Mexican Study Shows That Melatonin Can Restore Redox Homeostasis Alteration In COVID-19 Patients

COVID-19 News: The COVID-19 pandemic caused by the SARS-CoV-2 virus has continued to impact global health, with millions of cases and deaths reported despite vaccination efforts. Understanding the molecular mechanisms underlying the disease's severity is crucial for developing effective treatments. Recent research from the Instituto Nacional de Cardiología Ignacio Chávez-Mexico and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán-Mexico that is covered in this COVID-19 News report, sheds light on melatonin's potential to restore redox homeostasis in COVID-19 patients.


Melatonin Can Restore Redox Homeostasis Alteration In COVID-19 Patients

Thailand Medical News had covered previous studies showing the efficacy of melatonin in preventing COVID-19 disease severity and also in assisting treating certain Long COVID conditions.
 
https://www.thailandmedical.news/news/latest-new-study-reveals-that-melatonin-supplements-can-aid-in-treating-certain-long-covid-symptoms
 
https://www.thailandmedical.news/news/study-shows-that-melatonin-based-drugs-inhibit-sars-cov-2-entry-into-the-brain-and-prevent-damage-of-cerebral-vessels-might-be-good-for-long-covid
 
https://www.thailandmedical.news/news/covid-19-supplements-yet-another-study-indicates-that-melatonin-can-prevent-severe-covid-19
 
https://www.thailandmedical.news/news/covid-19-supplements-cleveland-clinic-study-highlights-efficacy-of-melatonin-to-help-treat-covid-19
 
https://www.thailandmedical.news/news/melatonin-covid-19-columbia-university-study-shows-that-melatonin-increases-survival-rates-of-covid-19-patients-on-ventilators
 
https://www.thailandmedical.news/news/melatonin-and-covid-19:-more-studies-emerging-that-melatonin-is-useful-as-an-adjuvant-treatment-for-covid-19-due-to-its-an ti-inflammatory-properties-
 
https://www.thailandmedical.news/news/breaking-covid-19-supplements-melatonin-helps-lessen-severity-risk-in-covid-19-patients-by-preventing-cytokine-storms
 
Targeting Type II Pneumocytes: The Gateway for SARS-CoV-2
The SARS-CoV-2 virus primarily targets type II pneumocytes, initiating a cascade of events leading to oxidative stress and inflammation. This process involves the interaction of viral proteins with cellular receptors, triggering immune responses that contribute to tissue damage and disease progression.
 
The Role of Melatonin in Redox Homeostasis
Melatonin, a hormone synthesized by the pineal gland, is known for its antioxidant properties and regulatory effects on mitochondrial function. Its ability to scavenge free radicals, modulate immune responses, and promote antioxidant enzyme activity makes it a promising candidate for mitigating COVID-19-induced oxidative stress.
 
Study Design and Methodology
The study evaluated serum samples from COVID-19 patients, assessing markers of oxidative stress, antioxidant enzyme activities, and redox homeostasis before and after melatonin treatment. Key parameters included carbonyls, glutathione levels, total antioxidant capacity, nitrites, lipid peroxidation, and enzyme activities such as glutathione peroxidase and superoxide dismutase.
 
Results and Discussion
The study yielded crucial insights into the impact of melatonin on redox homeostasis in COVID-19 patients. The results, coupled with a comprehensive discussion, provide a deeper understanding of melatonin's therapeutic potential in mitigating oxidative stress and restoring cellular balance.

-Oxidative Stress Markers
The analysis of serum samples from COVID-19 patients revealed notable alterations in oxidative stress markers. Specifically, concentrations of total carbonyls and the lipid peroxidation (LPO) index were elevated in COVID-19 patients compared to healthy subjects. This elevation signifies increased oxidative damage to cellular components, including lipids, proteins, and DNA.
 
However, following treatment with melatonin, there was a significant decrease in the concentration of carbonyls and the LPO index. These findings underscore melatonin's ability to counteract oxidative stress by reducing the burden of reactive oxygen species (ROS) and mitigating cellular damage.
 
-Antioxidant Enzyme Activities
The study also investigated the activities of key antioxidant enzymes that utilize glutathione (GSH), such as glutathione peroxidase (GPx), thioredoxin reductase (TrxR), glutathione-S-transferase (GST), and glutathione reductase (GR). In COVID-19 patients, there was a notable decrease in the activities of these enzymes compared to healthy individuals. This decline reflects an impaired antioxidant defense system in response to viral infection-induced oxidative stress.
 
However, following melatonin treatment, a significant increase in the activities of these antioxidant enzymes was observed. Melatonin's ability to enhance the enzymatic antioxidant defense system highlights its role in promoting cellular resilience and combating oxidative damage. By augmenting the activities of GPx, TrxR, GST, and GR, melatonin contributes to restoring redox balance and protecting cells from oxidative injury.
 
-Redox Homeostasis Restoration
One of the most significant findings of the study was melatonin's capacity to restore redox homeostasis in COVID-19 patients. The treatment with melatonin led to increases in total antioxidant capacity (TAC), nitrite levels (NO2−), thiol groups, and glutathione (GSH) concentration. These improvements signify a shift towards a more favorable redox state, characterized by enhanced antioxidant defenses and reduced oxidative stress markers.
 
The restoration of redox homeostasis is crucial in mitigating the pathological consequences of COVID-19, such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). By modulating ROS levels and bolstering antioxidant mechanisms, melatonin emerges as a promising therapeutic adjunct in managing COVID-19-related complications.
 
Mechanisms of Melatonin Action
Melatonin's multifaceted mechanisms of action contribute to its efficacy in restoring redox balance and combating oxidative stress in COVID-19 patients. These mechanisms include:
 
-ROS Scavenging: Melatonin's chemical structure enables it to scavenge a variety of free radicals, including superoxide anions (O2−) and hydroxyl radicals (OH−). By neutralizing ROS, melatonin protects cellular structures and prevents oxidative damage.
 
-Enhancement of Antioxidant Enzymes: Melatonin stimulates the activity of key antioxidant enzymes such as GPx, TrxR, GST, and GR. These enzymes play pivotal roles in detoxifying ROS and maintaining cellular redox equilibrium.
 
-Regulation of Inflammatory Responses: Melatonin exerts anti-inflammatory effects by modulating cytokine production, particularly interleukin-6 (IL-6) levels. By dampening excessive inflammation, melatonin reduces oxidative stress associated with the cytokine storm in severe COVID-19 cases.
 
-Glucose Homeostasis Modulation: Melatonin's influence on glucose metabolism contributes to its overall antioxidant and anti-inflammatory effects. By inhibiting the Warburg effect and promoting aerobic mitochondrial function, melatonin helps restore cellular energy balance and mitigate metabolic disturbances in COVID-19 patients.
 
Implications for COVID-19 Management
The study's outcomes suggest that melatonin can serve as an adjuvant therapy for COVID-19, particularly in mitigating oxidative stress-related complications. Its role in restoring redox balance, modulating glucose metabolism, and improving inflammatory profiles highlights its therapeutic potential.
 
Clinical Significance and Future Directions
Clinical trials supporting melatonin's efficacy in COVID-19 management underscore the need for further research into optimal dosages, treatment durations, and patient populations. Integrating melatonin into comprehensive treatment protocols could enhance outcomes and reduce disease severity.
 
Conclusion
Melatonin emerges as a promising therapeutic agent for restoring redox homeostasis and mitigating oxidative stress in COVID-19 patients. Its diverse mechanisms of action and proven antioxidant effects position it as a valuable addition to the arsenal of treatments for combating SARS-CoV-2 infection and its associated complications. Future studies should delve deeper into melatonin's molecular pathways and clinical applications to optimize its therapeutic benefits in COVID-19 management.
 
The study findings were published in the peer reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/25/8/4543
 
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