First Advisor

Hydock, David S.

Degree Name

Master of Science

Document Type

Thesis

Date Created

8-2019

Department

College of Natural and Health Sciences, Kinesiology Nutrition and Dietetics, KiND Student Work

Embargo Date

8-1-2019

Abstract

Doxorubicin (DOX) is an effective chemotherapeutic drug for many types of cancer. However, the deleterious effect of DOX is also observed in heart and skeletal muscles. Doxorubicin-induced reactive oxygen species (ROS) in mitochondria causes muscle dysfunction and atrophy leading to the release of cytochrome c (cyt c) and activation of caspase-9 (casp-9) which cause apoptosis, a programmed cell death in skeletal muscles. Previous studies have proposed that creatine (Cr) possesses antioxidant capacity by reducing ROS in oxidative environment. Creatine supplements have shown to reduce mitochondrial ROS production and decrease apoptotic enzyme activities in oxidative skeletal muscles; however, Cr’s effects on DOX-induced apoptosis are not yet fully understood. PURPOSE: To investigate the effects of two different Cr supplementation protocols on cyt c and casp-9 expression in skeletal muscles from rats treated with DOX at two different time points. METHODS: Male Sprague Dawley rats (n=120) were randomly assigned to one of the three different diet treatments: control (CON, n=40), 2% Cr for four-week (2% Cr, n=40), and the Cr loading consisting of 4% Cr for one-week followed by three-week of 2% Cr (4% Cr, n=40). Then, each group was randomly assigned to two different time points for the drug administration: one-day prior to the sacrifice (1, n=20) and three-day prior to the sacrifice (3, n=20). Lastly, each group was randomly assigned to two different drug treatments: 3 mL of saline (SAL, n=10) and 15 mg/kg of DOX (DOX, n=10). The left soleus (SOL) and left extensor digitorum longus (EDL) were collected after anesthesia and homogenized. A western blot assay was used to determine protein expression of cyt c and casp-9. RESULTS: No significant effects of Cr supplementation and DOX administration on cyt c and casp-9 expressions were observed in both the SOL and EDL (p>0.05). The interaction between the Cr supplementation and the DOX injection was also not significant (p>0.05). A trend toward a decrease in cyt c and casp-9 expression was observed in the 4% Cr group of 3 SOL and 1-EDL with the DOX injection, but there were no significant differences (p>0.05). CONCLUSIONS: Even though there were no significant main effects of Cr diet treatment, DOX administration and no interactions, a potential trend indicated that the Cr loading protocol may prevent apoptosis by attenuating the expressions of cyt c and casp-9 in skeletal muscles. Further research with measuring oxidative stress level, protein synthesis and degradation, and amount of Cr supplementation consumed needs to be conducted in order to fully understand the mechanism of the Cr supplement and the DOX administrations in skeletal muscles.

Extent

80 pages

Local Identifiers

KimThesis2019

Rights Statement

Copyright is held by the author.

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