Creatine Supplementation Mitigates Doxorubicin-Induced Skeletal Muscle Dysfunction but Not Cardiotoxicity

Area of Science:

• Biochemistry
• Muscle Physiology
• Toxicology

Background:

• Doxorubicin is a potent chemotherapy agent with known cardiotoxic and myotoxic side effects.
• Creatine is known for its role in energy metabolism and has demonstrated protective effects against muscle dysfunction.
• The specific protective capacity of creatine against doxorubicin-induced cardiac and skeletal muscle toxicity is not well-established.

Purpose of the Study:

• To investigate the potential protective effects of creatine supplementation against doxorubicin-induced cardiotoxicity and skeletal myotoxicity.
• To evaluate the impact of creatine on oxidative stress and inflammatory markers in response to doxorubicin treatment.

Main Methods:

• Twenty male C57BL/6J mice were divided into three groups: Control, Doxorubicin (Dox)-treated, and Doxorubicin plus Creatine (DoxCr)-treated.
• Doxorubicin was administered weekly, while the DoxCr group received concurrent creatine supplementation.
• Skeletal muscle atrophy, muscle strength, cardiac mass, cardiomyocyte diameter, oxidative stress markers (MDA, GSH/GSSG ratio), and IL-6 levels were assessed.

Main Results:

• Doxorubicin induced significant skeletal muscle atrophy in extensor digitorum longus and soleus muscles, reduced muscle strength, and increased oxidative stress and IL-6 levels.
• Cardiac toxicity was evidenced by reduced cardiac mass, decreased cardiomyocyte diameter, and elevated IL-6.
• Creatine supplementation mitigated doxorubicin-induced oxidative stress and prevented skeletal muscle atrophy and strength loss, but did not protect cardiac muscle.

Conclusions:

• Creatine supplementation demonstrates significant protective effects on skeletal muscle against doxorubicin-induced toxicity, including atrophy and strength reduction.
• Creatine does not appear to protect cardiac muscle from the toxic effects of doxorubicin.
• Further research is warranted to understand the differential effects of creatine on skeletal versus cardiac muscle in the context of chemotherapy-induced toxicity.