Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction])

Pasupathy, Sivabaskari; Tavella, Rosanna; Grover, Suchi; Raman, Betty; Procter, Nathan E.K.; Du, Yang; Mahadavan, Gnanadevan; Stafford, Irene; Heresztyn, Tamila; Holmes, Andrew S.; Zeitz, Chris; Arstall, Margaret; Selvanayagam, Joseph B.; Horowitz, John D.; Beltrame, John F.

doi:10.1161/circulationaha.117.027575

Cited by 119 publications

(82 citation statements)

References 53 publications

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“…16 Given that cardiac injury and thrombosis are well established as potentially lethal complications in COVID-19, it is noteworthy that intravenously administered NAC has been shown to potentiate the vasodilator, anti-inflammatory and antiaggregatory effects of nitroglycerin, and this useful interaction has been translated into improving outcomes, such as in acute myocardial infarction, unstable angina and acute pulmonary edema. 68,69 Administration of NAC has been included among the possible strategies aimed at preserving endothelial function and limiting microthrombosis in severe forms of COVID-19. 70 In case of severe COVID-19 forms with pulmonary and/or systemic symptoms, intravenously administered NAC at the high doses that are commonly used in case of paracetamol intoxication, given at the first onset of chest symptoms, would be expected to play an adjuvant therapeutic role in combination with antivirals or other drugs.…”

Section: Discussionmentioning

confidence: 99%

Rationale for the use of N ‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19

Balansky²,

2020

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COVID‐19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID‐19 patients. N‐ Acetyl‐L‐cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin‐converting enzyme 2 thereby hampering penetration of SARS‐CoV‐2 into cells. Based on a broad range of antioxidant and anti‐inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID‐19, as it was previously demonstrated for influenza and influenza‐like illnesses. Moreover, high‐dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID‐19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.

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Section: Discussionmentioning

confidence: 99%

Rationale for the use of N ‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19

Balansky²,

2020

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“…It has also been studied in a variety of other conditions such as psychiatric illnesses, cardiac diseases, and chronic lung disorders [87] [88] [89]. NAC’s antioxidant properties are related to its role as a precursor for glutathione, the main intracellular antioxidant responsible for free radical and ROS scavenging, buffering, and many other cellular reactions [90].…”

Section: Discussionmentioning

confidence: 99%

Metabolic coupling and the Reverse Warburg Effect in cancer: Implications for novel biomarker and anticancer agent development

Wilde

Roche

Domingo‐Vidal

et al. 2017

Seminars in Oncology

259

213

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Glucose is a key metabolite used by cancer cells to generate ATP, maintain redox state and create biomass. Glucose can be catabolized to lactate in the cytoplasm, which is termed glycolysis or alternatively can be catabolized to carbon dioxide and water in the mitochondria via oxidative phosphorylation (OXPHOS). Metabolic heterogeneity exists in a subset of human tumors, with some cells maintaining a glycolytic phenotype while others predominantly utilize OXPHOS. Cells within tumors interact metabolically with transfer of catabolites from supporting stromal cells to adjacent cancer cells. The Reverse Warburg Effect describes when glycolysis in the cancer-associated stroma metabolically supports adjacent cancer cells. This catabolite transfer, which induces stromal-cancer metabolic coupling, allows cancer cells to generate ATP, increase proliferation and reduce cell death. Catabolites implicated in metabolic coupling include the monocarboxylates lactate, pyruvate and ketone bodies. Monocarboxylate transporters (MCT) are critically necessary for release and uptake of these catabolites. MCT4 is involved in the release of monocarboxylates from cells, is regulated by catabolic transcription factors such as hypoxia inducible factor 1 alpha (HIF1A) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and is highly expressed in cancer-associated fibroblasts. Conversely, MCT1 is predominantly involved in the uptake of these catabolites and is highly expressed in a subgroup of cancer cells. MYC and TIGAR, which are genes involved in cellular proliferation and anabolism are inducers of MCT1. Profiling human tumors on the basis of an altered redox balance and intra-tumoral metabolic interactions may have important biomarker and therapeutic implications. Alterations in the redox state and mitochondrial function of cells can induce metabolic coupling. Hence, there is interest in redox and metabolic modulators as anticancer agents. Also, markers of metabolic coupling have been associated with poor outcomes in numerous human malignancies and may be useful prognostic and predictive biomarkers.

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“…Therefore, any compound known as strong antioxidant is believed to protect the cardiac tissues from MI. In fact, some experimental and clinical studies have shown that myocardial infarct size can be limited by increasing endogenous antioxidants and suppression of free radical generation 7 .…”

Section: Introductionmentioning

confidence: 99%

Preventive effect of Agnucastoside C against Isoproterenol-induced myocardial injury

Panda

Kar

Biswas

2017

Sci Rep

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An iridoid glycoside, agnucastoside C (ACC) was isolated from the leaves of Moringa oliefera and its cardio protective potential was investigated in adult rats by examining the effects of this test compound, ACC at 30 mg/kg for 14 days in isoproterenol (100 mg/kg)-induced myocardial injury. Isoproterenol (ISO) administration induced the myocardial injury as evidenced by the altered ECG pattern with ST-segment elevation and an increase in the levels of cardiac injury markers including troponin-I, creatine kinase-MB, alanine transaminase, aspartate transaminase, lactate dehydrogenase; inflammatory markers, interleukine-6 and tumor necrosis factor. In this group, there was also an increase in cardiac lipid peroxidation and a decrease in cellular antioxidants. However, pretreatment with ACC maintained the normal ECG pattern and nearly normal levels of all the cardiac markers in ISO-induced animals. Electron microscopic and histological studies also showed marked reduction in ISO-induced cardiac damages including infarct size by ACC. Analysis by 2-DE revealed the involvement of 19 different cardiac proteins, associated with energy metabolism, oxidative stress and maintenance of cytoskeleton. The expression of those proteins were altered by ISO, but maintained in ACC pretreated rats. Our findings reveal the potential of isolated ACC in the prevention of myocardial damage.

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Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction])

Abstract: Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000.

Cited by 119 publications

References 53 publications

Rationale for the use of N ‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19

Rationale for the use of N ‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19

Metabolic coupling and the Reverse Warburg Effect in cancer: Implications for novel biomarker and anticancer agent development

Preventive effect of Agnucastoside C against Isoproterenol-induced myocardial injury

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