Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis

Qilei Zhang; Yunhao Wu; Yan Yu; Yuguang Niu; Qiaojun Fang; Xin Chen; Jieyu Qi; Chen Zhang; Geping Wu; Kaiming Su; Renjie Chai

doi:10.3389/fbioe.2022.876237

Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis

Front Bioeng Biotechnol. 2022 Apr 20:10:876237. doi: 10.3389/fbioe.2022.876237. eCollection 2022.

Authors

Qilei Zhang¹, Yunhao Wu², Yan Yu¹, Yuguang Niu³, Qiaojun Fang², Xin Chen², Jieyu Qi², Chen Zhang⁴, Geping Wu¹, Kaiming Su⁵, Renjie Chai^{2

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Affiliations

¹ The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China.
² State Key Laboratory of Bioelectronics, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, China.
³ Department of Ambulatory Medicine, the First Medical Center of PLA General Hospital, Beijing, China.
⁴ Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
⁵ Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
⁶ Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁷ Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
⁸ Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, China.
⁹ Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China.

Abstract

Aminoglycoside antibiotics are widely used for the treatment of serious acute infections, life-threatening sepsis, and tuberculosis, but all aminoglycosides cause side effects, especially irreversible ototoxicity. The mechanisms underlying the ototoxicity of aminoglycosides need further investigation, and there are no effective drugs in the clinic. Here we showed that tetrandrine (TET), a bioactive bisbenzylisoquinoline alkaloid derived from Stephania tetrandra, ameliorated neomycin-induced cochlear hair cell injury. In both in vitro and in vivo experiments we found that TET administration significantly improved auditory function and reduced hair cell damage after neomycin exposure. In addition, we observed that TET could significantly decrease oxidative stress and apoptosis in hair cells after neomycin exposure. Finally, RNA-seq analysis suggested that TET protected against neomycin-induced ototoxicity mainly by promoting steroid biosynthesis. Collectively, our results provide pharmacological evidence showing that TET may be a promising agent in preventing aminoglycosides-induced ototoxicity.

Keywords: apoptosis; hair cell; oxidative stress; steroid biosynthesis; tetrandrine.