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Effect of statin on age-related hearing loss via drug repurposing
Institution:1. Department of Otolaryngology, Uijeongbu Eulji Medical Center, Uijeongbu 11749, Republic of Korea;2. Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Republic of Korea;3. Department of Medical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea;4. Department of Otorhinolaryngology, Konyang University College of Medicine, Daejeon 35365, Republic of Korea
Abstract: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.
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