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Metronomic 5-Fluorouracil Delivery Primes Skeletal Muscle for Myopathy but Does Not Cause Cachexia.
Campelj, Dean G; Timpani, Cara A; Cree, Tabitha; Petersen, Aaron C; Hayes, Alan; Goodman, Craig A; Rybalka, Emma.
Afiliación
  • Campelj DG; Institute for Health and Sport, Victoria University, Melbourne, VIC 8001, Australia.
  • Timpani CA; Australian Institute for Musculoskeletal Science (AIMSS), Inherited and Acquired Myopathy Program, Victoria University, St Albans, VIC 3021, Australia.
  • Cree T; Institute for Health and Sport, Victoria University, Melbourne, VIC 8001, Australia.
  • Petersen AC; Australian Institute for Musculoskeletal Science (AIMSS), Inherited and Acquired Myopathy Program, Victoria University, St Albans, VIC 3021, Australia.
  • Hayes A; Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, Melbourne, VIC 3021, Australia.
  • Goodman CA; Institute for Health and Sport, Victoria University, Melbourne, VIC 8001, Australia.
  • Rybalka E; Australian Institute for Musculoskeletal Science (AIMSS), Inherited and Acquired Myopathy Program, Victoria University, St Albans, VIC 3021, Australia.
Pharmaceuticals (Basel) ; 14(5)2021 May 17.
Article en En | MEDLINE | ID: mdl-34067869
Skeletal myopathy encompasses both atrophy and dysfunction and is a prominent event in cancer and chemotherapy-induced cachexia. Here, we investigate the effects of a chemotherapeutic agent, 5-fluorouracil (5FU), on skeletal muscle mass and function, and whether small-molecule therapeutic candidate, BGP-15, could be protective against the chemotoxic challenge exerted by 5FU. Additionally, we explore the molecular signature of 5FU treatment. Male Balb/c mice received metronomic tri-weekly intraperitoneal delivery of 5FU (23 mg/kg), with and without BGP-15 (15 mg/kg), 6 times in total over a 15 day treatment period. We demonstrated that neither 5FU, nor 5FU combined with BGP-15, affected body composition indices, skeletal muscle mass or function. Adjuvant BGP-15 treatment did, however, prevent the 5FU-induced phosphorylation of p38 MAPK and p65 NF-B subunit, signalling pathways involved in cell stress and inflammatory signalling, respectively. This as associated with mitoprotection. 5FU reduced the expression of the key cytoskeletal proteins, desmin and dystrophin, which was not prevented by BGP-15. Combined, these data show that metronomic delivery of 5FU does not elicit physiological consequences to skeletal muscle mass and function but is implicit in priming skeletal muscle with a molecular signature for myopathy. BGP-15 has modest protective efficacy against the molecular changes induced by 5FU.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceuticals (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceuticals (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza