Nitric Oxide: The Missing Factor in COVID-19 Severity?

Nikolaidis, Alexandros; Kramer, Ron; Ostojić, Sergej M.

doi:10.3390/medsci10010003

Cited by 14 publications

(17 citation statements)

References 91 publications

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“…An inducible NO synthase (NOS2, ENSG00000007171) was downregulated at the transcript level (–2.5 log-fold change; p = 3.36 × 10 −6 ). NOS2 generates NO, a messenger molecule with diverse functions in multiple human tissues [ 43 , 44 , 45 ]. Transcription of the arginine synthase ARG2 was also downregulated ( Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms behind Safranal’s Toxicity to HepG2 Cells from Dual Omics

et al. 2022

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The spice saffron (Crocus sativus) has anticancer activity in several human tissues, but the molecular mechanisms underlying its potential therapeutic effects are poorly understood. We investigated the impact of safranal, a small molecule secondary metabolite from saffron, on the HCC cell line HepG2 using untargeted metabolomics (HPLC–MS) and transcriptomics (RNAseq). Increases in glutathione disulfide and other biomarkers for oxidative damage contrasted with lower levels of the antioxidants biliverdin IX (139-fold decrease, p = 5.3 × 105), the ubiquinol precursor 3-4-dihydroxy-5-all-trans-decaprenylbenzoate (3-fold decrease, p = 1.9 × 10−5), and resolvin E1 (−3282-fold decrease, p = 45), which indicates sensitization to reactive oxygen species. We observed a significant increase in intracellular hypoxanthine (538-fold increase, p = 7.7 × 10−6) that may be primarily responsible for oxidative damage in HCC after safranal treatment. The accumulation of free fatty acids and other biomarkers, such as S-methyl-5′-thioadenosine, are consistent with safranal-induced mitochondrial de-uncoupling and explains the sharp increase in hypoxanthine we observed. Overall, the dual omics datasets describe routes to widespread protein destabilization and DNA damage from safranal-induced oxidative stress in HCC cells.

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Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms behind Safranal’s Toxicity to HepG2 Cells from Dual Omics

et al. 2022

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“…Gould et al [ 135 ] found that NO production was associated with oxidative stress caused by many types of viral infections. However, Nikolaidis et al [ 136 ] concluded that the comorbidities associated with negative clinical patient outcomes of COVID-19 sickness are linked to depletion of NO in the body.…”

Section: Identification Of Covid-19-specific Chemical Biomarkersmentioning

confidence: 99%

“…The increased severity of COVID-19 symptoms associated with old age and the age-related decline of NO levels have tied low NO levels to all major high-risk groups of COVID-19 infection. This correlation of low NO levels to increased COVID-19 infection severity and COVID-exclusive symptomatology, along with successful utilization of NO gas as a therapeutic option, should stimulate further research on this basis to further improve COVID-19 treatment options [ 136 ].…”

Section: Identification Of Covid-19-specific Chemical Biomarkersmentioning

confidence: 99%

Potential for Early Noninvasive COVID-19 Detection Using Electronic-Nose Technologies and Disease-Specific VOC Metabolic Biomarkers

Wilson

Forse

2023

Sensors

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The established efficacy of electronic volatile organic compound (VOC) detection technologies as diagnostic tools for noninvasive early detection of COVID-19 and related coronaviruses has been demonstrated from multiple studies using a variety of experimental and commercial electronic devices capable of detecting precise mixtures of VOC emissions in human breath. The activities of numerous global research teams, developing novel electronic-nose (e-nose) devices and diagnostic methods, have generated empirical laboratory and clinical trial test results based on the detection of different types of host VOC-biomarker metabolites from specific chemical classes. COVID-19-specific volatile biomarkers are derived from disease-induced changes in host metabolic pathways by SARS-CoV-2 viral pathogenesis. The unique mechanisms proposed from recent researchers to explain how COVID-19 causes damage to multiple organ systems throughout the body are associated with unique symptom combinations, cytokine storms and physiological cascades that disrupt normal biochemical processes through gene dysregulation to generate disease-specific VOC metabolites targeted for e-nose detection. This paper reviewed recent methods and applications of e-nose and related VOC-detection devices for early, noninvasive diagnosis of SARS-CoV-2 infections. In addition, metabolomic (quantitative) COVID-19 disease-specific chemical biomarkers, consisting of host-derived VOCs identified from exhaled breath of patients, were summarized as possible sources of volatile metabolic biomarkers useful for confirming and supporting e-nose diagnoses.

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“…Although multiple clinical trials for iNO are currently underway for use in COVID-19 ( Table 2 ), questions remain about dosage, frequency, and duration of administration - whether low dose continuous inhalation or short bursts of high dose NO like that in cigarettes [ 197 ]. Additionally, the requirement for skilled technicians, attributed financial costs, and possible adverse effects, including methemoglobinemia [ 282 ], etc., have been cited as potential obstacles to the clinical use of iNO. However, developing alternatives such as NONS, still requiring Phase 3 investigation, may reduce some of these challenges.…”

Section: No Delivery Platformsmentioning

confidence: 99%