Effects of Apocynin, a NADPH Oxidase Inhibitor, in the Protection of the Heart from Ischemia/Reperfusion Injury

Mohammad, Ali; Babiker, Fawzi; Al‐Bader, Maie

doi:10.3390/ph16040492

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…For this, we isolated rat hearts and mounted them in a Langendorff perfusion system, as previously described [51]. We used the perfusion of apocynin as a reference cardioprotective agent, as it has been recently reported [57]. As can be observed in Figure 10A, during the baseline period of perfusion (min 0-15), neither of the compounds altered the perfusion pressure or cardiac rhythm (not shown).…”

Section: Molecular Docking Of C6 and C14 With P47 Phoxmentioning

confidence: 96%

New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22phox-p47phox Interactions

Treuer,

Faúndez,

Ebensperger

et al. 2023

Antioxidants

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NADPH oxidase (NOX2) is responsible for reactive oxygen species (ROS) production in neutrophils and has been recognized as a key mediator in inflammatory and cardiovascular pathologies. Nevertheless, there is a lack of specific NOX2 pharmacological inhibitors. In medicinal chemistry, heterocyclic compounds are essential scaffolds for drug design, and among them, indole is a very versatile pharmacophore. We tested the hypothesis that indole heteroaryl-acrylonitrile derivatives may serve as NOX2 inhibitors by evaluating the capacity of 19 of these molecules to inhibit NOX2-derived ROS production in human neutrophils (HL-60 cells). Of these compounds, C6 and C14 exhibited concentration-dependent inhibition of NOX2 (IC50~1 µM). These molecules also reduced NOX2-derived oxidative stress in cardiomyocytes and prevented cardiac damage induced by ischemia-reperfusion. Compound C6 significantly reduced the membrane translocation of p47phox, a cytosolic subunit that is required for NOX2 activation. Molecular docking analyses of the binding modes of these molecules with p47phox indicated that C6 and C14 interact with specific residues in the inner part of the groove of p47phox, the binding cavity for p22phox. This combination of methods showed that novel indole heteroaryl acrylonitriles represent interesting lead compounds for developing specific and potent NOX2 inhibitors.

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Section: Molecular Docking Of C6 and C14 With P47 Phoxmentioning

confidence: 96%

New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22phox-p47phox Interactions

Treuer,

Faúndez,

Ebensperger

et al. 2023

Antioxidants

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show abstract

“…Table I is a summary of the most recently published work showing the role of NAD + in cardiac health. The main NAD synthesizing regulators in the salvage pathway are also highly studied to understand the actual role of NAMPT, NAPRT, or NRK [ 19 – 35 ].…”

Section: Association Of Nad + With Cardiac Healthmentioning

confidence: 99%

The role of nicotinamide adenine dinucleotide salvage enzymes in cardioprotection

Kibria,

Das,

Arefin

2024

kitp

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The increasing trend of cardiac diseases is becoming a major threat globally. Cardiac activities are based on integrated action potential through electronic flux changes within intra- and extracellular molecular activities. Nicotinamide adenine dinucleotide (NAD) is a major electron carrier present in almost all living cells and creates gated potential by electron exchange from one chemical to another in terms of oxidation (NAD + ) and reduction (NADH) reactions. NAD + plays an important role directly or indirectly in protecting against various cardiovascular diseases, including heart failure, occlusion, ischemia-reperfusion (IR) injury, arrhythmia, myocardial infarction (MI), rhythmic disorder, and a higher order of cardiovascular complexity. Nicotinamide phosphoribosyl transferase (NAMPT) is well known as a rate-limiting enzyme in this pathway except for de-novo NAD synthesis and directly involved in the cardioprotective activity. There are two more enzymes – nicotinate phosphoribosyl transferase (NAPRT) and nicotinamide riboside kinase (NRK) – which also work as rate-limiting factors in the NAD+ synthesis pathway. This study concentrated on the role of NAMPT, NAPRT, and NRK in cardioprotective activity and prospective cardiac health.

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“…Most molecules used in pharmacological interventions have been reported to act on the RISK pathway by activating several signaling molecules [28]. Cyclosporin A (mPTP blocker), NO donor (SNAP), PKC activator (DOG), and mitoK ATP channel opener (CRK) were proven to be protective to the heart from I/R injury [29][30][31]. Therefore, in this study, we aimed to investigate the possible protection of the diabetic heart by reviving molecules from the RISK pathway that are probably inactivated by hyperglycemia.…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide/Glucose Transporter Type 4 Pathway Mediates Cardioprotection against Ischemia/Reperfusion Injury under Hyperglycemic and Diabetic Conditions in Rats

Al-Kouh,

Babiker

2024

J Vasc Res

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Introduction: The comorbidities of ischemic heart disease (IHD) and diabetes mellitus (DM) compromise the protection of the diabetic heart from ischemia/reperfusion (I/R) injury. We hypothesized that manipulation of reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways might protect the diabetic heart, and intervention of these pathways could be a new avenue for potentially protecting the diabetic heart. Methods: All hearts were subjected to 30-min ischemia and 30-min reperfusion. During reperfusion, hearts were exposed to molecules proven to protect the heart from I/R injury. The hemodynamic data were collected using suitable software. The infarct size, troponin T levels, and protein levels in hearts were evaluated. Results: Both cyclosporine-A and nitric oxide donor (SNAP) infusion at reperfusion protected 4-week diabetic hearts from I/R injury. However, 6-week diabetic hearts were protected only by SNAP, but not cyclosporin-A. These treatments significantly (p < 0.05) improved cardiac hemodynamics and decreased infarct size. Conclusions: The administration of SNAP to diabetic hearts protected both 4- and 6-week diabetic hearts; however, cyclosporine-A protected only the 4-week diabetic hearts. The eNOS/GLUT-4 pathway executed the SNAP-mediated cardioprotection.

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Effects of Apocynin, a NADPH Oxidase Inhibitor, in the Protection of the Heart from Ischemia/Reperfusion Injury

Cited by 4 publications

References 56 publications

New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22phox-p47phox Interactions

New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22phox-p47phox Interactions

The role of nicotinamide adenine dinucleotide salvage enzymes in cardioprotection

Nitric Oxide/Glucose Transporter Type 4 Pathway Mediates Cardioprotection against Ischemia/Reperfusion Injury under Hyperglycemic and Diabetic Conditions in Rats

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