Abstract
Doxorubicin (DOX) is a chemotherapy agent widely used to treat many types of cancer; however, DOX use is limited due to its adverse effects. Skeletal muscle wasting and weakness are among the significant adverse effects that can decrease quality of life in cancer patients. DOX’s lasting and late effects on skeletal muscle, after the cessation of treatment, have yet to be elucidated. PURPOSE: This study aims to investigate the effects of DOX on skeletal muscle function in rats following a 6-week recovery period after DOX treatment. METHODS: 21 male Wistar rats (10 weeks old) were assigned into two groups: Control (C, n=9) and DOX (D, n=12). DOX group received weekly doxorubicin injections (I.P., 2.5mg/kg) for 4 weeks, while C received equal volume of saline solution Skeletal muscle function was evaluated at the end of DOX treatment (baseline) and following a 6-week recovery period (final) by electrically stimulating the plantar flexor muscles at several frequencies (20, 40, 60, 80, 100, 120 Hz). Briefly, rats were anesthetized, and the left foot was securely anchored to a footplate, and the muscles were stimulated by two percutaneous needle electrodes placed beside the gastrocnemius muscle to elicit plantar flexion of the foot. A torque–frequency curve was generated, maximal muscle torque (nN/m) was recorded for each timepoint, and the percentage change from baseline was calculated. At the end of the experiment, rats were euthanized, and the tibia bone was measured to assess the animal’s growth rate. T-tests were used to compare differences between the experimental groups for each frequency. Statistical significance is set at p < 0.05. RESULTS: At the final timepoint, tibia length was used to assess the animal’s growth factor, which was not significantly different between the C and D groups. Regarding skeletal muscle function, we observed a significant difference in percentage change of maximal muscle torque at low but not moderate or high frequencies (20Hz, C: 35.72 ± 25.97 and D: 3.02 ± 19.13 p = 0.008; 40Hz, C: 34.19 ± 33.64 and D: 4.69 ± 21.91 p = 0.041; 60Hz, C: 31.59 ± 21.35 and D: 16.08 ± 15.77 p = 0.091; 80Hz, C: 33.63 ± 22.86 and D: 22.47 ± 10.67 p = 0.208, 100HZ, C: 32.87 ± 21.54 and D: 18.24 ± 14.64 p = 0.105; 120Hz, C: 32.42 ± 20.74 and D: 18.08 ± 15.41 p = 0.106). CONCLUSION: Rats exposed to DOX showed a reduced gain in muscle torque during the recovery period, suggesting that DOX effects on skeletal muscle function continue even after cessation of treatment. Since this reduction was observed only at low frequencies of stimulation, we believe that this effect may be related to oxidative stress or calcium handling impairment caused during DOX treatment; however, further analyses are needed.
Recommended Citation
Meka, Riya; Pigg, Quinten W.; Harris, Dillon R.; Yoshimura, Daniela Inoue; and Gomes, Mariana Janini
(2026)
"Lasting Effects of Doxorubicin on Skeletal Muscle Function During Recovery in Rats,"
International Journal of Exercise Science: Conference Proceedings: Vol. 2:
Iss.
18, Article 137.
Available at:
https://digitalcommons.wku.edu/ijesab/vol2/iss18/137