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May 14, 2026Physiology

Effect of age on the development of acute Doxorubicin-induced respiratory muscle dysfunction

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Why the study?

Factors influencing susceptibility to doxorubicin respiratory toxicity are unclear, and the age-dependent physiological effects of doxorubicin on respiratory function remain underexplored.

Does doxorubicin reduce respiratory function and cardiorespiratory capacity in 2- and 20-month-old female Sprague-Dawley rats?

Population

2- and 20-month-old female Sprague-Dawley rats

Comparison

DOX treatment (20 mg/kg, IP) across 2- vs 20-month-old rats

Design

Preclinical animal study

Follow-up

48 hours

Key result

Acute doxorubicin treatment (20 mg/kg) negatively impacted respiratory muscle function and decreased exercise run time to fatigue in both 2- and 20-month-old female rats.

Authors

JRJonel ReyesBNBranden NyugenIDImtiaz Dowllah

Discussion

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Overview

Doxorubicin leaves hypoxic ventilation unchanged; leaves open whether diaphragm weakness drives clinical fatigue in treated patients.

Key Points

  • This study aims to evaluate how age affects the physiological response of respiratory muscles to Doxorubicin treatment.
  • Utilized 2- and 20-month-old female Sprague-Dawley rats to represent pediatric and adult populations.
  • Conducted whole-body plethysmography and exercise tolerance tests before and after Doxorubicin treatment (20 mg/kg, IP).
  • Measured diaphragm muscle force, fatigue rate, plasma testosterone and progesterone levels, and mitochondrial concentrations of Doxorubicin and its metabolite.],
  • Doxorubicin treatment did not significantly affect respiration during hypoxic challenges.
  • Exercise run time to fatigue decreased with age and Doxorubicin treatment.
  • Testosterone levels decreased significantly in older rats compared to younger ones, with no differences in progesterone or mitochondrial concentrations between age groups.

Structured PICO

Does doxorubicin reduce respiratory function and cardiorespiratory capacity in 2- and 20-month-old female Sprague-Dawley rats?

P
Population
2- and 20-month-old female Sprague-Dawley rats
I
Intervention
Doxorubicin 20 mg/kg, IP
C
Comparator
Pre-treatment baseline
O
Outcome
Changes in respiratory function and cardiorespiratory capacity at 48 hourssurrogate

Acute doxorubicin treatment negatively impacts respiratory muscle function and exercise tolerance in both young and old female rats, with no age-dependent differences in diaphragm specific force production or mitochondrial drug concentration.

Cite This Study

Reyes et al. (2026) studied Doxorubicin-induced respiratory muscle dysfunction. Doxorubicin vs. Prior to treatment was evaluated on Changes in respiratory function and cardiorespiratory capacity. Acute doxorubicin treatment (20 mg/kg) negatively impacted respiratory muscle function and decreased exercise run time to fatigue in both 2- and 20-month-old female rats.

synapsesocial.com/papers/6a056647a550a87e60a1e5eahttps://doi.org/10.1152/physiol.2026.41.s1.2301047
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