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Macrophage depletion protects against cisplatin-induced ototoxicity and nephrotoxicity.
Sung, Cathy Yea Won; Hayase, Naoki; Yuen, Peter S T; Lee, John; Fernandez, Katharine; Hu, Xuzhen; Cheng, Hui; Star, Robert A; Warchol, Mark E; Cunningham, Lisa L.
Afiliación
  • Sung CYW; Laboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD, USA.
  • Hayase N; Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
  • Yuen PST; Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
  • Lee J; Laboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD, USA.
  • Fernandez K; Laboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD, USA.
  • Hu X; Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
  • Cheng H; Bioinformatics and Biostatistics Collaboration Core, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD, USA.
  • Star RA; Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
  • Warchol ME; Department of Otolaryngology, School of Medicine, Washington University, Saint Louis, MO, USA.
  • Cunningham LL; Laboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD, USA.
Sci Adv ; 10(30): eadk9878, 2024 Jul 26.
Article en En | MEDLINE | ID: mdl-39047106
ABSTRACT
Cisplatin is a widely used anticancer drug with notable side effects including ototoxicity and nephrotoxicity. Macrophages, the major resident immune cells in the cochlea and kidney, are important drivers of both inflammatory and tissue repair responses. To investigate the roles of macrophages in cisplatin-induced toxicities, we used PLX3397, a U.S. Food and Drug Administration-approved inhibitor of the colony-stimulating factor 1 receptor, to eliminate tissue-resident macrophages. Mice treated with cisplatin alone had considerable hearing loss (ototoxicity) and kidney injury (nephrotoxicity). Macrophage ablation resulted in significantly reduced hearing loss and had greater outer hair cell survival. Macrophage ablation also protected against cisplatin-induced nephrotoxicity, as evidenced by markedly reduced tubular injury and fibrosis. Mechanistically, our data suggest that the protective effect of macrophage ablation against cisplatin-induced ototoxicity and nephrotoxicity is mediated by reduced platinum accumulation in both the inner ear and the kidney. Together, our data indicate that ablation of tissue-resident macrophages represents an important strategy for mitigating cisplatin-induced ototoxicity and nephrotoxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Ototoxicidad / Macrófagos Límite: Animals Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Ototoxicidad / Macrófagos Límite: Animals Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos