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10.1111/jpi.12676

http://scihub22266oqcxt.onion/10.1111/jpi.12676
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32597503!ä!32597503

suck abstract from ncbi


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pmid32597503      J+Pineal+Res 2020 ; 69 (3): e12676
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  • Melatonin restores neutrophil functions and prevents apoptosis amid dysfunctional glutathione redox system #MMPMID32597503
  • NaveenKumar SK; Hemshekhar M; Jagadish S; Manikanta K; Vishalakshi GJ; Kemparaju K; Girish KS
  • J Pineal Res 2020[Oct]; 69 (3): e12676 PMID32597503show ga
  • Melatonin is a chronobiotic hormone, which can regulate human diseases like cancer, atherosclerosis, respiratory disorders, and microbial infections by regulating redox system. Melatonin exhibits innate immunomodulation by communicating with immune system and influencing neutrophils to fight infections and inflammation. However, sustaining redox homeostasis and reactive oxygen species (ROS) generation in neutrophils are critical during chemotaxis, oxidative burst, phagocytosis, and neutrophil extracellular trap (NET) formation. Therefore, endogenous antioxidant glutathione (GSH) redox cycle is highly vital in regulating neutrophil functions. Reduced intracellular GSH levels and glutathione reductase (GR) activity in the neutrophils during clinical conditions like autoimmune disorders, neurological disorders, diabetes, and microbial infections lead to dysfunctional neutrophils. Therefore, we hypothesized that redox modulators like melatonin can protect neutrophil health and functions under GSH and GR activity-deficient conditions. We demonstrate the dual role of melatonin, wherein it protects neutrophils from oxidative stress-induced apoptosis by reducing ROS generation; in contrast, it restores neutrophil functions like phagocytosis, degranulation, and NETosis in GSH and GR activity-deficient neutrophils by regulating ROS levels both in vitro and in vivo. Melatonin mitigates LPS-induced neutrophil dysfunctions by rejuvenating GSH redox system, specifically GR activity by acting as a parallel redox system. Our results indicate that melatonin could be a potential auxiliary therapy to treat immune dysfunction and microbial infections, including virus, under chronic disease conditions by restoring neutrophil functions. Further, melatonin could be a promising immune system booster to fight unprecedented pandemics like the current COVID-19. However, further studies are indispensable to address the clinical usage of melatonin.
  • |Animals[MESH]
  • |Antioxidants/pharmacology/*therapeutic use[MESH]
  • |Apoptosis/drug effects[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |Coronavirus Infections/drug therapy[MESH]
  • |Drug Evaluation, Preclinical[MESH]
  • |Female[MESH]
  • |Glutathione Reductase/metabolism[MESH]
  • |Glutathione/*metabolism[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Melatonin/pharmacology/*therapeutic use[MESH]
  • |Mice[MESH]
  • |Mitochondria/metabolism[MESH]
  • |NADPH Oxidases/metabolism[MESH]
  • |Neutrophils/*drug effects[MESH]
  • |Oxidative Stress/drug effects[MESH]


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