2. Academic Validation
  3. Protection by maslinic acid against cisplatin-induced ototoxicity: rescue of ferroptosis by targeting the SLC7A11-GSH-GPX4 pathway

Protection by maslinic acid against cisplatin-induced ototoxicity: rescue of ferroptosis by targeting the SLC7A11-GSH-GPX4 pathway

  • Biochem Biophys Res Commun. 2026 Apr 16:809:153480. doi: 10.1016/j.bbrc.2026.153480.
Qingru Cheng 1,  Mengqi Jian 1,  Wenhui Li 1,  Chong Zhao 2
Affiliations

Affiliations

  • 1 College of Food Science and Nutritional Engineering, China Agricultural University, No 17, Qinghua East Road, Haidian District, Beijing, 100083, China.
  • 2 College of Food Science and Nutritional Engineering, China Agricultural University, No 17, Qinghua East Road, Haidian District, Beijing, 100083, China; China Agricultural University-Sichuan Advanced Agricultural & Industrial Institute, No 515, Xingyuan Road, Xinjin District, Chengdu, 611400, China. Electronic address: [email protected].
PMID: 41722247 DOI: 10.1016/j.bbrc.2026.153480
Abstract

Cisplatin (CP) chemotherapy often causes ototoxicity, a major side effect. Maslinic acid (MA), a pentacyclic triterpenoid with known anti-inflammatory and antioxidant properties, was investigated for its protection against CP-induced hearing loss. In vivo, MA maintained the hearing threshold of CP-treated mice at 50-60 dB SPL and prevented damage to the stria vascularis and spiral ganglion. Proteomic analysis indicated that MA reduces ototoxicity by inhibiting oxidative stress and Ferroptosis pathways. In vitro, MA counteracted the loss of HEI-OC1 cell viability induced by CP or the Ferroptosis inducer sulfasalazine (SAS), while suppressing Ferroptosis markers such as lipid peroxidation, ROS, and MDA. Mechanistically, MA promoted membrane localization of SLC7A11, enhancing cysteine uptake and activity, and upregulated GPX4 expression, thereby strengthening cellular resistance to Ferroptosis. These results support further development of MA as a therapeutic agent against cisplatin-induced ototoxicity.

Keywords

Cisplatin; Ferroptosis; Maslinic acid; Ototoxicity; SLC7A11.

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