Berberine chloride protects cochlear hair cells from aminoglycoside-induced ototoxicity by reducing the accumulation of mitochondrial reactive oxygen species

• Published in: Free radical biology & medicine Vol. 204; pp. 177 - 183
• Main Authors: Kim, Ye-Ri, Baek, Jeong-In, Lee, Kyu-Yup, Kim, Un-Kyung
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2023
• Subjects: Aminoglycoside; Aminoglycosides - metabolism; Aminoglycosides - toxicity; Animals; Anti-Bacterial Agents - adverse effects; Berberine - pharmacology; Berberine chloride; Caspase 3 - genetics; Caspase 3 - metabolism; Chlorides; Hair Cells, Auditory; Hearing loss; Mice; Ototoxicity; Ototoxicity - etiology; Ototoxicity - metabolism; Ototoxicity - prevention & control; Reactive Oxygen Species - metabolism; ROS; Berberine chloride; Aminoglycoside; ROS; Ototoxicity; Hearing loss
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2023.04.017

Aminoglycoside, a medicinal category of antibiotics, are used in treatment of Gram-negative bacterial infections. Although they are the most widely-used antibiotics due to their high efficacy and low cost, several main adverse effects have been reported including nephrotoxicity and ototoxicity. Since drug-induced ototoxicity is one of the major etiological causes of acquired hearing loss, we examined cochlear hair cell damages caused by three aminoglycosides (amikacin, kanamycin, and gentamicin), and investigated protective property of an isoquinoline-type alkaloid, Berberine chloride (BC). Berberine, a well-known bioactive compound found from medicinal plants, has been known to have anti-inflammatory, antimicrobial effects. To determine protective effect of BC in aminoglycoside-induced ototoxicity, hair cell damages in aminoglycoside- and/or BC-treated hair cells using ex vivo organotypic culture system of mouse cochlea. Mitochondrial ROS levels and depolarization of mitochondrial membrane potential were analyzed, and TUNEL assay and immunostaining of cleaved caspase-3 were performed to detect apoptosis signals. As the results, it was found that BC significantly prevented aminoglycoside-induced hair cell loss and stereocilia degeneration by inhibiting excessive accumulation of mitochondrial ROS and subsequent loss of mitochondrial membrane potential. It eventually inhibited DNA fragmentation and caspase-3 activation, which were significant for all three aminoglycosides. This study is the first report suggested the preventative effect of BC against aminoglycoside-induced ototoxicity. Our data also suggests a possibility that BC has the potential to exert a protective effect against ototoxicity caused by various ototoxic drugs leading to cellular oxidative stress, not limited to aminoglycoside antibiotics. [Display omitted] •Aminoglycoside results in ototoxicity due to the overproduction of reactive oxygen species.•Berberine chloride prevents aminoglycoside-provoked increase in ROS production in cochlear explants.•Berberine chloride reduced apoptotic cell death of hair cells in cisplatin-treated cochlear explants.