Monoamine Oxidase-Related Vascular Oxidative Stress in Diseases Associated with Inflammatory Burden.

Monoamine oxidases (MAO) with 2 isoforms, A and B, located at the outer mitochondrial membrane are flavoenzyme membranes with a major role in the metabolism of monoaminergic neurotransmitters and biogenic amines in the central nervous system and peripheral tissues, respectively. In the process of oxidative deamination, aldehydes, hydrogen peroxide, and ammonia are constantly generated as potential deleterious by-products. While being systematically studied for decades as sources of reactive oxygen species in brain diseases, compelling evidence nowadays supports the role of MAO-related oxidative stress in cardiovascular and metabolic pathologies.

A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phytocompound.

Apigenin (4',5,7-trihydroxyflavone) (Api) is an important component of the human diet, being distributed in a wide number of fruits, vegetables and herbs with the most important sources being represented by chamomile, celery, celeriac and parsley. This study was designed for a comprehensive evaluation of Api as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound. In the set experimental conditions, Api presents antiproliferative activity against the A375 human melanoma cell line, a G2/M arrest of the cell cycle and cytotoxic events as revealed by the lactate dehydrogenase release.

Vitamin D improves vascular function and decreases monoamine oxidase A expression in experimental diabetes.

The active form of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)D), was reported to improve vascular function in patients with diabetes, yet the underlying mechanisms remain to be fully elucidated. Monoamine oxidase (MAO), a mitochondrial enzyme, with two isoforms (A and B) that generates hydrogen peroxide (HO) as by-product, has been recently reported to contribute to the pathogenesis of endothelial dysfunction in diabetes. The present study assessed the interaction between vitamin D and MAO in the vascular wall in the setting of type 1 experimental diabetes.

Monoamine oxidase inhibition improves vascular function and reduces oxidative stress in rats with lipopolysaccharide-induced inflammation.

Oxidative stress and vascular inflammation are the two major pathomechanisms that contribute to the progression of both cardiovascular and metabolic diseases. We have previously demonstrated that monoamine oxidases (MAOs), mitochondrial enzymes with two isoforms (A and B), are contributors to the endothelial dysfunction associated with inflammation in mice. The present study was purported to assess the effects of MAOs on endothelial dysfunction in rats with lipopolysaccharide (LPS)-induced acute inflammation.

Methylene blue alleviates endothelial dysfunction and reduces oxidative stress in aortas from diabetic rats.

Endothelial dysfunction and the related increase in reactive oxygen species (ROS) production are important events in the pathophysiology of diabetes mellitus (DM). Methylene blue (MB) has been systematically investigated for its protective effects against refractory hypotension and mitochondrial dysfunction. We have previously demonstrated that MB improved mitochondrial respiration and partially decreased oxidative stress in diabetic rat hearts.

Quercetin exerts an inhibitory effect on cellular bioenergetics of the B164A5 murine melanoma cell line.

Modulation of mitochondrial bioenergetics and glycolysis in malignancies has recently emerged a potential chemotherapeutic strategy since numerous malignant cells have overcome inhibition of the glycolytic pathway by increasing mitochondrial ATP production. Quercetin is a flavonoid with antioxidant, antiangiogenic, and chemoprotective properties but the mitochondrial effects are less characterized. The present study was purported to assess the effects of quercetin on the bioenergetic profile of B164A5 murine melanoma cell line.

Modulation of Cancer Metabolism by Phytochemicals - A Brief Overview.

Despite tremendous research efforts for effective therapies, cancer remains the plague of the century and its burden is expected to increase worldwide in the near future. Metabolic reprogramming is a firmly established hallmark of all cancers, regardless of their cellular or tissue origin, being a prerequisite for both tumor growth and invasion. Functional dependence of tumors on glycolysis and glutaminolysis and the crucial contribution of mitochondria to the tumor bioenergetic versatility are well recognized features and established therapeutic targets.

Contribution of monoamine oxidases to vascular oxidative stress in patients with end-stage renal disease requiring hemodialysis.

Arteriovenous fistula (AVF) is the "lifeline" for patients with end-stage renal disease (ESRD) undergoing hemodialysis. AVF maturation failure is a poorly understood process, one of the contributors being endothelial dysfunction due to oxidative stress. Monoamine oxidases (MAOs) A and B were recently identified as novel sources of vascular oxidative stress.

Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts.

Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox drug with reported protective effects mainly on brain mitochondria. The purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, HO production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats.

The effect of purinergic signaling via the PY receptor on vascular function in a rat model of acute inflammation.

There is a growing body of evidence pointing to the role of purinergic signaling in the development and progression of various conditions that have inflammation as a common pathogenetic denominator. The aim of the present study was to assess the involvement of PY purinergic receptors in the regulation of vascular function in aortic segments obtained using an experimental model of acute inflammation, the lipopolysaccharide (LPS, 8 mg/kg, i.p)-treated rats.

Monoamine oxidase inhibition improves vascular function in mammary arteries from nondiabetic and diabetic patients with coronary heart disease.

Monoamine oxidases (MAOs) are mitochondrial enzymes with 2 isoforms that have emerged as important contributors to cardiovascular oxidative stress via the constant generation of hydrogen peroxide. The present study was purported to assess whether MAO-derived HO contributes to the endothelial dysfunction in mammary arteries harvested from coronary heart disease patients with and without diabetes mellitus subjected to coronary artery bypass grafting. To this aim, the effects of MAO inhibition on vascular contractility to phenylephrine and endothelial-dependent relaxation (EDR) in response to acetylcholine were studied in vascular segments.

The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies.

Ischaemia/reperfusion (I/R) injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS).

Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues.

A substantial body of evidence indicates that pharmacological activation of mitochondrial ATP-sensitive potassium channels (mKATP) in the heart is protective in conditions associated with ischemia/reperfusion injury. Several mechanisms have been postulated to be responsible for cardioprotection, including the modulation of mitochondrial respiratory function. The aim of the present study was to characterize the dose-dependent effects of novel synthetic benzopyran analogues, derived from a BMS-191095, a selective mKATP opener, on mitochondrial respiration and reactive oxygen species (ROS) production in isolated rat heart mitochondria.

Acute inhibition of monoamine oxidase and ischemic preconditioning in isolated rat hearts: interference with postischemic functional recovery but no effect on infarct size reduction.

Monoamine oxidases (MAOs) have recently emerged as important mitochondrial sources of oxidative stress in the cardiovascular system. Generation of reactive oxygen species during the brief episodes of ischemic preconditioning (IPC) is responsible for the cardioprotection at reperfusion. The aim of this study was to assess the effects of two MAO inhibitors (clorgyline and pargyline) on the IPC-related protection in isolated rat hearts.

BIOENERGETIC CHARACTERIZATION OF H9C2 CELLS USING THE EXTRACELLULAR FLUX ANALYZER.

Unlabelled: The aim of the present work was to standardize the working methodology for assessing the bioenergetic profile of H9c2 cardiomyoblasts cells, with reference to the optimization of cell seeding number and the establishment of favorable concentrations for the classic modulators of mitochondrial respiratory function, in particular the one of a classical uncoupler, FCCP.

Material And Methods: The extracellular flux analyzer (XF, Seahorse Bioscience) is a novel high-throughput instrument able to monitor the metabolism of living cells by simultaneously measuring mitochondrial respiration and glycolysis. The in vitro platform will be further used to better understand the pathophysiology and the unrecognized side effects of drugs currently used in the therapy of major cardiovascular diseases.

Monoamine Oxidases as Potential Contributors to Oxidative Stress in Diabetes: Time for a Study in Patients Undergoing Heart Surgery.

Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs) at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction.

Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes.

Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters.

Betulinic acid as a potent and complex antitumor phytochemical: a minireview.

Betulinic acid (BA), a natural compound with a lupan skeleton, has been highly investigated in the past decade for a plethora of beneficial properties, including anti-cancer, anti-inflammatory, anti-angiogenic, immune-modulatory, and anti-HIV effects. In particular, BA has been reported to be effective in vitro against tumor cell lines of different origins, and also in vivo, in animal models of cancer. The best characterized mechanism of its antitumor effect consists of triggering apoptosis via the mitochondrial pathway.

Monoamine oxidase--a inhibition reverses endothelial dysfunction in hypertensive rat aortic rings.

Aim: Monoamine oxidases (MAOs) are mitochondrial enzymes, with 2 isoforms, A and B that convert biogenic amines to their corresponding aldehydes via a reaction that produces hydrogen peroxide. Since MAO-A is the predominant form at vascular level we hypothesized that MAO-A-dependent H2O2 production may contribute to the development of endothelial dysfunction and, MAOs inhibition could improve the vascular function, respectively.

Material And Methods: To this aim aortic rings were isolated from female adult spontaneously hypertensive rats (SHR) and their corresponding (Wistar-Kyoto) controls.

Morphological and functional aspects of sciatic nerve regeneration after crush injury.

Experimental models for the investigation of nerve regeneration are critical in studying new strategies able to promote the repair process. The aim of the present work was to characterize morphological and functional aspects of sciatic nerve regeneration after mechanical crush injury in rodents. Morphological changes were assessed after a four minutes sciatic nerve injury induced by means of a standardized compression clip.

Activation of prosurvival signaling pathways during the memory phase of volatile anesthetic preconditioning in human myocardium: a pilot study.

According to a compelling body of evidence anesthetic preconditioning (APC) attenuates the deleterious consequences of ischemia-reperfusion and protects the heart through a mechanism similar to ischemic preconditioning. The present study was purported to investigate the intracellular signaling pathways activated in human myocardium in response to a preconditioning protocol with two different volatile anesthetics, namely isoflurane and sevoflurane. To this aim, phosphorylation of PKCα and -δ, ERK1/2, Akt, and GSK3β was determined at the end of the APC protocol, in human atrial samples harvested from patients undergoing open-heart surgery.

Ageing-induced decrease in cardiac mitochondrial function in healthy rats.

It is widely recognized that mitochondrial dysfunction is a key component of the multifactorial process of ageing. The effects of age on individual components of mitochondrial function vary across species and strains. In this study we investigated the oxygen consumption, the mitochondrial membrane potential (Δψ), the sensitivity of mitochondrial permeability transition pore (mPTP) to calcium overload, and the production of reactive oxygen species (ROS) in heart mitochondria isolated from old compared with adult healthy Sprague-Dawley rats.

Cardioprotection against myocardial reperfusion injury: successes, failures, and perspectives.

The past few decades have witnessed an enormous number of research strategies aimed at protecting the heart against myocardial ischemia-reperfusion injury. Several randomized clinical trials are nowadays in progress testing whether promising therapeutic strategies aimed at preventing lethal reperfusion injury can be translated from bench to bedside. Many of these interventions, either pharmacological or mechanical, are targeting mitochondria as the final effectors of cardioprotection.

Substrate-specific impairment of mitochondrial respiration in permeabilized fibers from patients with coronary heart disease versus valvular disease.

High-resolution respirometry of permeabilized myocardial fibers offers reliable insights concerning the integrated mitochondrial function while using small amounts of cardiac tissue. The aim of the present study was to assess the respiratory function in permeabilized fibers of human right atrial appendages harvested from patients with coronary heart disease (CHD) (n = 6) versus patients with valvular disease (n = 5) and preserved ejection fraction that underwent non-emergency cardiac surgery. Human bundle samples (1-3 mg wet weight) permeabilized with saponin were transferred into the 2 ml Oxygraph-2 k chambers to measure complex I(CI) and II (CII)-dependent respiration, respectively.