Department of Otolaryngology Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, R.O.C.
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C.
In Vivo. 2022 May-Jun;36(3):1095-1105. doi: 10.21873/invivo.12807.
BACKGROUND/AIM: Gentamicin has been widely prescribed since the last two decades despite its ototoxicity and nephrotoxicity. Bisdemethoxycurcumin (BDMC) is an affordable and safe curcuminoid with medicinal properties. We aimed to understand the effects of BDMC on the gentamicin-induced hair cell damage in mouse cochlear UB/OC-2 cells, in order to elucidate the therapeutic potential of BDMC against gentamicin-induced ototoxicity.
We quantified the cell membrane potential and examined the regulators and cascade proteins in the intrinsic pathway of hair cell apoptosis. Mouse cochlear UB/OC-2 cells were treated with BDMC before exposure to gentamicin. The effects of BDMC on hair cell viability, mitochondrial function, and apoptosis-related proteins were examined by flow cytometry, western blot, and fluorescent staining.
Our results revealed that BDMC reversed gentamicin-mediated cycle arrest at the G/M phase, stabilizing the mitochondrial membrane potential, decreasing cleaved caspase proteins, and successfully reversing hair cell apoptosis.
BDMC is a potential agent for reducing gentamicin-induced ototoxicity.
背景/目的：尽管庆大霉素具有耳毒性和肾毒性，但在过去的二十年中，它仍被广泛应用。双去甲氧基姜黄素（BDMC）是一种具有药用价值且价格合理、安全的姜黄素类化合物。我们旨在了解 BDMC 对庆大霉素诱导的小鼠耳蜗 UB/OC-2 细胞毛细胞损伤的影响，以阐明 BDMC 对抗庆大霉素耳毒性的治疗潜力。
我们量化了细胞膜电位，并研究了毛细胞凋亡内在途径中的调节剂和级联蛋白。在暴露于庆大霉素之前，用 BDMC 处理小鼠耳蜗 UB/OC-2 细胞。通过流式细胞术、western blot 和荧光染色检测 BDMC 对毛细胞活力、线粒体功能和凋亡相关蛋白的影响。
我们的结果表明，BDMC 逆转了庆大霉素介导的 G/M 期细胞周期阻滞，稳定了线粒体膜电位，减少了裂解的 caspase 蛋白，并成功逆转了毛细胞凋亡。
BDMC 是一种减少庆大霉素耳毒性的潜在药物。
