effect. We suggest that CIS-induced neurotoxicity is more effective than Rapa 3-MA and may also be linked to NOS enzymes.info:eu-repo/semantics/openAccessSociedad Chilena de AnatomíaInternational Journal of Morphology v.39 n.2 20212021-04-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000200659en10.4067/S0717-95022021000200659
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Antioxidant Cisplatin Rapamycin 3-Methyladenine Nitric oxide
spellingShingle	Antioxidant Cisplatin Rapamycin 3-Methyladenine Nitric oxide Kaymak,Emin Karabulut,Derya Ozturk,Emel Akin,Ali Tugrul Yakan,Birkan The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced Neurotoxicity
description	SUMMARY: The aim of this study was to determine the relationship of autophagy-enhancing rapamycin (RAPA) and autophagy- inhibitor 3-methyladenine (3-MA) with Nitric oxide synthases (NOS) in Cisplatin (CIS)-induced neurotoxicity in rats. Rats were divided into 4 groups (n=10): Control was applied saline, CIS (a single dose of 8mg/kg intraperitoneal (i.p.) on 7th day of experiment), RAPA+CIS (2 mg/kg/i.p. RAPA per day and 8 mg/kg/i.p. CIS on 7th day), 3-MA+CIS (15 mg/kg/i.p. 3-MA per day and 8 mg/kg/i.p. CIS on 7th day). Rats were sacrificed under anesthesia. Brain tissues were evaluated histopathologically. eNOS, Inos, nNOS and MAP 2 immunostaining were performed to determine the expression levels of these proteins among groups. Superoxide dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA) and Interleukin IL-6 levels in brain tissue and serum nitric oxide (NO) level were measured by ELISA assay. In histopathological evaluation, neurodegeneration was seen in the CIS group. There was an increase in eNOS, iNOS and nNOS immunostaining in CIS group. While MAP2 immunostaining of the CIS group decreased. There was a decrease in SOD and CAT levels of brain tissue in CIS group. However, there was an increase in MDA, IL-6 and NO levels of brain tissue in CIS group. We found that antioxidant capacity increase while, inflammation and nitric oxide levels decreased in the RAPA-treated group. 3-MA does not have a significant effect. We suggest that CIS-induced neurotoxicity is more effective than Rapa 3-MA and may also be linked to NOS enzymes.
author	Kaymak,Emin Karabulut,Derya Ozturk,Emel Akin,Ali Tugrul Yakan,Birkan
author_facet	Kaymak,Emin Karabulut,Derya Ozturk,Emel Akin,Ali Tugrul Yakan,Birkan
author_sort	Kaymak,Emin
title	The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced Neurotoxicity
title_short	The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced Neurotoxicity
title_full	The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced Neurotoxicity
title_fullStr	The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced Neurotoxicity
title_full_unstemmed	The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced Neurotoxicity
title_sort	effects of rapamycin and 3-methyladenine on nitric oxide synthase enzymes in cisplatin-induced neurotoxicity
publisher	Sociedad Chilena de Anatomía
publishDate	2021
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000200659
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The Effects of Rapamycin and 3-Methyladenine on Nitric Oxide Synthase Enzymes in Cisplatin-Induced Neurotoxicity

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