Telmisartan attenuates gentamicin-induced ototoxicity and modulates oxidative stress and RhoA/ROCK-associated...

Gentamicin-induced ototoxicity involves oxidative stress, inflammation, mitochondrial dysfunction, and cochlear hair-cell injury. This study evaluated the protective effects of telmisartan and their association with RhoA/ROCK signaling in mice. Male C57BL/6J mice were assigned to normal control, gentamicin control, gentamicin plus fasudil (2 mg/kg), or gentamicin plus telmisartan (5, 10, or 20 mg/kg) groups (n = 10). Auditory function was assessed by auditory brainstem response, while locomotor and gait performance were evaluated using open-field and gait tests. Cochlear oxidative stress, inflammatory biomarkers, RhoA activation, ROCK1/2 mRNA expression, and ROCK-associated protein phosphorylation were assessed using colorimetric assays, ELISA, fluorescence imaging, qRT-PCR, and Western blotting. Hair-cell integrity was evaluated by MYO7A immunofluorescence, quantitative counting, and histopathology. Gentamicin elevated auditory thresholds, prolonged shock-avoidance response latencies, impaired locomotor and gait performance, increased intracellular and mitochondrial reactive oxygen species, and reduced antioxidant defenses. It also increased iNOS, NF-κB, active RhoA, ROCK1/2 expression, and phosphorylation of ROCK-associated proteins while reducing MYO7A-positive hair-cell density. Fasudil and telmisartan attenuated these alterations, with higher telmisartan doses generally providing greater protection, although responses were not uniformly dose-dependent. Telmisartan also preserved sensory epithelial organization and cochlear hair-cell density. Telmisartan attenuated gentamicin-associated auditory and cochlear injury, with effects associated with reduced oxidative and inflammatory stress and modulation of RhoA/ROCK-related signaling. Further pathway-specific and clinically relevant studies are required.