Telmisartan Attenuates Kanamycin-Induced Ototoxicity in Rats

Chang Ho Lee,So Young Kim,So Min Lee

doi:10.3390/ijms222312716

Abstract

Telmisartan (TM) has been proposed to relieve inflammatory responses by modulating peroxisome proliferator activator receptor-γ (PPARγ) signaling. This study aimed to investigate the protective effects of TM on kanamycin(KM)-induced ototoxicity in rats. Forty-eight, 8-week-old female Sprague Dawley rats were divided into four groups: (1) control group, (2) TM group, (3) KM group, and (4) TM + KM group. Auditory brainstem response was measured. The histology of the cochlea was examined. The protein expression levels of angiotensin-converting enzyme 2 (ACE2), HO1, and PPARγ were measured by Western blotting. The auditory threshold shifts at 4, 8, 16, and 32 kHz were lower in the TM + KM group than in the KM group (all p < 0.05). The loss of cochlear outer hair cells and spiral ganglial cells was lower in the TM + KM group than in the KM group. The protein expression levels of ACE2, PPARγ, and HO1 were higher in the KM group than in the control group (all p < 0.05). The TM + KM group showed lower expression levels of PPARγ and HO1 than the KM group.TM protected the cochlea from KM-induced injuries in rats. TM preserved hearing levels and attenuated the increase in PPARγ and HO1 expression levels in KM-exposed rat cochleae.

Highlights

Telmisartan (TM) has been proposed to relieve inflammatory responses by modulating peroxisome proliferator activator receptor-γ (PPARγ) signaling
In addition to being an AngII type 1 receptor (AT1R) blocker, TM has been acknowledged as a partial agonist of peroxisome proliferator activator receptor-γ (PPARγ) [1,10]
The otoprotective effect of TM was accompanied by a decrease in oxidative stress-related protein levels of HO1 and PPARγ, which implied the mediating roles of antioxidative responses

Summary

Introduction

Telmisartan (TM) has been proposed to relieve inflammatory responses by modulating peroxisome proliferator activator receptor-γ (PPARγ) signaling. The protein expression levels of angiotensin-converting enzyme 2 (ACE2), HO1, and PPARγ were measured by Western blotting. The protein expression levels of ACE2, PPARγ, and HO1 were higher in the KM group than in the control group (all p < 0.05). The TM + KM group showed lower expression levels of PPARγ and HO1 than the KM group.TM protected the cochlea from KM-induced injuries in rats. As an AT1R antagonist, TM decreases the angiotensin-converting enzyme (ACE)/AngII/AT1 axis and increases ACE2/Ang(1-7)/Mas axis activation [5]. Recent studies suggested that the antagonizing action for the production of AngII and anti-inflammatory responses of TM could exert therapeutic effects on COVID-19 [9]. PPARγ plays a role in maintaining the homeostasis of lipid and glucose metabolism and inflammatory cells [11,12]

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