Effect of pre-treatment with oxytocin on cardiac enzymes in regional ischemia-reperfusion injury induced in the rat heart

Introduction: Cardiac preconditioning represents the most potent and consistently reproducible method of rescuing heart tissue from undergoing irreversible ischemic damage. The aim of the present study was to evaluate oxytocin (OT) induced cardioprotection and its signaling pathways on lactate dehydrogenase (LDH) and creatine kinase-MB isoenzyme (CK-MB) in the anesthetized rats. Methods: Eighty-four rats were divided into fourteen groups. Animal's hearts were subjected to 25 min ischemia and 2 h reperfusion (I/R). Oxytocin (0.03 μg/kg) was used 25 min prior to ischemia. Atosiban, an OT receptor antagonist (1.5 μg/kg), 5-hydroxydecanoic acid, an inhibitor of mitochondrial ATP-dependent potassium channel (10 mg/kg), atractyloside, an opener of mitochondrial permeability transition pores (5 mg/kg), chelytraine, a protein kinase C inhibitor (5 mg/kg) and N-acetylcysteine, a reactive oxygen species scavenger (200 mg/kg) were used 10 min prior to OT administration. Then, LDH and CK-MB levels in plasma were measured. Results: OT administration significantly decreased CK-MB and LDH levels compared to I/R group. Administration of atosiban, 5-hydroxydecanoic, atractyloside, chelytraine and N-acetylcysteine abolished the cardiac preconditioning effect of OT. Conclusion: The present study demonstrates that oxytocin cardioprotective effects are complex and its signaling pathways may mediate through mKATP channels, mPTP, PKC activation and increase ROS

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

Therapeutic effects of dendrosomal solanine on a metastatic breast tumor

Aims Our previous studies showed that alpha-solanine can inhibit tumor growth in cell culture and animal models of breast cancer. However, solanine is insoluble in common solvents; therefore, we developed a special nanoparticle with high-capacity solubility. The present study is aimed to deliberate the therapeutic effects of dendrosomal solanine (DNS) on a metastatic breast tumor in vitro and in vivo. Main methods After DNS preparation and dosing procedures, forty-five mice were equally divided into five groups to investigate the anti-metastatic effects of DNS on mammary tumor-bearing mice. Key findings Compared to solanine, DNS significantly suppressed the proliferation of 4 T1 cells in a dose- and time-dependent manner. DNS showed a remarkable safety rate of up to 10 mg/kg. A significant decrease in white blood-cell count was seen at 20 mg/kg DNS in comparison with control animals. Mice treated with DNS had smaller tumor volume (mm3) in comparison with control and solanine groups. Moreover, the incidence of the breast tumor metastases was about 67 in the control animals, where as solanine and DNS 1 mg/kg were about 22 and 0, respectively. Furthermore, the number of metastases per mouse varied from one to three. The tissues of tumor, brain, liver, spleen, and lung showed higher expression levels of Bcl-2 but lower expression levels of Bax, MMP-2, MMP-9, mTOR, and Akt in DNS-treated mice than control and solanine groups. Significance The findings suggest that DNS has a more impactful therapeutic effect than solanine on 4 T1-induced breast tumorigenesis via influencing the tissue microenvironment. © 2016 Elsevier Inc. All rights reserved

An innovative systematic approach introduced the involved lncRNA-miR-mRNA network in cell cycle and proliferation after conventional treatments in breast cancer patients

The present study aimed to explore the involved lncRNA-miRNA-mRNA network in the cell cycle and proliferation after conventional treatments in Luminal A breast cancer patients.The candidate miRNAs (miRs), lncRNAs, and mRNAs were first taken from the Gene Expression Omnibus and TCGA databases. The lncRNA�miR�mRNA network was then constructed using the high-throughput sequencing data. The expression levels of selected targets were measured in the breast cancer and healthy samples by the Real-Time PCR technique and compared with the clinical outcomes by the Kaplan-Meier method.Our analysis revealed a group of differentially expressed 3 lncRNAs, 9 miRs, and 14 mRNAs in breast cancer patients. A significant expression decrease of the selected tumor suppressor lncRNAs, miRs, and genes and a substantial expression increase of the selected onco-lncRNAs, oncomiRs, and oncogenes were obtained in the patients compared to the healthy group. The plasma levels of the lncRNAs, miRs, and mRNAs were more significant after the operation, chemotherapy, and radiotherapy than the pre-treatment. The Kaplan-Meier analysis indicated that the patients with a high expression of miR-21, miR-20b, IGF1R, and E2F2 and a low expression of miR-125a, PDCD4, and PTEN had exhibited a shorter overall survival rate.Our results suggested that the underlying mechanisms of the lncRNA, miRs, and mRNAs and relevant signaling pathways may be considered predictive and therapeutic targets for breast cancer. © 2022 Informa UK Limited, trading as Taylor & Francis Group