Medical News: Polish Study Finds N-Acetylcysteine And Sulodexide Exhibits Protective Properties On Endothelial Cells Exposed To SARS-CoV-2!

Medical News: The ongoing global battle against the COVID-19 pandemic has brought to light the multifaceted impact of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on the human body. Apart from the acute respiratory distress that is characteristic of the virus, there is emerging evidence of widespread complications affecting various organs, with a particular focus on the endothelial cells.


 
Researchers from Poznan University of Medical Sciences in Poland, in collaboration with Collegium Medicum, Zielona Góra, have conducted a comprehensive study investigating the protective properties of N-Acetylcysteine (NAC) and Sulodexide on endothelial cells exposed to SARS-CoV-2. This study not only sheds light on the intricacies of the virus's impact on endothelial function but also provides valuable insights into potential therapeutic avenues for the long-term effects observed in post-COVID-19 syndrome.
 
Thailand Medical News had in previous coverages extolled the benefits of N-Acetylcysteine (NAC) in the management of acute COVID-19 infections in terms of NAC as an antiviral and also in term of NAC assisting to upregulated depleted glutathione levels as a result of redox reactions.
 
https://www.thailandmedical.news/news/breaking-news-n-acetyl-cysteine-can-cause-conformational-perturbation-of-sars-cov-2-spike-protein,-indirectly-inhibiting-the-virus
 
https://www.thailandmedical.news/news/breaking-covid-19-drugs-study-shows-that-n-acetylcysteine-or-nac-is-an-effective-antiviral-and-immunomodulatory-drug-against-all-sars-cov-2-variants
 
https://www.thailandmedical.news/news/breaking-covid-19-research-russian-study-indicates-that-glutathione-deficiency-affects-covid-19-susceptibility,-nac-supplements-helps
 
https://www.thailandmedical.news/news/breaking-study-shows-that-sars-cov-2-infections-lead-to-increased-levels-of-oxidative-stress,-oxidant-damage-and-glutathione-deficiency
 
Understanding SARS-CoV-2 and Endothelial Dysfunction
SARS-CoV-2, the virus responsible for COVID-19, infiltrates cells in the respiratory system, primarily targeting endothelial cells. This invasion triggers a cascade of events leading to hyperinflammation, activation of the coagulation cascade, and, consequently, endothelial dysfunction. Endothelial dysfunction is characterized by th e depletion of nitric oxide (NO), cellular oxidative stress, an inflammatory response, and damage to the glycocalyx structure - a protective layer covering the endothelial cells.
 
Notably, myocarditis, a complication of COVID-19, exacerbates endothelial cell dysfunction. The impact on coronary artery endothelial cells may contribute to the long-term effects observed in post-COVID-19 syndrome, affecting between 10% and 30% of patients.
 
N-Acetylcysteine (NAC) and Sulodexide: Potential Mitigators of Endothelial Damage
NAC and Sulodexide have emerged as promising candidates for mitigating endothelial damage and dysfunction in the context of SARS-CoV-2 infection. NAC, renowned for its anti-inflammatory properties, suppresses the secretion of pro-inflammatory cytokines, including NF-κB, IL-8, and IL-6. Furthermore, NAC has demonstrated a protective role in reducing the replication of various viruses, such as the human immunodeficiency virus (HIV) and the respiratory syncytial virus (RSV). These protective effects reduce the adverse impact of viruses on vascular endothelium.
 
Additionally, prior research on other RNA viruses has suggested that NAC might also play a similar role in SARS-CoV-2 infection, including the potential ability to inhibit its replication. Sulodexide, a glycosaminoglycan mixture comprising 20% dermatan sulfate and 80% fast-moving heparin, has shown supportive effects in the acute phase of COVID-19 in the literature.
 
The Study: Probing into Protective Effects on Coronary Artery Endothelial Cells
The researchers focused their attention on coronary artery endothelial cells (CAEC) and sought to understand the influence of serum collected from post-COVID-19 patients on these cells. In particular, they measured concentrations of interleukin 6, von Willebrand Factor, tissue Plasminogen Activator, and Plasminogen Activator Inhibitor-1. To assess potential protective roles, the cultures were incubated with NAC and Sulodexide.
 
Results: Illuminating Protective Mechanisms
The study revealed significant differences in blood inflammatory parameters between the post-COVID-19 group and the control group. Notably, the post-COVID-19 serum induced oxidative stress and increased pro-inflammatory cytokine synthesis in CAEC. However, the supplementation of post-COVID-19 serum with NAC or Sulodexide demonstrated a mitigating effect.
 
Specifically, NAC supplementation reduced the intracellular oxidative stress by 23%. Post-COVID-19 serum stimulated the synthesis of IL-6 in CAEC, but NAC or Sulodexide supplementation reduced this synthesis by 18% and 24%, respectively. Von Willebrand Factor (vWF) synthesis, increased in CAEC exposed to post-COVID-19 serum, was reduced by 30% with NAC supplementation.
 
Interestingly, the study observed no changes in the synthesis of tissue Plasminogen Activator (tPA). However, the synthesis of Plasminogen Activator Inhibitor-1 (PAI-1) increased in endothelial cells exposed to post-COVID-19 serum. NAC was effective in reducing the stimulatory effect of post-COVID-19 serum on the synthesis of PAI-1 in CAEC by 17%. Both NAC and Sulodexide increased the tPA/PAI-1 ratio, reflecting enhanced fibrinolytic activity.
 
Discussion: Implications for Post-COVID-19 Syndrome
The post-COVID-19 syndrome, with its long-term and varied effects, remains a complex and poorly understood aspect of the disease. The study contributes significantly by demonstrating that endothelial inflammation induced by SARS-CoV-2 may persist months after infection. Serum markers of endothelial injury may remain elevated even eight months post-infection.
 
The study underscores the importance of sulfation of heparan sulfate in the glycocalyx as a factor influencing susceptibility to SARS-CoV-2 infection. Oxidative stress and proteolysis during infection lead to the rapid depletion of sulfur amino acids. Sulfur donors, such as NAC and Sulodexide, play a beneficial role in protecting endothelial cells from injury. NAC, in particular, has been shown to replenish sulfur amino acids rapidly following supplementation during the acute phase of infection.
 
Implications for Thromboembolic Complications
Thromboembolic complications associated with COVID-19 are monitored through biomarkers like D-dimers, fibrinogen, and von Willebrand Factor. Endothelial dysfunction biomarkers such as vWF and PAI-1 are elevated in COVID-19 patients, often associated with severe forms of the disease and high mortality. Notably, this study highlights that sustained endotheliopathy, as measured by vWF levels, can persist up to four months after infection.
 
Conclusion: NAC and Sulodexide as Guardians Against Endothelial Injury
In conclusion, this in-depth study from Poland significantly advances our understanding of potential therapeutic interventions for post-COVID-19 syndrome. The persistent risk of endothelial cell injury months after infection emphasizes the need for targeted approaches. NAC emerges as a potential guardian, reducing myocardial injury by mitigating endothelial damage in coronary arteries. Simultaneously, Sulodexide shows promise in protecting endothelial cells, particularly in patients with or after COVID-19 infection. As research continues to unfold, these findings provide a foundation for further exploration and development of targeted therapeutic strategies to address the lingering effects of COVID-19 on endothelial health.
 
The study findings were published in the peer reviewed journal: Frontiers in Cellular and Infection Microbiology.
https://www.frontiersin.org/articles/10.3389/fcimb.2023.1268016/full
 
Please note: Do not attempt to take N-Acetylcysteine Supplements without consulting a doctor or any medical professional as wrong dosing or usage of these supplements can even result in development and progression of various lung cancers besides lung and liver damage.
 
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