title: Galangin prevents aminoglycoside-induced ototoxicity by decreasing mitochondrial production of reactive oxygen species in mouse cochlear cultures.
abstract: Amikacin is a semi-synthetic aminoglycoside widely used to treat infections caused by gentamicin-resistant gram-negative organisms and nontuberculous mycobacteria. However, the use of this agent often results in ototoxicity due to the overproduction of reactive oxygen species (ROS). Galangin, a natural flavonoid, has been shown to play a protective role against mitochondrial dysfunction by reducing mitochondrial ROS production. In this study, the effect of galangin on amikacin-induced ototoxicity was examined using cultures of cochlear explants. Immunofluorescent staining showed that treatment of inner hair cells (IHCs) and outer hair cells (OHCs) with galangin significantly decreased damage induced by amikacin. Moreover, pretreatment with galangin resulted in decreased amikacin-provoked increase in ROS production in both types of hair cells by MitoSOX-red staining. Attenuation of apoptotic cell death was assessed immunohistochemically using active caspase-3 antibody and with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, compared to explants exposed to amikacin alone (P<0.05). These results indicate that galangin protects hair cells in the organ of Corti from amikacin-induced toxicity by reducing the production of mitochondrial ROS. The results of this study suggest that galangin can potentially be used as an antioxidant and antiapoptotic agent to prevent hearing loss caused by aminoglycoside induced-oxidative stress.
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Ye-Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Min-A
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Daegu, Republic of Korea; Division of Life Sciences, Korea Polar Research Institute (KOPRI), Incheon, Republic of Korea.
authors.forename: Se-Kyung
authors.initials: SK
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Research Institute of Aging and Metabolism, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Daegu, Republic of Korea. Electronic address: kimuk@knu.ac.kr.
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: kylee@knu.ac.kr.
authors.forename: Kyu-Yup
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000617:Aminoglycosides; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D006311:Hearing Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D009925:Organ of Corti / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000617:Aminoglycosides; D000975:Antioxidants; D005419:Flavonoids; D017382:Reactive Oxygen Species; C037032:galangin; D053148:Caspase 3
keywords: Amikacin; Antioxidant; Cochlear explants; Galangin; Ototoxicity