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dc.contributor.authorÜnal, İsmail
dc.contributor.authorCansız, Derya
dc.contributor.authorBeler, Merih
dc.contributor.authorSezer, Zehra
dc.contributor.authorGüzel, Elif
dc.contributor.authorEmekli Alturfan, Ebru
dc.date.accessioned2023-09-15T06:27:23Z
dc.date.available2023-09-15T06:27:23Z
dc.date.issued2023en_US
dc.identifier.citationÜnal, İ., Cansız, D., Beler, M., Sezer, Z., Güzel, E. ve Emekli Alturfan, E. (2023). Sodium-dependent glucose co-transporter-2 inhibitor empagliflozin exerts neuroprotective effects in rotenone-induced Parkinson's disease model in zebrafish; mechanism involving ketogenesis and autophagy. Brain Research, 1820. https://dx.doi.org/10.1016/j.brainres.2023.148536en_US
dc.identifier.issn0006-8993
dc.identifier.urihttps://dx.doi.org/10.1016/j.brainres.2023.148536
dc.identifier.urihttps://hdl.handle.net/20.500.12511/11437
dc.description.abstractSodium-dependent glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (EMP), is the new class of oral hypoglycemic agent approved as a treatment for Type 2 diabetes. SGLT2 inhibitors may induce ketogenesis through inhibiting the renal reabsorption of glucose. In recent years, positive effects of ketogenic diets on neurodegenerative diseases such as Parkinson's disease (PD) have been reported by improving autophagy. We aimed to evaluate the effects of EMP treatment as a SGLT2 inhibitor that can mimic the effects of ketogenic diet, in rotenone induced PD model in zebrafish focusing on ketogenesis, autophagy, and molecular pathways related with PD progression including oxidative stress and inflammation. Adult zebrafish were exposed to rotenone and EMP for 30 days. Y-Maze task and locomotor analysis were performed. Neurotransmitter levels were determined by liquid chromatography tandem- mass spectrometry (LC-MS/MS). Lipid peroxidation (LPO), nitric oxide (No), alkaline phosphatase, superoxide dismutase, glutathione, glutathione S-transferase (GST), sialic acid, acetylcholinesterase, and the expressions of autophagy, ketogenesis and PD-related genes were determined. Immunohistochemical staining was performed for the microglial marker L-plastin (Lcp1) and tyrosine hydroxylase (Th). EMP treatment improved DOPAC/DA ratio, Y-Maze task, locomotor activity, expressions of Th and Lcp-1, autophagy and inflammation related (mTor, atg5, tnfα, sirt1, il6, tnfα); PD-related (lrrk2, park2, park7, pink1), and ketone metabolism-related genes (slc16a1b, pparag, and pparab), and oxidant-damage in brain in the rotenone group as evidenced by decreased LPO, No, and improved antioxidant molecules. Our results showed benefical effects of EMP as a SGLT2 inhibitor in neurotoxin-induced PD model in zebrafish. We believe our study, will shed light on the mechanism of the effects of SGLT2 inhibitors, ketogenesis and autopahgy in PD.en_US
dc.description.sponsorshipMarmara Universityen_US
dc.language.isoengen_US
dc.publisherElsevier B.V.en_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectAutophagyen_US
dc.subjectEmpagliflozinen_US
dc.subjectKetogenesisen_US
dc.subjectParkinson's Diseaseen_US
dc.subjectSodium-Dependent Glucose Transporteren_US
dc.titleSodium-dependent glucose co-transporter-2 inhibitor empagliflozin exerts neuroprotective effects in rotenone-induced Parkinson's disease model in zebrafish; mechanism involving ketogenesis and autophagyen_US
dc.typearticleen_US
dc.relation.ispartofBrain Researchen_US
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalıen_US
dc.authorid0000-0002-6274-801Xen_US
dc.identifier.volume1820en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1016/j.brainres.2023.148536en_US
dc.institutionauthorCansız, Derya
dc.identifier.wosqualityQ3en_US
dc.identifier.wos001073530200001en_US
dc.identifier.scopus2-s2.0-85170055777en_US
dc.identifier.pmid37591458en_US
dc.identifier.scopusqualityQ2en_US


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