Gentamicin-induced hearing loss: A retrospective study using the Food and Drug Administration Adverse Event Reporting System and a toxicological study using drug−gene network analysis

The objectives of the study were to evaluate the relationship between gentamicin (GEN) and hearing loss using the Food and Drug Administration Adverse Event Reporting system (FAERS) database and elucidate the potential toxicological mechanism of GEN-induced hearing loss through a drug–gene network a...

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Main Authors: Mizuki Tanaka, Kiyoka Matsumoto, Riko Satake, Yu Yoshida, Misaki Inoue, Shiori Hasegawa, Takaaki Suzuki, Mari Iwata, Kazuhiro Iguchi, Mitsuhiro Nakamura
Format: Article
Language:English
Published: Elsevier 2021-07-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844021015322
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spelling doaj-c4686bd9913b48b585acfabc6df06b952021-08-02T04:57:18ZengElsevierHeliyon2405-84402021-07-0177e07429Gentamicin-induced hearing loss: A retrospective study using the Food and Drug Administration Adverse Event Reporting System and a toxicological study using drug−gene network analysisMizuki Tanaka0Kiyoka Matsumoto1Riko Satake2Yu Yoshida3Misaki Inoue4Shiori Hasegawa5Takaaki Suzuki6Mari Iwata7Kazuhiro Iguchi8Mitsuhiro Nakamura9Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, Japan; Department of Pharmacy, Kobe City Medical Center General Hospital, 2-1-1 Minatojima Minamimachi, Chuo-ku, Kobe, 650-0047, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, Japan; Gifu Prefectural Government, 2-1-1 Yabutaminami, Gifu, 500-8570, JapanKifune Pharmacy, 2-23-2 Hasuike, Yanaizu-cho, Gifu, 501-6103, JapanLaboratory of Community Pharmacy, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1196, Japan; Corresponding author.The objectives of the study were to evaluate the relationship between gentamicin (GEN) and hearing loss using the Food and Drug Administration Adverse Event Reporting system (FAERS) database and elucidate the potential toxicological mechanism of GEN-induced hearing loss through a drug–gene network analysis.Using the preferred terms and standardized queries from the Medical Dictionary for Regulatory Activities, we calculated the reporting odds ratios (RORs). We extracted GEN-associated genes (seed genes) and analyzed drug−gene interactions using the ClueGO plug-in in the Cytoscape software and the DIseAse MOdule Detection (DIAMOnD) algorithm.The lower limit of the 95% confidence interval (CI) of the ROR for aminoglycosides (AG) antibacterials was over 1, and the ROR was 5.5 (5.1–6.0). We retrieved 17 seed genes related to GEN from the PharmGKB and Drug Gene Interaction databases. In total, 1018 human genes interacting with GEN were investigated using ClueGO. Through Molecular Complex Detection (MCODE) analysis, we identified 17 local gene clusters. The nodes and edges of the highest-ranked local gene cluster named “Cluster 1” were 30 and 433, respectively. According to the ClueGO analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Cluster 1 genes were highly enriched in “oxidative phosphorylation.” According to the ClueGO analysis using ClinVar, Cluster 1 genes were highly enriched in “mitochondrial diseases,” “mitochondrial complex I deficiency,” “hereditary hearing loss and deafness,” and “Leigh syndrome.” We identified 60 GEN-associated genes using the DIAMOnD algorithm. Several GEN-associated genes in the DIAMOnD algorithm were highly enriched in “PI3K-Akt signaling pathway,” “Ras signaling pathway,” “focal adhesion,” “MAPK signaling pathway,” “regulation of actin cytoskeleton,” “oxidative phosphorylation,” and “ECM-receptor interaction.”Our analysis demonstrated an association between several AGs and hearing loss using the FAERS database. Drug−gene network analysis demonstrated that GEN may be associated with oxidative phosphorylation-associated genes and integrin genes, which may be associated with hearing loss.http://www.sciencedirect.com/science/article/pii/S2405844021015322Hearing lossGentamicinAminoglycosideFood and Drug Administration Adverse Event Reporting SystemProtein−protein interactionOxidative phosphorylation
collection DOAJ
language English
format Article
sources DOAJ
author Mizuki Tanaka
Kiyoka Matsumoto
Riko Satake
Yu Yoshida
Misaki Inoue
Shiori Hasegawa
Takaaki Suzuki
Mari Iwata
Kazuhiro Iguchi
Mitsuhiro Nakamura
spellingShingle Mizuki Tanaka
Kiyoka Matsumoto
Riko Satake
Yu Yoshida
Misaki Inoue
Shiori Hasegawa
Takaaki Suzuki
Mari Iwata
Kazuhiro Iguchi
Mitsuhiro Nakamura
Gentamicin-induced hearing loss: A retrospective study using the Food and Drug Administration Adverse Event Reporting System and a toxicological study using drug−gene network analysis
Heliyon
Hearing loss
Gentamicin
Aminoglycoside
Food and Drug Administration Adverse Event Reporting System
Protein−protein interaction
Oxidative phosphorylation
author_facet Mizuki Tanaka
Kiyoka Matsumoto
Riko Satake
Yu Yoshida
Misaki Inoue
Shiori Hasegawa
Takaaki Suzuki
Mari Iwata
Kazuhiro Iguchi
Mitsuhiro Nakamura
author_sort Mizuki Tanaka
title Gentamicin-induced hearing loss: A retrospective study using the Food and Drug Administration Adverse Event Reporting System and a toxicological study using drug−gene network analysis
title_short Gentamicin-induced hearing loss: A retrospective study using the Food and Drug Administration Adverse Event Reporting System and a toxicological study using drug−gene network analysis
title_full Gentamicin-induced hearing loss: A retrospective study using the Food and Drug Administration Adverse Event Reporting System and a toxicological study using drug−gene network analysis
title_fullStr Gentamicin-induced hearing loss: A retrospective study using the Food and Drug Administration Adverse Event Reporting System and a toxicological study using drug−gene network analysis
title_full_unstemmed Gentamicin-induced hearing loss: A retrospective study using the Food and Drug Administration Adverse Event Reporting System and a toxicological study using drug−gene network analysis
title_sort gentamicin-induced hearing loss: a retrospective study using the food and drug administration adverse event reporting system and a toxicological study using drug−gene network analysis
publisher Elsevier
series Heliyon
issn 2405-8440
publishDate 2021-07-01
description The objectives of the study were to evaluate the relationship between gentamicin (GEN) and hearing loss using the Food and Drug Administration Adverse Event Reporting system (FAERS) database and elucidate the potential toxicological mechanism of GEN-induced hearing loss through a drug–gene network analysis.Using the preferred terms and standardized queries from the Medical Dictionary for Regulatory Activities, we calculated the reporting odds ratios (RORs). We extracted GEN-associated genes (seed genes) and analyzed drug−gene interactions using the ClueGO plug-in in the Cytoscape software and the DIseAse MOdule Detection (DIAMOnD) algorithm.The lower limit of the 95% confidence interval (CI) of the ROR for aminoglycosides (AG) antibacterials was over 1, and the ROR was 5.5 (5.1–6.0). We retrieved 17 seed genes related to GEN from the PharmGKB and Drug Gene Interaction databases. In total, 1018 human genes interacting with GEN were investigated using ClueGO. Through Molecular Complex Detection (MCODE) analysis, we identified 17 local gene clusters. The nodes and edges of the highest-ranked local gene cluster named “Cluster 1” were 30 and 433, respectively. According to the ClueGO analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Cluster 1 genes were highly enriched in “oxidative phosphorylation.” According to the ClueGO analysis using ClinVar, Cluster 1 genes were highly enriched in “mitochondrial diseases,” “mitochondrial complex I deficiency,” “hereditary hearing loss and deafness,” and “Leigh syndrome.” We identified 60 GEN-associated genes using the DIAMOnD algorithm. Several GEN-associated genes in the DIAMOnD algorithm were highly enriched in “PI3K-Akt signaling pathway,” “Ras signaling pathway,” “focal adhesion,” “MAPK signaling pathway,” “regulation of actin cytoskeleton,” “oxidative phosphorylation,” and “ECM-receptor interaction.”Our analysis demonstrated an association between several AGs and hearing loss using the FAERS database. Drug−gene network analysis demonstrated that GEN may be associated with oxidative phosphorylation-associated genes and integrin genes, which may be associated with hearing loss.
topic Hearing loss
Gentamicin
Aminoglycoside
Food and Drug Administration Adverse Event Reporting System
Protein−protein interaction
Oxidative phosphorylation
url http://www.sciencedirect.com/science/article/pii/S2405844021015322
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