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Role of Creatine Supplementation in Alleviating Hepatotoxicity Caused by Doxorubicin
Author(s) -
Aljobaily Nouf A.,
Viereckl Michael,
Aljobaily Hend A.,
Albertson Jammie A.,
Han Yuyan,
Hydock David
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06416
Subject(s) - sirius red , doxorubicin , creatine , medicine , h&e stain , fibrosis , oxidative stress , pharmacology , endocrinology , creatine kinase , immunohistochemistry , chemotherapy
Background and aim Doxorubicin is a chemotherapeutic agent that is widely used for several malignancies. It is known to have severe side effects such as hepatotoxicity, cardiotoxicity and increase in nitric oxide concentrations in skeletal muscles. On the other hand, creatine monohydrate is a supplementation used as a therapeutic agent and plays a significant role as regenerative agent. So far, there is not enough information about the effect of doxorubicin on the overall liver functionality and how creatine monohydrate helps in easing the hepatotoxicity; therefore, our aim is to investigate the role of creatine monohydrate supplementation in alleviating the hepatotoxicity caused by doxorubicin. Methods Sprague‐Dawley rats were fed rodent chow, 2% creatine, 4% followed by 2% creatine supplementation for our weeks; and 15 mg/kg doxorubicin was given once the day before they were sacrificed. Peripheral blood and liver were harvested and snap frozen. Serum chemistry was obtained to evaluate the liver function by looking at the levels of Lipemia, T‐Bilirubin, AST, ALP and ALT. Liver damage was evaluated by using Hematoxylin and Eosin staining; whereas liver fibrosis was evaluated by Sirius Red staining. RT‐PCR was performed to assess the gene expression of fibrotic genes, proliferative genes, oxidative stress and apoptosis‐related genes at the transcription level, and western blotting was performed to measure the gene expression at the protein level. Results There was no significant difference found in the serum chemistry in the treatment groups when compared to the control group. However, the histology showed an increase in inflammation and fibrosis in the doxorubicin group when compared to the control, where there was a decrease observed in the group treated with 4% creatine followed by 2% creatine. A significant increase in the gene expression of Bax, CK‐19 and Col1‐a1 has been observed in the 2% creatine + doxorubicin. Further, there was a decrease in the protein expression of CASP3 in the 2% creatine + doxorubicin and 4%/2% creatine + doxorubicin when compared to the doxorubicin group. Conclusion Based on the collected data and observed behavior of groups, we conclude that the gradual dose of creatine monohydrate supplementation does alleviate the hepatotoxicity caused by doxorubicin. Support or Funding Information Graduate Student Association at the University of Northern Colorado