Unit:
Κατεύθυνση Σχεδιασμός και Ανάπτυξη νέων Φαρμακευτικών Ενώσεων - ΦαρμακολογίαLibrary of the School of Science
Author:
Markou Laoutselnta
Supervisors info:
Ανδρεάδου Ιωάννα, Αναπληρώτρια Καθηγήτρια, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών, Σχολή Θετικών Επιστημών, Τμήμα Φαρμακευτικής
Original Title:
Μεταβονομική ανάλυση της δράσης της λεβοσιμεντάνης στην προκαλούμενη από δοξορουβικίνη καρδιοτοξικότητα
Translated title:
Metabolic analysis of the effect of levosimendan on doxorubicin-induced cardiotoxicity
Summary:
Doxorubicin (DXR), a cytotoxic antibiotic used in the treatment of various cancers, can cause progressive left ventricular dysfunction causing cardiomyopathy that eventually leads to irreversible congestive heart failure. Levosimendan (LEVO) is an innovative drug that combines positive inotropic and vasodilator action and improves cardiac function without significant changes in myocardial oxygen consumption.
In order to determine the effect of levosimendan on doxorubicin-induced cardiotoxicity, a left ventricular myocardial analysis was performed in 30 rats. The rats were divided into 4 groups. The control group was administered 10mL / kg i.p saline. The other three groups received DXR in consecutive doses, while two of the three were given levosimendan either in consecutive doses or in single doses. More specifically, in the groups receiving doxorubicin, this was administered at a total dose of 18 mg / kg ip divided into 6 doses, while in the two groups of levosimendan, the drug was administered at a total dose of 24 μg / kg ip given in 4 doses in one group and once in the other group. All rats underwent left ventricular echocardiography and then the animals were sacrificed and the left ventricle of the myocardium was taken for further analysis. This was followed by extraction and isolation of the polar phase, in which the analysis of the metabolic profile was performed with the help of Nuclear Magnetic Resonance.
The results showed that levosimendan alters energy metabolites but fails to inhibit doxorubicin-induced anaerobic metabolism. Single-dose administration of levosimendan appears to have better results in improving cardiotoxicity than sequential administration. Finally, levosimendan appears to induce rescue pathways associated with nicotinamide and impair purine metabolism.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
levosimendan, doxorubicin, cardiotoxicity, metabonomics, inotropy
Number of references:
107
