2. Academic Validation
  3. Ferroptosis is involved in PGPS-induced otitis media in C57BL/6 mice

Ferroptosis is involved in PGPS-induced otitis media in C57BL/6 mice

  • Cell Death Discov. 2022 Apr 21;8(1):217. doi: 10.1038/s41420-022-01025-1.
Bin Yan  # 1 2,  Daoli Xie  # 1,  Yuancheng Wu 1,  Shuli Wang 1,  Xiaolin Zhang 3,  Tong Zhao 1,  Luying Liu 4,  Peng Ma 5,  Guqiang Li 2,  Ying Yang 1,  Yucheng Zhao 1,  Tihua Zheng 1,  Ruishuang Geng 6,  Bo Li 7,  Qingyin Zheng 8
Affiliations

Affiliations

  • 1 Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, Yantai, China.
  • 2 Rehabilitation Medicine & Physical Therapy, School of Rehabilitation Medicine, Binzhou Medical University, Yantai, China.
  • 3 Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou, China.
  • 4 Department of Pathology, School of Basic Medicine, Binzhou Medical University, Yantai, China.
  • 5 Department of Genetics, School of Basic Medicine, Binzhou Medical University, Yantai, China.
  • 6 Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, Yantai, China. gengruishuang@hotmail.com.
  • 7 Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, Yantai, China. liboyjt@163.com.
  • 8 Department of Otolaryngology-Head & Neck Surgery, Case Western Reserve University, Cleveland, OH, USA.
  • # Contributed equally.
PMID: 35449198 DOI: 10.1038/s41420-022-01025-1
Abstract

Otitis media (OM) is a common disease that can cause hearing loss in children. Currently, the main clinical treatment for OM is Antibiotics, but the overuse of Antibiotics might lead to Bacterial resistance, which is a worldwide public health challenge. Studying the pathogenesis of OM will help us develop new effective treatments. Ferroptosis is one type of programmed cell death characterized by the occurrence of lipid peroxidation driven by iron ions. Many studies have shown that Ferroptosis is associated with infectious diseases. It is presently unclear whether Ferroptosis is involved in the pathogenesis of OM. In this study, we explored the relationship between Ferroptosis and OM by PGPS-induced OM in C57BL/6 mice and treating the induced OM with Ferroptosis inhibitors deferoxamine (DFO), Ferrostatin-1 (Fer-1), and Liperoxstatin-1 (Lip-1). We examined the expression of ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and prostaglandin-endoperoxide synthase 2 (Cox2), Glutathione Peroxidase 4 (GPX4) protein as well as lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). The results showed that in PGPS-induced OM model mice, several ferroptosis-related proteins including ACSL4 and Cox2 were up-regulated compared to mice treated with saline. Meanwhile, a ferroptosis-related protein GPX4 was down-regulated upon PGPS treatment. The DFO treatment in PGPS-inoculated mice effectively inhibited the development of OM. The inhibitors treatment caused a significant decrease in the expression of ACSL4, Cox2, 4 HNE, MDA, reduction in free iron. Meanwhile, the Ferroptosis inhibitors treatment caused increase in the expression of inflammation-related factors tumor necrosis factor-α (TNF-α) and antioxidant protein GPX4. Our results suggest that there is a crosstalk between Ferroptosis signaling pathway and the pathogenesis of OM. Ferroptosis inhibition can alleviate PGPS-induced OM.

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