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Antioxidant Treatment of Muscle Wasting and Fatigue in Tumor-Bearing Mice

Clark, Yvonne Yumiko
http://rave.ohiolink.edu/etdc/view?acc_num=osu1373844738

Abstract Details

2013, Doctor of Philosophy, Ohio State University, Nursing.
Purpose: Fatigue is the most common and distressing symptom reported by cancer patients, significantly reducing quality of life. While the mechanisms of cancer-related fatigue (CRF) are poorly understood, evidence indicates that pro-inflammatory cytokines and reactive oxygen species, produced by the tumor and/or host, alter muscle metabolism to cause muscle wasting and cardiac dysfunction. Symptoms of muscle wasting and cardiac dysfunction are weakness and decreased effort tolerance, similar to patients with CRF. Ubiquinol, an endogenously produced, lipid soluble antioxidant, protects against lipid peroxidation to cellular lipid membranes, proteins and DNA, and regenerates active forms of other antioxidants such as vitamins C and E. The purpose of this study was to determine if treatment with ubiquinol, might preserve muscle mass, improve cardiac function, and reduce fatigue in an animal model of CRF. The following hypotheses were tested in mice bearing the colon26 (C26) adenocarcinoma: 1. Ubiquinol will reduce the expression of biomarkers of muscle protein degradation and increase protein synthesis in the gastrocnemius and cardiac muscles of tumor-bearing mice; 2. Ubiquinol will increase: (a) muscle mass, (b) fore-limb grip strength, (c) in vivo cardiac function, and (d) voluntary running activity (VRA) in tumor-bearing mice and; 3. Ubiquinol will not affect tumor growth. Method: Eight week old adult female CD2F1 mice were acclimated to running wheels and grip strength 1 week prior to being inoculated with the tumor cells. Half of the control and half of the tumor bearing mice received ubiquinol 500 mg/kg/day in their drinking water. VRA and grip strength were measured on days 0, 8, 14 and 17 of tumor growth. Cardiac function was measured by echocardiography on day 18 or 19 after which the mice were euthanized. The heart and gastrocnemius muscles were weighed and normalized to body weight. Serum levels of proinflammatory cytokines were measured by ELISA. Oxidative stress was measured in skeletal and cardiac muscle homogenates. Skeletal and cardiac muscle expression of genes reflecting muscle inflammation and biomarkers associated with muscle metabolism were determined using real time-PCR. Results: Tumor growth induced loss of muscle mass and decreased VRA and grip strength. Tumor growth also increased serum and muscle levels of pro-inflammatory cytokines, oxidative stress in cardiac muscle, altered cardiac function and biomarkers associated with muscle metabolism in skeletal muscle. Echocardiography revealed a diastolic dysfunction in the tumor-bearing mice. Treatment with ubiquinol did not alter levels of proinflammatory cytokines in serum and skeletal and cardiac muscle, oxidative stress in cardiac muscle, biomarkers associated with muscle metabolism, cardiac function, VRA or grip strength in the tumor-bearing mice, but did increase skeletal muscle mass. Conclusion: These data confirm prior studies indicating tumor growth alone affects cardiac function, which could contribute to CRF. Because ubiquinol improved muscle mass without affecting measures of fatigue and weakness, inflammation, cardiac function or muscle metabolism, we conclude that antioxidant treatment alone is not likely to reverse CRF. These data also suggest that skeletal muscle wasting may not be a major factor in reduced physical activity and weakness associated with CRF.
Donna McCarthy, PhD (Advisor)
Loren Wold, PhD (Committee Member)
Jodi McDaniel, PhD (Committee Member)
Laura Szalacha, PhD (Committee Member)
99 p.
Physiology
cancer related fatigue; antioxidant; muscle wasting

Recommended Citations

Citations

  • Clark, Y. Y. (2013). Antioxidant Treatment of Muscle Wasting and Fatigue in Tumor-Bearing Mice [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1373844738

    APA Style (7th edition)

  • Clark, Yvonne. Antioxidant Treatment of Muscle Wasting and Fatigue in Tumor-Bearing Mice. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1373844738.

    MLA Style (8th edition)

  • Clark, Yvonne. "Antioxidant Treatment of Muscle Wasting and Fatigue in Tumor-Bearing Mice." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1373844738

    Chicago Manual of Style (17th edition)

osu1373844738
636
© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.