Effect of NAD on recovery of adenine nucleotide pool, phosphorylation potential, and stimulation of apoptosis during late period of reperfusion damage to myocardium

Sukoyan, G. V.; Andriadze, N. A.; E, Guchua; Карсанов, Н. В.

doi:10.1007/s10517-005-0208-3

Cited by 10 publications

(15 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results indicated that phenylephrine (PE, 20 µM)-mediated activation of these promoters was significantly reduced by treatment of cells with NAD, thus again demonstrating the anti-hypertrophic potential of NAD [6,19,20]. Early, Sukoyan has shown that treatment with oxidized form of NAD (preparation of Nadcin  ) reversed ischemic-reperfusion injury of myocardium in experimental models [16][17][18] and Bokeria confirm these results in randomized controlled study in patients with unstable angina pectoris and bypass grafting [21]. After this Bruzzone [22], have provided evidence that exogenous NAD enters into cardiomyocytes via connexin 43 (Cx43) channels permeable to extracellular NAD, NAD treatment dramatically decrease astrocytes and neurocytes death induced by a genotoxic agents or ischemic and traumatic damage, markedly decrease autophagy in the brain transient ischemia in experiments.…”

Section: Discussionmentioning

confidence: 93%

“…The mortality in ISO-treated group was 16% and zero in control group. Twenty seven rabbits with CH were randomly assigned into follows groups relative to receive therapy: CH, control II-without therapy (receive physiological solution, n=10); main I-daily given orally lisinopril (inhibitor of angiotensin converting enzyme, in form of lisinopril-dihydrate, Sigma-Aldrich), 1,0 mg/kg body weight, in combination with nebivolol hydrochloride (a cardioselective beta 1-adrenoceptor blocker facilitating vascular release of nitric oxide (NO), 10 mg/kg per day given orally via gastric lavage for 10 days starting on day 7-th after chronic ISO-induced myocardial damage (n=12); and main II-receive 15 mg/kg body weight, of Nadcin  , first oxidized form NAD-containing drug with antiischemic and anti-inflammatory activities [16][17][18], manufacturing by "Biotechpharm GE", Georgia] (n=11). Treatment duration in both group was 10 days.…”

Section: Experimental Designmentioning

confidence: 99%

See 1 more Smart Citation

Hypertrophic and Inflammatory Markers in Isoproterenol-Induced CardiacHypertrophy and its Pharmacological Correction

Gv¹,

Sv²,

Nm³

et al. 2017

Cardiovasc Pharm Open Access

View full text Add to dashboard Cite

Keywords: Cardiac hypertrophy; Cerebral arteries; Experiment modeling; NAD; Redox-potential; Tumor necrosis factor alpha; Nuclear factor kappa B IntroductionOne consequence of excessive catecholamine stimulation is an increased β-adrenergic receptor kinase activity leading to uncoupling of the decreased left ventricular myocardial β-adrenoceptor population in failing myocardium. Together with an increase in inhibitory G-proteins, this results in a decreased inotropic responsiveness of the heart to catecholamines. Chronic increased sympathetic activation represents an important hallmark of induced maladaptive (pathologic) hypertrophy development, resulting in myocyte cell death, fibrosis, ventricular dilation, as independent cause of its transition to heart failure [1][2][3][4]. In cardiac hypertrophy (CH) and CHF, the G-dependent pathways activated by norepinephrine, as one of neurohormones, stimulate mitogen-activated protein kinases (MAPK); the elusive signaling pathway responsible for many cerebral and brain injury. Despite of that the common link between CH, endothelial dysfunction, MAPK activation and cerebrovascular events still speculative [5,6]. Several experimental and clinical data suggest that left ventricular (LV) hypertrophy is associated with cerebral damage even in the absence of clinical symptoms [2,3,7]. These hypertrophic stimuli affect the not only a mere response to the mechanical stress from elevated blood pressure, but also dysbalance in some factors (signaling small molecules) promoting the progression of LV pathological remodeling and vasoactive peptides releasing (such as norepinephrine, angiotensin II and endothelin-1), growth factors, oxidative stress markers, heat shock proteins, calcineurin, cytokines and some kinases. Although this diverse array of β-adrenergic stimulated interacting cascades was shown to induce cardiac remodeling, it is not determined yet AbstractBackgrounds: Short-term sustained beta-adrenergic stimulation is a hallmark of sympathetic hyperactivity and a common future in cardiovascular disease. Activation of endogenous cell signaling pathways that negatively regulate cardiac hypertrophy including the decline of NAD and the reduction of the intracellular NAD + /NADH ratio. The hypothesis that prevention of NAD depletion in myocardium may be critical in the treatment of cardiac hypertrophy and inflammatory responses was tested. Methods:On the 7 days of isoproterenol (ISO)-induced cardiac hypertrophy (CH) all animals were randomly assigned into 3 groups: control-without therapy (infusion of 0,9% NaCl); main I-receive 10 mg/kg nebivolol per os in combination with lisinopril infusion; and main II-receive infusion of 15 mg/kg of Nadcin  dissolved in water for injection. All animals were euthanized throughout 7 days after beginning of treatment. Results and conclusion:The increases of heart weight by 18,6% and heart-to-body weight ratio by 35,5% observed in ISO-induced CH were significantly suppressed in lisinopril-nebivolol therapy and monotherapy with NAD + -containi...

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Experimental Designmentioning

confidence: 99%

Hypertrophic and Inflammatory Markers in Isoproterenol-Induced CardiacHypertrophy and its Pharmacological Correction

Gv¹,

Sv²,

Nm³

et al. 2017

Cardiovasc Pharm Open Access

View full text Add to dashboard Cite

show abstract

“…The presurgery procedures and methods of assessing intracardiac hemodynamics and graduated stenosis of the coronary artery were described elsewhere [1,3]. Assays for ATP and PARP as well as the measurements of NAD/ NADH ratio in cardiomyocytes were performed according to [3,4]. The data were analyzed statistically using SPSS-10 software and Student's t test.…”

Section: Methodsmentioning

confidence: 99%

“…Inability of myocardial mitochondria to maintain the NAD/NADH ratio, to produce suffi cient amounts of ATP, and to maintain the water-electrolyte balance triggers the mechanisms of nonapoptotic cell death and the development of necrotic alterations in cardiomyocytes [5]. Consequently, our aim was to examine the possibility of arresting the onset of the processes leading to cardiomyocyte death with adenocine, β-acetyldigoxin, milrinone lactate, and levosimendan (a non-glycoside cardiotonic drug improving myocardial contractility without elevation of intracellular calcium [1][2][3][4]) during chronic HF.…”

mentioning

confidence: 99%

Mechanism of Cardioprotective Effect of Adenocine and Non-Glycoside Cardiotonic Drugs during Experimental Chronic Cardiac Insufficiency

Sukoyan

Gongadze

2011

Bull Exp Biol Med

Self Cite

View full text Add to dashboard Cite

The therapeutic action of adenocine during cardiac insufficiency (heart failure) caused by ischemic (stenosis) or reperfusion (removal of ligature) injury to the myocardium prevents depletion of ATP, the major energy source for myocytes in the right and left ventricles, and a drop in NAD/NADH ratio. The development of energy shortage during heart failure cannot be eliminated by β-acetyldigoxin, levosimendan, or milrinone: the content of ATP in the right and left ventricular myocardium remained below the normal level by 28 and 29%, 37 and 33%, 32 and 28%, respectively; the NAD/NADH ratio of the energy supply system in cardiomyocytes did not return to normal. Adenocine increased the content of NAD to the normal level in both the right and left ventricles, while it remained below the normal level after administration of β-acetyldigoxin (by 24 and 19.5%, respectively), levosimendan (by 27 and 29%), and milrinone (by 26 and 24%). In contrast to β-acetyldigoxin, levosimendan, and milrinone, adenocine inhibited activity of poly(ADP-ribose) polymerase in both ventricles. It is concluded that adenocine directly inhibits the key enzyme triggering apoptosis; we also hypothesized that this drug activates the regulatory and signal mechanisms arresting apoptotic alterations in the myocardium during heart failure.

show abstract

“…The technique of preoperative treatment, study of intracardiac hemodynamics, and method of coronary artery stenosis were described elsewhere [3]. The treated and control animals were killed on day 14 after coronary artery occlusion.…”

Section: Methodsmentioning

confidence: 99%

Effect of nadcin on energy supply system and apoptosis in ischemia-reperfusion injury to the myocardium

Sukoyan¹,

Kavadze²

2008

Bull Exp Biol Med

Self Cite

View full text Add to dashboard Cite

Nadcin in a dose of 90 mg/kg administered to dogs with subacute stage of ischemia-reperfusion myocardial injury immediately after blood flow resumption normalized redox potential of cardiomyocytes and mitochondria and restored the total content of adenyl and pyridine nucleotides. The decrease in the synthesis of ATP and pyridine nucleotides and reduction of the redox potential of the energy supply system were inversely related to the increase in poly-(ADP-ribose)-polymerase activity in the ischemic area and nonischemic region. Nadcin abolished the increase in poly-(ADP-ribose)-polymerase activity in the ischemic area of the right ventricle, nonischemic region, and ischemic area of the left ventricle (by 2.4, 2.9, and 1.52 times, respectively) and normalized bioenergetic activity of cardiomyocytes during ischemia-reperfusion myocardial injury.

show abstract

Effect of NAD on recovery of adenine nucleotide pool, phosphorylation potential, and stimulation of apoptosis during late period of reperfusion damage to myocardium

Cited by 10 publications

References 8 publications

Hypertrophic and Inflammatory Markers in Isoproterenol-Induced CardiacHypertrophy and its Pharmacological Correction

Hypertrophic and Inflammatory Markers in Isoproterenol-Induced CardiacHypertrophy and its Pharmacological Correction

Mechanism of Cardioprotective Effect of Adenocine and Non-Glycoside Cardiotonic Drugs during Experimental Chronic Cardiac Insufficiency

Effect of nadcin on energy supply system and apoptosis in ischemia-reperfusion injury to the myocardium

Contact Info

Product

Resources

About