Phosphorylation of GSK-3β and reduction of apoptosis as targets of troxerutin effect on reperfusion injury of diabetic myocardium.
Diabetes has various interactions with ischemic heart diseases. Troxerutin, a flavonoid, owns outstanding pharmacological potentials in cardiovascular medicine. The purpose of this study was to investigate the effects of troxerutin on phosphorylation of GSK-3β protein and apoptosis induced by myocardial ischemia-reperfusion injury in healthy and diabetic hearts. Male Wistar rats (n=36, 250-300 g) were randomly divided into four groups: healthy, diabetic, healthy-troxerutin and diabetic-troxerutin. Diabetes was induced by a single injection of streptozotocin (50 mg/kg; ip) and the diabetic period was lasted for ten weeks. Six weeks after induction of diabetes, troxerutin-treated groups received 150 mg/kg/day troxerutin by oral gavage for 4 weeks. The rats' hearts were transferred to the Langendorff apparatus and then subjected to 30 min regional ischemia followed by 45 min reperfusion. Supernatants of the left ventricle were used to measure the levels of cardiac troponin-I (cTnI) by ELISA, total and phosphorylated form of GSK-3β by western blotting and tissue apoptosis by TUNEL assay. Troxerutin administration significantly decreased the cTnI levels in healthy and diabetic groups, as compared to the corresponding controls (P<0.05). In addition, troxerutin significantly increased the level of phosphorylated form and the ratio of phosphorylated to total form of GSK-3β in diabetic and control groups (P<0.05). Tissue apoptosis level and apoptotic index also showed a significant decrease after administration of troxerutin in control and diabetic groups (P<0.05). The findings indicated that the attenuation of GSK-3β activity and subsequent reduction of apoptosis by troxerutin play significant roles in its cardioprotection on reperfusion injuries.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Behnaz
B
Mokhtari
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: badalzadehr@tbzmed.ac.ir.
Reza
R
Badalzadeh
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Alireza
A
Alihemmati
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Mustafa
M
Mohammadi
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006896:Hydroxyethylrutoside / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010477:Perfusion; D010766:Phosphorylation; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D016207:Cytokines; D006896:Hydroxyethylrutoside; C005865:troxerutin; C092073:cardiotrophin 1; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3
Diabetes; Ischemia–reperfusion injury; Ischemic heart disease; Troxerutin