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Quercetin attenuates cisplatin-induced mitochondrial apoptosis via PI3K/Akt mediated inhibition of oxidative stress in pericytes and improves the blood labyrinth barrier permeability.
Huang, Tian-Lan; Jiang, Wen-Jun; Zhou, Zan; Shi, Tian-Feng; Yu, Miao; Yu, Meng; Si, Jun-Qiang; Wang, Yan-Ping; Li, Li.
Afiliación
  • Huang TL; Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang, 832000, China.
  • Jiang WJ; Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310051, China; Department of Physiology, Medical College of Jiaxing University, Jiaxing, Zhejiang, 314000, China.
  • Zhou Z; Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang, 832000, China.
  • Shi TF; Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang, 832000, China.
  • Yu M; Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang, 832000, China.
  • Yu M; Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310051, China; Department of Physiology, Medical College of Jiaxing University, Jiaxing, Zhejiang, 314000, China.
  • Si JQ; Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang, 832000, China.
  • Wang YP; Department of Nursing, Medical College of Jiaxing University, Jiaxing, Zhejiang, 314000, China. Electronic address: yanping7155@163.com.
  • Li L; Department of Physiology, Medical College of Jiaxing University, Jiaxing, Zhejiang, 314000, China. Electronic address: lily7588@163.com.
Chem Biol Interact ; 393: 110939, 2024 Apr 25.
Article en En | MEDLINE | ID: mdl-38490643
ABSTRACT
Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc. Oxidative stress levels, mitochondrial function and endothelial barrier changes were observed in vitro by using DCFH-DA probe detection, flow cytometry, JC-1 probe, immunofluorescence and the establishment in vitro BLB models, etc. QU pretreatment activates the PI3K/AKT signaling pathway, inhibits CDDP-induced oxidative stress, protects mitochondrial function, and reduces mitochondrial apoptosis in PCs. However, PI3K/AKT specific inhibitor (LY294002) partially reverses the protective effects of QU. In addition, in vitro BLB models were established by coculturing PCs and endothelial cells (ECs), which suggests that QU both reduces the CDDP-induced apoptosis in PCs and improves the endothelial barrier permeability. On the whole, the research findings suggest that QU can be used as a novel treatment to reduce CDDP-induced ototoxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Ototoxicidad Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Ototoxicidad Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda