Department of Biomedicine, University of Basel, Basel, Switzerland.
Clinic for Otolaryngology, Head and Neck Surgery, University of Basel Hospital, Basel, Switzerland,
Audiol Neurootol. 2020;25(6):297-308. doi: 10.1159/000506796. Epub 2020 May 5.
Telmisartan is an angiotensin II receptor blocker that has pleiotropic effects and protective properties in different cell types. Moreover, telmisartan has also shown partial agonism on the peroxisome proliferator-activated receptor γ (PPAR-γ). Auditory hair cells (HCs) express PPAR-γ, and the protective role of PPAR-γ agonists on HCs has been shown.
The objective of this study was to investigate the effects of telmisartan on gentamicin-induced ototoxicity in vitro.
Cochlear explants were exposed to gentamicin with or without telmisartan, and/or GW9662, an irreversible PPAR-γ antagonist.
Telmisartan protected auditory HCs against gentamicin-induced ototoxicity. GW9662 completely blocked this protective effect, suggesting that it was mediated by PPAR-γ signaling. Exposure to GW9662 or telmisartan alone was not toxic to auditory HCs.
We found that telmisartan, via PPAR-γ signaling, protects auditory HCs from gentamicin-induced ototoxicity. Therefore, telmisartan could potentially be used in the future to prevent or treat sensorineural hearing loss.
替米沙坦是一种血管紧张素 II 受体阻滞剂,它在不同的细胞类型中具有多种作用和保护特性。此外,替米沙坦对过氧化物酶体增殖物激活受体 γ(PPAR-γ)也具有部分激动作用。听觉毛细胞(HCs)表达 PPAR-γ,并且已经证明了 PPAR-γ 激动剂对 HCs 的保护作用。
本研究旨在探讨替米沙坦对体外庆大霉素诱导的耳毒性的作用。
将耳蜗外植体暴露于庆大霉素和/或替米沙坦和/或 GW9662(一种不可逆的 PPAR-γ 拮抗剂)中。
替米沙坦可保护听觉 HCs 免受庆大霉素诱导的耳毒性。GW9662 完全阻断了这种保护作用,表明其是通过 PPAR-γ 信号传导介导的。单独暴露于 GW9662 或替米沙坦对听觉 HCs 没有毒性。
我们发现替米沙坦通过 PPAR-γ 信号传导途径保护听觉 HCs 免受庆大霉素诱导的耳毒性。因此,替米沙坦将来可能用于预防或治疗感觉神经性听力损失。