1. Academic Validation
  2. Metformin attenuates cadmium-induced degeneration of spiral ganglion neuron via restoring autophagic flux in primary culture

Metformin attenuates cadmium-induced degeneration of spiral ganglion neuron via restoring autophagic flux in primary culture

  • J Inorg Biochem. 2022 Sep;234:111901. doi: 10.1016/j.jinorgbio.2022.111901.
Qian Li 1 Liuqian Wang 1 Di Ji 1 Wei Yu 1 Yan Zhang 1 Yanghong Xiang 1 Chao Zhou 2 Liting Wang 3 Ping Deng 2 Huifeng Pi 2 Yonghui Lu 2 Qinlong Ma 2 Mindi He 2 Lei Zhang 2 Zhengping Yu 2 Anchun Deng 4
Affiliations

Affiliations

  • 1 Department of Otolaryngology Head and Neck Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
  • 2 Department of Occupational Health, Army Medical University (Third Military Medical University), Chongqing, China.
  • 3 Biomedical Analysis Center, Army Medical University (Third Military Medical University), Chongqing, China.
  • 4 Department of Otolaryngology Head and Neck Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China. Electronic address: taurusli@163.com.
Abstract

Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for hearing loss. After exposure, Cd accumulates in the inner ear and induces spiral ganglion neuron (SGN) degeneration; however, the underlying mechanisms are poorly understood. Dysfunctional Autophagy has been implicated in many neurodegenerative diseases, including Cd-induced neurotoxicity. Metformin has been validated to confer not only anti-hyperglycaemic but also neuroprotective effects. However, the relationship between Autophagy dysfunction, SGN degeneration, and the effect of metformin on Cd-induced SGN neurotoxicity has not yet been established. In this study, we demonstrate that metformin notably attenuates Cd-evoked SGN degeneration by restoring impaired Autophagy flux, as evidenced by the suppression of Cd-induced elevation of Autophagy markers microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and Autophagy substrate protein p62 in degenerated SGN. Blockage of Autophagy flux by chloroquine abolished metformin-induced neuroprotection against Cd-induced neurotoxicity in SGN. The results of this study reveal that Autophagy dysfunction is an important component of Cd-induced SGN degeneration, and metformin may be a potential protective agent for attenuating SGN degeneration following Cd exposure.

Keywords

Autophagy; Cadmium; Hearing loss; Metformin; Neurotoxicity; Spiral ganglion neuron.

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