Lipidomics application to explain acute cardiotoxicity induced by doxorubicin
Doxorubicin (DOX) induced cardio-toxicity is one of the important limiting factors for the clinical use of this drug, the exact mechanism underlying the cardiotoxicity is still under debate and different experimental protocols were used. Lipidomics technology was used in this study to investigate the underlying
the cardiotoxicity is still under debate and different experimental protocols were used. Lipidomics technology was used in this study to investigate the underlying mechanism of cardiotoxicity induced by DOX. Lipidomics refers to the complete analysis of lipid profile of a cell or organism based on the principles and tools of analytical chemistry particularly mass spectrometry. This study was designed to investigate cardiotoxicity induced by doxorubicin using lipidomics technology.
Method: Twelve adult male rats divided randomly into two groups, each group comprising of six rats. 1: Control group (single dose (1ml) saline intraperitoneally); 2: DOX group (20 mg/ kg single dose intraperitoneally). After anesthesia, the myocardial tissue harvested and stored in liquid nitrogen, then the metabolites will be extracted from left ventricle of the heart tissue, derivatized using boron trifluride-methanol 10% and then the metabolites identified using GC-MS.
Results: The results showed that treatment with DOX produced significant (P<0.05) increase in the level of acetic acid, cholesterol, myristic acid, and stearic acid. Whereas the level of arachidonic acid, linolic acid, pentadecanoic acid, oleic acid and ricinoleic acid, decreased significantly (P<0.05) in DOX group. Lauric acid, palmitic acid, and methylcyclohexane, were found to be increased in DOX group.
Conclusion: This study showed that DOX induced cardiotoxicity can be identified by lipidomics technique by measuring lipid biomarkers of cardiotoxicity in heart tissue which include the saturated fatty acids (stearic acid, acetic acid and palmitic acid), unsaturated fatty acids (arachidonic acid, linoleic acid, and oleic acid) as well as cholesterol