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Louw 2016 Abstract FASEB J

From Bioblast
Exercise limits loss of respiratory function seen with doxorubicin treatment without affecting muscle function.

Link: FASEB J Link

Louw MJ, Crandall AD, Murphy TS, Reynolds MS, Bernhisel D, Hancock CR (2016)


Doxorubicin (DOX) is a commonly-used chemotherapeutic drug with side effects including skeletal muscle wasting and weakness. It has been shown that DOX contributes to skeletal muscle damage through increasing oxidative stress. It is hypothesized that DOX interacts with free cellular iron to catalyze to the formation of reactive oxygen species (ROS). ROS contribute to cell damage and dysfunction, and thus may play a part in the skeletal muscle wasting seen with DOX treatment. Recent work has shown that exercise may help protect against this oxidative environment, thus preventing skeletal muscle wasting. We hypothesized that exercise would limit the loss of muscle function and respiration seen with DOX treatment. Male C57BL/6 mice were randomly placed into three groups: control, DOX, or EX+DOX. Control mice received five doses of saline orally for five days before sacrifice, and one dose of saline intraperitoneally three days before sacrifice. DOX mice received one dose of DOX at 15 mg/kg three days before sacrifice. EX+DOX mice were run for 60 min at ~20 m/sec for five consecutive days, then allowed to rest for two days. Mice then received a 15 mg/kg dose of DOX three days before sacrifice. Muscle function of the gastrocnemius platantaris soleus complex was measured in situ with mice under anesthesia (100 msec tetanic contractions at 0.5 Hz for 6 minutes). Mitochondrial respiratory function was measured in permeabilized fiber bundles from red gastrocnemius using high-resolution respirometry (Oroboros Oxygraph-2k). Treatment with DOX, with or without exercise, resulted in a 17.2% – 20.2% decrease in overall body weight compared to control (p-value < 0.001). Interestingly, the weight difference between DOX and EX+DOX groups was not significant. Additionally, DOX treatment reduced respiratory capacity compared to control for complex I-stimulated, complex II-stimulated, and uncoupled (maximal) respiration (21.6% – 57.1% reduction from control levels, p-value < 0.001). EX+DOX limited the loss of respiratory function seen with DOX alone (i.e., uncoupled respiration was 78.4% of control, p-value = 0.15). Surprisingly, there were no significant differences in peak specific tension, twitch tension, half relaxation time, or muscle fatigue between any of the groups. Our findings indicate that while exercise may prevent loss in respiratory function in skeletal muscle, this may not result in differences in muscle function. More research is needed in this area to find treatment options for DOX-induced skeletal muscle dysfunction.

This abstract is from the Experimental Biology 2016 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

β€’ O2k-Network Lab: US UT Provo Hancock CR

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, Pharmacology;toxicology 

Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: ET  Pathway: N, S  HRR: Oxygraph-2k