The effects of n-methyl-d-aspartate receptor blockade on oxidative status in heart during conditioning maneuvers

© 2019, University of Kragujevac, Faculty of Science. All rights reserved. N-methyl-D-aspartate receptor (NMDAR) belongs to ionotropic glutamate receptor family. The most prominent roles of the NMDAR are related to the physiological and pathophysiological processes of the central nervous system (CNS). The link between NMDAR and cardiovascular pathology came into focus due to detrimental effects of homocysteine on the cardiovascular system. Regarding the fact that NMDAR affects Ca2+ homeostasis in cells, one of the main mechanisms which mediate adverse effects of glutamate dyshomeostasis and abnormal NMDAR activity is oxidative stress. Both in ischemia and during reperfusion, there are imbalance in Ca2+ and production of reactive species, which remains one of the basic mechanisms underlining the overall cardiomyocyte death due to myocardial infarction. The aim of this study was to assess the effects of blockade of NMDAR in heart using MK-801, in preconditioning and postconditioning fashion and to compare the values of oxidative stress biomarkers. We used Langendorff technique of isolated heart. In the control group, all isolated rat hearts were subjected to global ischemia after stabilization period (perfusion of the whole heart with Krebs-Henseleit solution was stopped) for 20 minutes, followed by 30 minutes of reperfusion. In the preconditioning group, after stabilization period, hearts were perfused with MK-801 for 5 minutes, before global ischemia of 20 minutes which was followed by 30 minutes reperfusion. In the postconditioning group, hearts were perfused with MK-801 during the first 3 minutes of reperfusion. Results of this study showed antioxidative effects of NMDAR inhibition in pre-and postconditioning of the isolated rat heart

Pituitary hyperplasia, hormonal changes and prolactinoma development in males exposed to estrogens—an insight from translational studies

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Estrogen signaling plays an important role in pituitary development and function. In sensitive rat or mice strains of both sexes, estrogen treatments promote lactotropic cell proliferation and induce the formation of pituitary adenomas (dominantly prolactin or growth-hormone-secreting ones). In male patients receiving estrogen, treatment does not necessarily result in pituitary hyperplasia, hyperprolactinemia or adenoma development. In this review, we comprehensively analyze the mechanisms of estrogen action upon their application in male animal models comparing it with available data in human subjects. Sex-specific molecular targets of estrogen action in lactotropic (PRL) cells are highlighted in the context of their proliferative and secretory activity. In addition, putative effects of estradiol on the cellular/tumor microenvironment and the contribution of postnatal pituitary progenitor/stem cells and transdifferentiation processes to prolactinoma development have been analyzed. Finally, estrogen-induced morphological and hormone-secreting changes in pituitary thyrotropic (TSH) and adrenocorticotropic (ACTH) cells are discussed, as well as the putative role of the thyroid and/or glucocorticoid hormones in prolactinoma development, based on the current scarce literature

Cathepsin D—Managing the Delicate Balance

Lysosomal proteases play a crucial role in maintaining cell homeostasis. Human cathepsin D manages protein turnover degrading misfolded and aggregated proteins and favors apoptosis in the case of proteostasis disruption. However, when cathepsin D regulation is affected, it can contribute to numerous disorders. The down-regulation of human cathepsin D is associated with neurodegenerative disorders, such as neuronal ceroid lipofuscinosis. On the other hand, its excessive levels outside lysosomes and the cell membrane lead to tumor growth, migration, invasion and angiogenesis. Therefore, targeting cathepsin D could provide significant diagnostic benefits and new avenues of therapy. Herein, we provide a brief overview of cathepsin D structure, regulation, function, and its role in the progression of many diseases and the therapeutic potentialities of natural and synthetic inhibitors and activators of this protease

Garlic Derived Diallyl Trisulfide in Experimental Metabolic Syndrome: Metabolic Effects and Cardioprotective Role

This study aimed to examine the effects of diallyl trisulfide (DATS), the most potent polysulfide derived from garlic, on metabolic syndrome and myocardial function in rats with metabolic syndrome (MetS). For that purpose, we used 36 male Wistar albino rats divided into control rats, rats with MetS and MetS rats treated with 40 mg/kg of DATS every second day for 3 weeks. In the first part, we studied the impact of DATS on MetS control and found that DATS significantly raised H2S, decreased homocysteine and glucose levels and enhanced lipid and antioxidative, while reducing prooxidative parameters. Additionally, this polysulfide improved cardiac function. In the second part, we investigated the impact of DATS on ex vivo induced ischemia/reperfusion (I/R) heart injury and found that DATS consumption significantly improved cardiodynamic parameters and prevented oxidative and histo-architectural variation in the heart. In addition, DATS significantly increased relative gene expression of eNOS, SOD-1 and -2, Bcl-2 and decreased relative gene expression of NF-κB, IL-17A, Bax, and caspases-3 and -9. Taken together, the data show that DATS can effectively mitigate MetS and have protective effects against ex vivo induced myocardial I/R injury in MetS rat