Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Doxorubicin*/adverse effects ; Cachexia*/chemically induced ; Cachexia*/etiology ; Sarcopenia*/chemically induced ; Sarcopenia*/pathology ; Frailty* ; Mice, Inbred C57BL* ; Muscle, Skeletal*/drug effects ; Muscle, Skeletal*/pathology; Animals ; Mice ; Male ; Muscle Strength/drug effects ; Muscular Atrophy/chemically induced ; Muscular Atrophy/pathology ; Weight Loss/drug effects ; Antibiotics, Antineoplastic/adverse effects ; Antibiotics, Antineoplastic/toxicity

Competing Interests: The authors have declared that no competing interests exist.
While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.
(Copyright: © 2024 Cella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cancer Manag Res. 2020 Jul 09;12:5597-5605. (PMID: 32753972)
Ann Oncol. 2015 Jun;26(6):1091-1101. (PMID: 25403592)
J Cachexia Sarcopenia Muscle. 2021 Jun;12(3):538-554. (PMID: 33951340)
Antioxidants (Basel). 2023 Mar 28;12(4):. (PMID: 37107198)
Ann Surg Oncol. 2018 Oct;25(11):3372-3379. (PMID: 30069659)
Sleep Sci. 2016 Jul-Sep;9(3):232-235. (PMID: 28123667)
Ann Surg Oncol. 2015 Aug;22(8):2663-8. (PMID: 25564158)
J Cachexia Sarcopenia Muscle. 2018 Apr;9(2):315-325. (PMID: 29318756)
Am J Physiol Lung Cell Mol Physiol. 2011 Feb;300(2):L225-31. (PMID: 21097524)
Brain Behav Immun. 2012 Jul;26(5):699-705. (PMID: 22251605)
Nat Methods. 2022 Apr;19(4):496-504. (PMID: 35414125)
J Appl Physiol (1985). 2009 Dec;107(6):1935-42. (PMID: 19779154)
Int J Colorectal Dis. 2021 Jun;36(6):1077-1096. (PMID: 33481108)
Nutr Cancer. 2020;72(2):252-259. (PMID: 31184509)
Lancet Oncol. 2011 May;12(5):489-95. (PMID: 21296615)
Oncologist. 2018 Oct;23(10):1153-1161. (PMID: 30120159)
JPEN J Parenter Enteral Nutr. 2021 Nov;45(S2):16-25. (PMID: 34897740)
Clin Interv Aging. 2023 Mar 28;18:505-521. (PMID: 37013130)
CA Cancer J Clin. 2017 Sep;67(5):362-377. (PMID: 28731537)
Drug Des Devel Ther. 2015 Dec 14;9:6433-44. (PMID: 26715840)
Anticancer Res. 2011 Jun;31(6):2023-8. (PMID: 21737618)
Oncogenesis. 2021 Jan 8;10(1):1. (PMID: 33419963)
Int J Sports Med. 2012 Apr;33(4):268-78. (PMID: 22261826)
Sci Rep. 2020 Sep 24;10(1):15044. (PMID: 32973229)
Antioxidants (Basel). 2020 Mar 23;9(3):. (PMID: 32210013)
Brain Behav Immun. 2014 Mar;37:84-94. (PMID: 24216337)
Med Sci Sports Exerc. 2020 Jul;52(7):1477-1484. (PMID: 31985575)
J Cachexia Sarcopenia Muscle. 2019 Feb;10(1):140-154. (PMID: 30680954)
Tech Innov Patient Support Radiat Oncol. 2020 Nov 09;16:50-57. (PMID: 33385074)
JPEN J Parenter Enteral Nutr. 2009 Jul-Aug;33(4):361-7. (PMID: 19109514)
J Cachexia Sarcopenia Muscle. 2016 Dec;7(5):615-625. (PMID: 27239415)
Cancer Chemother Pharmacol. 2023 Nov;92(5):357-367. (PMID: 37582913)
BMC Cancer. 2020 Mar 4;20(1):172. (PMID: 32131764)
J Gerontol A Biol Sci Med Sci. 2021 Apr 30;76(5):819-824. (PMID: 32822475)
Front Physiol. 2017 Sep 29;8:715. (PMID: 29033844)
J Appl Physiol (1985). 2014 Aug 1;117(3):223-30. (PMID: 24947024)
J Physiol. 2015 Apr 15;593(8):2017-36. (PMID: 25643692)
Nat Neurosci. 2018 Sep;21(9):1281-1289. (PMID: 30127430)
Oncology. 2012;83(6):305-20. (PMID: 22964943)
BMC Geriatr. 2021 Jun 2;21(1):339. (PMID: 34078275)
JPEN J Parenter Enteral Nutr. 2022 Nov;46(8):1761-1768. (PMID: 35633306)
Acta Physiol (Oxf). 2020 Jun;229(2):e13400. (PMID: 31600860)
Sci Rep. 2016 Sep 26;6:32695. (PMID: 27666826)
J Gerontol A Biol Sci Med Sci. 2014 Jun;69(6):621-32. (PMID: 24051346)

80168379AG (Doxorubicin)
0 (Antibiotics, Antineoplastic)

Date Created: 20240422 Date Completed: 20240429 Latest Revision: 20240429

20250114

PMC11034664

10.1371/journal.pone.0301379

38648220