Long-term effects of the chronic administration of doxorubicin on aged skeletal muscle: An exploratory study in mice.

Autor: Moreira-Pais A; Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto (FADEUP) and Laboratory for Integrative and Translational Research in Population Health (ITR), 4200-450, Porto, Portugal; LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal; Centre for Research and Technology of Agro Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801, Vila Real, Portugal. Electronic address: alexandrapais@ua.pt., Ferreira R; LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal. Electronic address: ritaferreira@ua.pt., Baltazar T; LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal. Electronic address: baltazar.telmo@ua.pt., Neuparth MJ; Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto (FADEUP) and Laboratory for Integrative and Translational Research in Population Health (ITR), 4200-450, Porto, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116, Gandra, Portugal. Electronic address: mneuparth@hotmail.com., Vitorino R; iBiMED - Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal. Electronic address: rvitorino@ua.pt., Reis-Mendes A; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal. Electronic address: afreis.mendes@gmail.com., Costa VM; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal. Electronic address: veramcosta@ff.up.pt., Oliveira PA; Centre for Research and Technology of Agro Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801, Vila Real, Portugal. Electronic address: pamo@utad.pt., Duarte JA; UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116, Gandra, Portugal; Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116, Gandra, Portugal. Electronic address: jose.duarte@iucs.cespu.pt.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 12; Vol. 733, pp. 150650. Date of Electronic Publication: 2024 Sep 03.
DOI: 10.1016/j.bbrc.2024.150650
Abstrakt: The widely used chemotherapeutic drug doxorubicin (DOX) has been associated with adverse effects on the skeletal muscle, which can persist for years after the end of the treatment. These adverse effects may be exacerbated in older patients, whose skeletal muscle might already be impaired by aging. Nonetheless, the mediators responsible for DOX-induced myotoxicity are still largely unidentified, particularly the ones involved in the long-term effects that negatively affect the quality of life of the patients. Therefore, this study aimed to investigate the long-term effects of the chronic administration of DOX on the soleus muscle of aged mice. For that and to mimic the clinical regimen, a dose of 1.5 mg kg -1 of DOX was administered two times per week for three consecutive weeks in a cumulative dose of 9 mg kg -1 to 19-month-old male mice, which were sacrificed two months after the last administration. Body wasting and the atrophy of the soleus muscle, as measured by a decrease in the cross-sectional area of the soleus muscle fibers, were identified as long-term effects of DOX administration. The atrophy observed was correlated with increased reactive oxygen species production and caspase-3 activity. An impaired skeletal muscle regeneration was also suggested due to the correlation between satellite cells activation and the soleus muscle fibers atrophy. Systemic inflammation, skeletal muscle energy metabolism and neuromuscular junction-related markers do not appear to be involved in the long-term DOX-induced skeletal muscle atrophy. The data provided by this study shed light on the mediators involved in the overlooked long-term DOX-induced myotoxicity, paving the way to the improvement of the quality of life and survival rates of older cancer patients.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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