Int Neurourol J.  2019 Feb;23(Suppl 1):S32-S39. 10.5213/inj.1938046.023.

Treadmill Exercise Ameliorates Chemotherapy-Induced Muscle Weakness and Central Fatigue by Enhancing Mitochondrial Function and Inhibiting Apoptosis

• Park SS
• Park HS
• Jeong H
• Kwak HB
• No MH
• Heo JW
• Yoo SZ
• Kim TW

• KMID: 2448805
• DOI: http://doi.org/10.5213/inj.1938046.023

Abstract

PURPOSE
Chemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage.
METHODS
DOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated.
RESULTS
DOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise.
CONCLUSIONS
Apoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.

Keyword

Chemotherapy; Doxorubicin; Muscle strength; Fatigue; Mitochondrial function; Apoptosis

MeSH Terms

Apoptosis*
Blotting, Western
Breast Neoplasms
DNA, Mitochondrial
Dorsal Raphe Nucleus
Doxorubicin
Drug Therapy
Fatigue*
Humans
Immunohistochemistry
Mitochondria
Models, Animal
Muscle Fatigue
Muscle Strength
Muscle Weakness*
Prostatic Neoplasms
Running
Serotonin
Tryptophan Hydroxylase
DNA, Mitochondrial
Doxorubicin
Serotonin
Tryptophan Hydroxylase