Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice

PLoS One. 2024 Apr 22;19(4):e0301379. doi: 10.1371/journal.pone.0301379. eCollection 2024.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Doxorubicin
  • Antibiotics, Antineoplastic

Grants and funding

Deminice R. is supported by CNPq #306842/2021-1 and #403232-2021-0, and by Fundação Araucaria. Cella P.S. is funded by CNPq #168165/2022-8 and Capes. Moura F.A. is supported by CNPq # #401004/2022-8, #200290/2022-3, #305997/2022-0, and #404473/2023-7. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.