The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes

BACKGROUND: Different organs respond differently to cisplatin (CDDP)-induced toxicity. Oleuropein (OLE) is a natural phenolic antioxidant. The purpose of this study was to determine the potential protective effect of OLE against CDDP-induced ototoxicity by evaluating expression of genes associated w...

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Main Authors: Yüksel Olgun, Zekiye Altun, Merve Tütüncü, Selen Kum Özşengezer, Safiye Aktaş, Enis Alpin Güneri
Format: Article
Language:English
Published: AVES 2024-05-01
Series:Journal of International Advanced Otology
Online Access:https://www.advancedotology.org/en/the-impact-of-oleuropein-on-cisplatin-induced-toxicity-in-cochlear-cells-in-relation-to-the-expression-of-deoxyribonucleic-acid-damage-associated-genes-131917
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author Yüksel Olgun
Zekiye Altun
Merve Tütüncü
Selen Kum Özşengezer
Safiye Aktaş
Enis Alpin Güneri
author_facet Yüksel Olgun
Zekiye Altun
Merve Tütüncü
Selen Kum Özşengezer
Safiye Aktaş
Enis Alpin Güneri
author_sort Yüksel Olgun
collection DOAJ
description BACKGROUND: Different organs respond differently to cisplatin (CDDP)-induced toxicity. Oleuropein (OLE) is a natural phenolic antioxidant. The purpose of this study was to determine the potential protective effect of OLE against CDDP-induced ototoxicity by evaluating expression of genes associated with deoxyribonucleic acid (DNA) damage and repair in cochlear cells. METHODS: House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated using CDDP, OLE, and OLE–CDDP. The water-soluble tetrazolium salt assay was used for monitoring cell viability. Deoxyribonucleic acid damage in cells due to the CDDP, OLE, and combination treatments was determined using a flow-cytometric kit. The change in the expression of 84 genes associated with CCDP, OLE, and OLE–CDDP treatments that induced DNA damage was tested using the reverse transcription polymerase chain reaction array. Changes ≥3-fold were considered significant. RESULTS: House Ear Institute-Organ of Corti 1 cell viability was significantly reduced by CDDP. The OLE–CDDP combination restored the cell viability. Cisplatin increased the H2AX ratio, while OLE–CDDP combination decreased it. Some of the DNA damage-associated genes whose expression was upregulated with CDDP were downregulated with OLE–CDDP, while the expression of genes such as Gadd45g and Rev1 was further downregulated. The expression of DNA repair-related Abl1, Dbd2, Rad52, and Trp53 genes was downregulated with CDDP, whereas their expression was upregulated with OLE–CDDP treatment. CONCLUSION: In cochlear cells, the OLE–CDDP combination downregulated DNA damage-associated gene expression relative to that upregulated mainly by CDDP. The results revealed that OLE has a potential protective effect on CDDP-induced ototoxicity in cochlear cells by altering the expression of DNA damage-related genes.
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spelling doaj-art-79f579dd7272489ea7f9ac127d06eee32025-02-02T23:18:15ZengAVESJournal of International Advanced Otology2148-38172024-05-0120318919510.5152/iao.2024.231288The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated GenesYüksel Olgun0Zekiye Altun1Merve Tütüncü2Selen Kum Özşengezer3Safiye Aktaş4Enis Alpin Güneri5Department of Otorhinolaryngology, Dokuz Eylül University School of Medicine, İzmir, TürkiyeDepartment of Basic Oncology, Dokuz Eylül University Institute of Oncology, İzmir, TürkiyeDepartment of Basic Oncology, Dokuz Eylül University Institute of Oncology, İzmir, TürkiyeDepartment of Basic Oncology, Dokuz Eylül University Institute of Oncology, İzmir, TürkiyeDepartment of Basic Oncology, Dokuz Eylül University Institute of Oncology, İzmir, TürkiyeDepartment of Otorhinolaryngology, Dokuz Eylül University School of Medicine, İzmir, TürkiyeBACKGROUND: Different organs respond differently to cisplatin (CDDP)-induced toxicity. Oleuropein (OLE) is a natural phenolic antioxidant. The purpose of this study was to determine the potential protective effect of OLE against CDDP-induced ototoxicity by evaluating expression of genes associated with deoxyribonucleic acid (DNA) damage and repair in cochlear cells. METHODS: House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated using CDDP, OLE, and OLE–CDDP. The water-soluble tetrazolium salt assay was used for monitoring cell viability. Deoxyribonucleic acid damage in cells due to the CDDP, OLE, and combination treatments was determined using a flow-cytometric kit. The change in the expression of 84 genes associated with CCDP, OLE, and OLE–CDDP treatments that induced DNA damage was tested using the reverse transcription polymerase chain reaction array. Changes ≥3-fold were considered significant. RESULTS: House Ear Institute-Organ of Corti 1 cell viability was significantly reduced by CDDP. The OLE–CDDP combination restored the cell viability. Cisplatin increased the H2AX ratio, while OLE–CDDP combination decreased it. Some of the DNA damage-associated genes whose expression was upregulated with CDDP were downregulated with OLE–CDDP, while the expression of genes such as Gadd45g and Rev1 was further downregulated. The expression of DNA repair-related Abl1, Dbd2, Rad52, and Trp53 genes was downregulated with CDDP, whereas their expression was upregulated with OLE–CDDP treatment. CONCLUSION: In cochlear cells, the OLE–CDDP combination downregulated DNA damage-associated gene expression relative to that upregulated mainly by CDDP. The results revealed that OLE has a potential protective effect on CDDP-induced ototoxicity in cochlear cells by altering the expression of DNA damage-related genes.https://www.advancedotology.org/en/the-impact-of-oleuropein-on-cisplatin-induced-toxicity-in-cochlear-cells-in-relation-to-the-expression-of-deoxyribonucleic-acid-damage-associated-genes-131917
spellingShingle Yüksel Olgun
Zekiye Altun
Merve Tütüncü
Selen Kum Özşengezer
Safiye Aktaş
Enis Alpin Güneri
The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes
Journal of International Advanced Otology
title The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes
title_full The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes
title_fullStr The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes
title_full_unstemmed The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes
title_short The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes
title_sort impact of oleuropein on cisplatin induced toxicity in cochlear cells in relation to the expression of deoxyribonucleic acid damage associated genes
url https://www.advancedotology.org/en/the-impact-of-oleuropein-on-cisplatin-induced-toxicity-in-cochlear-cells-in-relation-to-the-expression-of-deoxyribonucleic-acid-damage-associated-genes-131917
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