Pterostilbene protects cochlea from ototoxicity in streptozotocin-induced diabetic rats by inhibiting apoptosis

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dc.contributor.authorÖzdaş S.
dc.contributor.authorTaştekin B.
dc.contributor.authorGürgen S.G.
dc.contributor.authorÖzdaş T.
dc.contributor.authorPelit A.
dc.contributor.authorErkan S.O.
dc.contributor.authorTuhanioğlu B.
dc.contributor.authorGülnar B.
dc.contributor.authorGörgülü O.
dc.date.accessioned2024-07-22T08:07:18Z
dc.date.available2024-07-22T08:07:18Z
dc.date.issued2020
dc.description.abstractDiabetes mellitus (DM) causes ototoxicity by inducing oxidative stress, microangiopathy, and apoptosis in the cochlear sensory hair cells. The natural anti-oxidant pterostilbene (PTS) (trans-3,5-dimethoxy-4-hydroxystylbene) has been reported to relieve oxidative stress and apoptosis in DM, but its role in diabetic-induced ototoxicity is unclear. This study aimed to investigate the effects of dose-dependent PTS on the cochlear cells of streptozotocin (STZ)-induced diabetic rats. The study included 30 albino male Wistar rats that were randomized into five groups: non-diabetic control (Control), diabetic control (DM), and diabetic rats treated with intraperitoneal PTS at 10, 20, or 40 mg/kg/day during the four-week experimental period (DM + PTS10, DM + PTS20, and DM + PTS40). Distortion product otoacoustic emission (DPOAE) tests were performed at the beginning and end of the study. At the end of the experimental period, apoptosis in the rat cochlea was investigated using caspase-8, cytochrome-c, and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL). Quantitative real-time polymerase chain reaction was used to assess the mRNA expression levels of the following genes: CASP-3, BCL-associated X protein (BAX), and BCL-2. Body weight, blood glucose, serum insulin, and malondialdehyde (MDA) levels in the rat groups were evaluated. The mean DPOAE amplitude in the DM group was significantly lower than the means of the other groups (0.9–8 kHz; P < 0.001 for all). A dose-dependent increase of the mean DPOAE amplitudes was observed with PTS treatment (P < 0.05 for all). The Caspase-8 and Cytochrome-c protein expressions and the number of TUNEL-positive cells in the hair cells of the Corti organs of the DM rat group were significantly higher than those of the PTS treatment and control groups (DM > DM + PTS10 > DM + PTS20 > DM + PTS40 > Control; P < 0.05 for all). PTS treatment also reduced cell apoptosis in a dose-dependent manner by increasing the mRNA expression of the anti-apoptosis BCL2 gene and by decreasing the mRNA expressions of both the pro-apoptosis BAX gene and its effector CASP-3 and the ratio of BAX/BCL-2 in a dose-dependent manner (P < 0.05 compared to DM for all). PTS treatment significantly improved the metabolic parameters of the diabetic rats, such as body weight, blood glucose, serum insulin, and MDA levels, consistent with our other findings (P < 0.05 compared to DM for all). PTS decreased the cochlear damage caused by diabetes, as confirmed by DPOAE, biochemical, histopathological, immunohistochemical, and molecular findings. This study reports the first in vivo findings to suggest that PTS may be a protective therapeutic agent against diabetes-induced ototoxicity. © 2020 Özdaş et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.identifier.DOI-ID10.1371/journal.pone.0228429
dc.identifier.issn19326203
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13914
dc.language.isoEnglish
dc.publisherPublic Library of Science
dc.rightsAll Open Access; Gold Open Access; Green Open Access
dc.subjectAcoustics
dc.subjectAnimals
dc.subjectbcl-2-Associated X Protein
dc.subjectBody Weight
dc.subjectCaspase 3
dc.subjectCochlea
dc.subjectDiabetes Mellitus, Experimental
dc.subjectDose-Response Relationship, Drug
dc.subjectGene Expression Regulation
dc.subjectMale
dc.subjectOtotoxicity
dc.subjectProtective Agents
dc.subjectRats, Wistar
dc.subjectStilbenes
dc.subjectStreptozocin
dc.subjectcaspase 3
dc.subjectcaspase 8
dc.subjectcytochrome c
dc.subjectDNA nucleotidylexotransferase
dc.subjectglucose
dc.subjectinsulin
dc.subjectmalonaldehyde
dc.subjectmessenger RNA
dc.subjectprotein Bax
dc.subjectprotein bcl 2
dc.subjectpterostilbene
dc.subjectstreptozocin
dc.subjectBax protein, rat
dc.subjectCasp3 protein, rat
dc.subjectprotective agent
dc.subjectpterostilbene
dc.subjectstilbene derivative
dc.subjectstreptozocin
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantiapoptotic activity
dc.subjectapoptosis
dc.subjectArticle
dc.subjectBAX gene
dc.subjectBCL2 gene
dc.subjectbody weight
dc.subjectCASP 3 gene
dc.subjectcell protection
dc.subjectcochlear hair cell
dc.subjectcontrolled study
dc.subjectCorti organ
dc.subjectdiabetic complication
dc.subjectdistortion product otoacoustic emission
dc.subjectgene expression
dc.subjectglucose blood level
dc.subjecthistopathology
dc.subjectimmunohistochemistry
dc.subjectin vivo study
dc.subjectinsulin blood level
dc.subjectmale
dc.subjectnonhuman
dc.subjectototoxicity
dc.subjectprotein expression
dc.subjectrat
dc.subjectreal time polymerase chain reaction
dc.subjectstreptozotocin-induced diabetes mellitus
dc.subjectTUNEL assay
dc.subjectWistar rat
dc.subjectacoustics
dc.subjectanimal
dc.subjectcochlea
dc.subjectcomplication
dc.subjectdose response
dc.subjectdrug effect
dc.subjectexperimental diabetes mellitus
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectototoxicity
dc.subjectpathology
dc.titlePterostilbene protects cochlea from ototoxicity in streptozotocin-induced diabetic rats by inhibiting apoptosis
dc.typeArticle

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