Department of Otolaryngology, Uijeongbu Eulji Medical Center, Uijeongbu 11749, Republic of Korea.
Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Biochim Biophys Acta Mol Cell Res. 2022 Nov;1869(11):119331. doi: 10.1016/j.bbamcr.2022.119331. Epub 2022 Aug 11.
Hearing loss in the elderly cause communication difficulties, decreased quality of life, isolation, loneliness and frustration. The aim of our study was to investigate the effect of drug repurposing candidates in aging mouse. The selected candidate drugs for age-related hearing loss (ARHL) included atorvastatin (AS) and sarpogrelate. Monotherapy or fixed dose combination (FDC) products were administered via oral gavage for 6 consecutive months. Auditory outcomes showed significant hearing preservation in AS-treated aging mice compared to aging control, especially in the early stages of ARHL in both 8 and 16 kHz frequencies. However, none of the FDC products were able to prevent ARHL regardless of AS involvement. In aging mice, damage and dysfunction of mitochondria was noted as well as reactive oxygen species overproduction leading to oxidative stress and intrinsic apoptosis. These processes of ARHL were significantly prevented with administration of AS. Normal structures of mitochondria were maintained, and antioxidant activity were proceeded by activation of HSF1/Sirt1 pathway. Our study suggests that AS is a promising drug repurposing candidate to delay the progression of ARHL.
老年人听力损失导致沟通困难、生活质量下降、孤立、孤独和沮丧。我们的研究旨在研究药物再利用候选物在衰老小鼠中的作用。选择用于与年龄相关的听力损失（ARHL）的候选药物包括阿托伐他汀（AS）和沙格雷酯。通过口服灌胃连续 6 个月给予单一药物治疗或固定剂量组合（FDC）产品。听觉结果显示，与衰老对照组相比，AS 治疗的衰老小鼠的听力保存有显著改善，尤其是在 8 和 16 kHz 频率的 ARHL 的早期阶段。然而，无论是否涉及 AS，任何 FDC 产品都无法预防 ARHL。在衰老的小鼠中，线粒体的损伤和功能障碍以及活性氧的过度产生导致氧化应激和内在凋亡。用 AS 给药可显著预防 ARHL 的这些过程。通过激活 HSF1/Sirt1 通路，维持了线粒体的正常结构，并进行了抗氧化活性。我们的研究表明，AS 是一种有前途的药物再利用候选物，可以延缓 ARHL 的进展。
