Role of endogenous oxytocin in cardiac ischemic preconditioning

Background: The aim of the present study is to assess the role of endogenous oxytocin (OT) in cardioprotective effects of ischemic preconditioning (IPC) in anesthetized rat. Materials and methods: Animals were divided into five groups: 1) ischemia-reperfusion (IR); (n= 6), hearts were subjected to 25 min regional ischemia and 60 min reperfusion, 2) OT; (n= 6), oxytocin was administered (0.03. μg/kg i.p) 10 min prior to ischemia, 3) IPC; (n= 7), IPC was induced via a 5 min regional ischemia followed by 5 min of reperfusion before IR, 4) IPC. +. ATO (Atosiban); (n= 6), atosiban (1.5. μg/kg i.p) was used as OT receptor selective antagonist in the beginning of IPC and 5) IR. +. ATO; (n= 6), atosiban was injected 10 min prior to ischemia-reperfusion. Results: In our experiment, Infarct size was decreased significantly in OT and IPC groups compared to IR (23 ± 1.5% and 19 ± 0.6% vs 45 ± 2.9% in IR group, P < 0.05). Administration of atosiban in IPC. +. ATO group increased infarct size to 39 ± 0.9% in comparison with OT and IPC groups (P<0.05). The use of OT and IPC prior to ischemia significantly declined ventricular arrhythmias severity in compared to IR group (1.2±0.4 and 1 ±0.5 respectively, vs 4±0.4 in IR group, P<0.05). Blockade of OT receptor by atosiban abolished the cardiopreconditioning effects of IPC. Conclusion: This study shows that, in part, the cardioprotective effects of IPC can be induced by endogenous OT. © 2010 Elsevier B.V

Oxytocin protects rat heart against ischemia-reperfusion injury via pathway involving mitochondrial ATP-dependent potassium channel

Cardiac preconditioning represents the most potent and consistently reproducible method of rescuing heart tissue from undergoing irreversible ischemic damage. One of the major goals of the current cardiovascular research is to identify a reliable cardioprotective intervention that can salvage ischemic myocardium. The aim of the present study is to evaluate the oxytocin (OT)-induced cardioprotection and the signaling pathway involved with mitochondrial ATP-dependent potassium (mitoKATP) channel in the anesthetized rat heart. Animals were divided into six groups (n = 6): (1) IR; hearts were subjected to 25 min ischemia and 120 min reperfusion, (2) OT; oxytocin was administered (0.03 μg/kg i.p.) 25 min prior to ischemia, (3) ATO+OT; atosiban (ATO) was used as an OT-selective receptor antagonist (1.5 μg/kg i.p.) 10 min prior to OT administration, (4) ATO; atosiban was used 35 min prior to ischemia, (5) 5HD + OT; 5-hydroxydecanoic acid (5HD) was used as a specific inhibitor of mitoKATP channel (10 mg/kg i.v.) 10 min prior to OT administration, (6) 5HD; 5HD was used 35 min prior to ischemia. Then infarct size, ventricular arrhythmia and creatine kinase-MB isoenzyme (CK-MB) plasma level were measured. Hemodynamic parameters were recorded throughout the experiment. OT administration significantly decreased infarct size, CK-MB plasma level, severity and incidence of ventricular arrhythmia as compared to IR group. Administration of atosiban and 5HD abolished the cardiopreconditioning effect of OT. This study demonstrates that cardioprotective effects of OT are mediated through opening the mitoKATP channels. © 2010 Elsevier Inc. All rights reserved

Hepatoprotective effect of Acantholimon bracteatum (Girard) Boiss. on formaldehyde-induced liver injury in adult male mice

Background and objectives: Acantholimon bracteatum (Girard) Boiss (Plumbaginaceae) is used in variety of diseases including hepatic ailments in the west regions of Iran. In the present study, the hepatoprotective effect of the methanol extract (ME) of A. bracteatum on formaldehyde (FA) induced liver injury has been investigated in adult male mice. Methods: Fifty six adult male mice were divided into 8 groups. The control group received normal saline. Group II (E2) was treated with formaldehyde 10 mg/kg. Group III to VIII (E3-E8) were treated with both FA (10 mg/kg) and the metanol extract at doses of 5, 10, 15, 20, 50 and 100 mg/kg, respectively. All animals were treated for 2 weeks (once every other day). At the end of the morphology, histopathology of liver and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were evaluated. Results: Formaldehyde induced liver damage both in histology and function. The levels of ALT, AST and ALP enzymes had significantly increased in FA treated group. Administration of ME in all experimental groups significantly reduced serum levels of ALP (p= 0.02); however, AST was reduced significantly just in groups III (E3) and IV(E5) (

Oxytocin protects cardiomyocytes from apoptosis induced by ischemia-reperfusion in rat heart: Role of mitochondrial ATP-dependent potassium channel and permeability transition pore

The current study examines the protective effect of oxytocin (OT) on cardiomyocyte apoptosis modulated by mitochondrial ATP-dependent potassium (mitoKATP) channel and permeability transition pore (mPTP) in the preconditioned myocardium of anesthetized rats. Eighty rats were equally divided into eight groups. The hearts of all animals except for the sham group were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin, 5-hydroxydeconoate (5-HD), a specific inhibitor of the mitoKATP channel, and atractyloside (ATRC), an mPTP opener, were used prior to ischemia. Hemodynamic parameters were recorded throughout the experiment. Evaluations were made by infarct size, plasma lactate dehydrogenase level (LDH), transmission electron microscopy (TEM) and immunohistochemistry studies. OT prevented mean arterial pressure drop during early phase of ischemia and reperfusion. Treatment with OT before IR induction normalizes cardiomyocytes both in light microscopy and TEM observations. In addition, OT significantly reduced TUNEL- and increased Bcl-2-labeled positive cell number relative to IR (p < 0.05). However, 5HD or ATRC inhibited the protective effects of OT on cardiomyocytes damaged by IR (p < 0.05). Ultrastructural changes including extensive myofibril loss, sarcolemmal disruption and mitochondrial swelling due to amorphous dens bodies indicate necrosis induction in 5HD and ATRC as well as in IR groups. Restoration of immunohistochemistry parameters and protection against IR-induced ultrastructural changes confirm OT cardioprotective effects via mitoKATP channel and mPTP modulation in apoptosis induced by ischemia-reperfusion. © 2012 Elsevier Inc