The master’s thesis entitled “Evaluation of the Possible Protective Effect of Ezetimibe against Doxorubicin-Induced Cardiotoxicity in Rats” was discussed for the researcher Aya Thaer Sabry and her supervisor Assistant Professor Dr. Mohammed Abdul-Hassan Jabarah, a faculty member of the College of Medicine / University of Baghdad, at the Pharmacology Department.
The study aimed to inspect the possible protective effect of two doses, 10 and 20 mg/kg, of Ezetimibe against Doxorubicin-induced cardiotoxicity in rats, and to investigate the mechanisms underlying Ezetimibe’s possible cardioprotective effect.
The study included twenty-four adult male Wistar rats that were allocated into four groups of six and treated as follows: Group I rats received corn oil orally for 14 consecutive days, Group II rats received 1 mL/kg corn oil orally for 14 consecutive days, and a single intraperitoneal injection of 15mg/kg Doxorubicin hydrochloride on the 12th day of the experiment, Group III rats received 10 mg/kg Ezetimibe orally for 14 consecutive days, and a single intraperitoneal injection of 15mg/kg Doxorubicin hydrochloride on the 12th day of the experiment, Group IV rats received 20 mg/kg Ezetimibe orally for 14 consecutive days, and a single intraperitoneal injection of 15mg/kg Doxorubicin hydrochloride on the 12th day of the experiment. After 24 hours from final administration, the experimental rats were anesthetized and blood samples were collected for biochemical analysis, after which the hearts were excised and heart tissue samples were obtained for biochemical and gene expression analyses.
The results showed that pretreatment with Ezetimibe at a dose of 10 or 20 mg/kg alleviated cardiac damage induced by Doxorubicin, as Ezetimibe blunted the rise in serum levels of cardiac troponin I and N-terminal pro-B-type natriuretic peptide. Additionally, pretreating rats with Ezetimibe at either dose mitigated Doxorubicin-induced oxidative stress by elevating the levels of superoxide dismutase and glutathione peroxidase, with consequent reduction in malondialdehyde in cardiac tissues. Furthermore, pretreatment with either dose of Ezetimibe hindered Doxorubicin-mediated inflammation, where Ezetimibe suppressed both cardiac nuclear factor-kappa B signaling and the gene expression of tumor necrosis factor-alpha with either dose and interleukin-1 beta with the higher one.
The study recommended that further researches utilizing a larger scale of animals and longer time intervals should be conducted. Also, to investigate whether Ezetimibe can improve cardiac function in case of Doxorubicin-induced cardiotoxicity in rats.
