Doxorubicin AKA “The red devil” is a commonly used chemotherapeutic drug. It induces significant oxidative injury at the cellular level and is routinely used for aggressive forms of cancer. Severe side effects of doxorubicin include cardiac and liver damage. Mitigating the severity of these side effects is an important part of ongoing research. It has the potential to improve patients’ lives and long-term life expectancy. Creatine is a considered a safe ergogenic substance and recently has been suggested as a potential therapeutic for doxorubicin induced side effects. To explore this potential benefit, Sprague-Dawley rats were used as a model organism. Six treatment groups consisting of four rats each received either saline, doxorubicin, 2% creatine/saline, 2%creatine/doxorubicin, 4/2%creatine/saline, 4/2% creatine/doxorubicin. The treatment groups were anesthetized and sacrificed after treatment. Liver samples were then collected. Tissue was snap frozen with liquid nitrogen. Liver function was examined by serum chemistry. Liver to body-weight ratio was calculated. H&E staining and Sirius red staining were used to examine the liver damage and liver fibrosis histologically. Genomic DNA and total RNA was also isolated and used to examine global methylation and apoptotic, liver fibrosis, oxidative, and inflammation biomarkers through ELISA and qPCR. The liver bodyweight ratio with the doxorubicin treatment presented significantly higher. 4/2% creatine/doxorubicin treatment recovered, while the 2% creatine/doxorubicin treatment significantly atrophied. Apoptosis, proliferation, and fibrosis increased in the 2% creatine/doxorubicin treatment while no significant increases occurred in the 4/2% creatine/doxorubicin treatments. Further, hypomethylation was shown in the doxorubicin treatment, while the 2% and 4/2% creatine/doxorubicin helped increase methylation levels. Together these results indicate a dose dependent effect of creatine supplementation with lower doses driving increased levels of stress and high doses improving liver phenotype. Our results indicate that overall liver health is improved as a result of creatine supplementation.
Viereckl, Michael; Alojibaily, Nouf; Hydock, David; and Han, Yuyan, "The Role of Creatine Supplementation in Alleviating Doxorubicin Induced Hepatotoxicity" (2020). 2020 Undergraduate Presentations. 42.