Liraglutide ameliorates cardiotoxicity induced by doxorubicin in rats through the Akt/GSK-3β signaling pathway.
Doxorubicin (Dox)-induced cardiotoxicity constitutes the major adverse effect that limited its use. We investigated the possible protective effects of liraglutide on Dox-induced cardiotoxicity in rats. Rats were divided into the following groups: control group rats received normal saline [1 ml/kg, intraperitoneal (i.p.)]; doxorubicin group rats received doxorubicin (1.25 mg/kg, i.p.), four times per week for 4 weeks; and liraglutide group rats received doxorubicin (1.25 mg/kg, i.p.) four times per week for 4 weeks then received liraglutide (100 μg/kg, i.p) daily for 4 weeks. At the end of the study, animals were sacrificed and serum creatine kinase-MB (CK-MB) and troponin I levels were determined. Malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and caspase-3 levels of the heart were determined. Cardiac AMPK, phosphorylated-Akt, tissue growth factor-β1 (TGF-β1), and GSK3-β levels of the heart were determined. Hematoxylin and eosin (H&E) stained sections form the heart were examined as well as immunohistochemical sections for detection of Bcl-2 expression. Dox treatment increased serum level of troponin I and CK-MB while decreased SOD activity, decreased AMPK, and p-Akt cardiac levels with increased in MDA, IL-6, TNF-α,GSK-3b, TGFB1, and caspase-3 levels in the heart with inflammation and necrosis in cardiac histopathology with decreased Bcl-2. Treatment with liraglutide decreased troponin I and CK-MB while increased SOD activity, AMPK, p-Akt with decrements in MDA, IL-6, TNF-α, GSK-3β, TGF-β1, and caspase-3 levels with attenuation of inflammation and necrosis while increased Bcl-2 expression. Liraglutide may thus represent a new clinical tool for the treatment of Dox-induced cardiotoxicity.
['Abbas|Noha A T|NAT|', 'Kabil|Soad L|SL|']
D000818:Animals D000903:Antibiotics, Antineoplastic D002316:Cardiotonic Agents D066126:Cardiotoxicity D052279:Creatine Kinase, MB Form D004317:Doxorubicin D000071679:Glycogen Synthase Kinase 3 beta D007004:Hypoglycemic Agents D015850:Interleukin-6 D000069450:Liraglutide D008297:Male D008315:Malondialdehyde D009206:Myocardium D051057:Proto-Oncogene Proteins c-akt D017208:Rats, Wistar D015398:Signal Transduction D013482:Superoxide Dismutase D019210:Troponin I D014409:Tumor Necrosis Factor-alpha
Liraglutide Cardiotoxicity Doxorubicin Caspase-3 Apoptosis