Formoterol attenuates increased oxidative stress and myosin protein loss in respiratory and limb muscles of cancer cachectic rats

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• dc.contributor.author Salazar Degracia, Anna
• dc.contributor.author Busquets, Silvia
• dc.contributor.author Argilés, Josep M.
• dc.contributor.author López Soriano, Francisco J.
• dc.contributor.author Barreiro Portela, Esther
• dc.date.accessioned 2019-01-11T08:23:45Z
• dc.date.available 2019-01-11T08:23:45Z
• dc.date.issued 2017
• dc.description.abstract Muscle mass loss and wasting are characteristic features of patients with chronic conditions including cancer. Therapeutic options are still scarce. We hypothesized that cachexia-induced muscle oxidative stress may be attenuated in response to treatment with beta2-adrenoceptor-selective agonist formoterol in rats. In diaphragm and gastrocnemius of tumor-bearing rats (108 AH-130 Yoshida ascites hepatoma cells inoculated intraperitoneally) with and without treatment with formoterol (0.3 mg/kg body weight/day for seven days, daily subcutaneous injection), redox balance (protein oxidation and nitration and antioxidants) and muscle proteins (1-dimensional immunoblots), carbonylated proteins (2-dimensional immunoblots), inflammatory cells (immunohistochemistry), and mitochondrial respiratory chain (MRC) complex activities were explored. In the gastrocnemius, but not the diaphragm, of cancer cachectic rats compared to the controls, protein oxidation and nitration levels were increased, several functional and structural proteins were carbonylated, and in both study muscles, myosin content was reduced, inflammatory cell counts were greater, while no significant differences were seen in MRC complex activities (I, II, and IV). Treatment of cachectic rats with formoterol attenuated all the events in both respiratory and limb muscles. In this in vivo model of cancer-cachectic rats, the diaphragm is more resistant to oxidative stress. Formoterol treatment attenuated the rise in oxidative stress in the limb muscles, inflammatory cell infiltration, and the loss of myosin content seen in both study muscles, whereas no effects were observed in the MRC complex activities. These findings have therapeutic implications as they demonstrate beneficial effects of the beta2 agonist through decreased protein oxidation and inflammation in cachectic muscles, especially the gastrocnemius.
• dc.description.sponsorship The study has been funded by Instituto de Salud Carlos-III, contract grant numbers, CIBERES, FIS 14/00713, Catalan Foundation of Pulmonology (FUCAP), contract grant numbers, FUCAP 2011, FUCAP 2012, and FUCAP 2016, Spanish Respiratory Society (SEPAR) 2016, and Spanish Ministry of Science and Innovation, contract grant number SAF 2011-26091. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• dc.format.mimetype application/pdf
• dc.identifier.citation Salazar-Degracia A, Busquets S, Argilés JM, López-Soriano FJ, Barreiro E. Formoterol attenuates increased oxidative stress and myosin protein loss in respiratory and limb muscles of cancer cachectic rats. PeerJ. 2017 Dec 13;5:e4109. DOI: 10.7717/peerj.4109
• dc.identifier.doi http://dx.doi.org/10.7717/peerj.4109
• dc.identifier.issn 2167-8359
• dc.identifier.uri http://hdl.handle.net/10230/36253
• dc.language.iso eng
• dc.publisher PeerJ Inc.
• dc.relation.ispartof PeerJ. 2017 Dec 13;5:e4109
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-26091
• dc.rights Copyright ©2017 Salazar-Degracia et al. This is an open access article distributed under the terms of the https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Contractile proteins
• dc.subject.keyword Diaphragm and gastrocnemius
• dc.subject.keyword Experimental cancer-induced cachexia
• dc.subject.keyword Formoterol treatment
• dc.subject.keyword Redox balance
• dc.title Formoterol attenuates increased oxidative stress and myosin protein loss in respiratory and limb muscles of cancer cachectic rats
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion