PMC:7102583 / 16873-18753 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7102583","sourcedb":"PMC","sourceid":"7102583","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7102583","text":"7 Melatonin \u0026 other supportive adjuvant effects\nThe integrity of the vascular endothelial barrier is crucial in the immunoregulation within alveoli. Severe inflammation and immune responses induce epithelial and endothelial cell apoptosis, as well as increasing the production of VEGF, which aggravates edema and the extravasation of the immune cells from blood vessels. Experimental evidence suggests that melatonin mediates the suppression of VEGF in vascular endothelial cells [62]. Based on clinical reports of COVID-19, patients with severe ALI/ARDS may also have an increased risk of sepsis and cardiac arrest [2]. Published reports indicate that the application of melatonin may ameliorate the septic shock via the NLRP3 pathway [63]. Specifically, melatonin may a have preventive effect against sepsis-induced renal injury, septic cardiomyopathy and liver injury [[64], [65], [66]]. It was also reported that melatonin had benefits in patients with myocardial infarction, cardiomyopathy, hypertensive heart diseases and pulmonary hypertension, and probably functions via the TLR4/survivor activating factor enhancement pathway [67]. Moreover, melatonin exerts neurological protection by reducing the cerebral inflammatory response, cerebral edema and brain-blood barrier permeability under a number of experimental conditions [68]. In the ICU, deep sedation is associated with increased long-term mortality, and the application of melatonin reduces sedation use and the frequency of pain, agitation, anxiety [69,70]. Also, a recent meta-analysis showed that melatonin improves sleep quality in patients in the ICU [71]. Thus, the rationale for the use of melatonin in COVID-19 patients not only focuses on the attenuation of the infection-induced respiratory disorders, but also on an overall improvement and prevention of patients' wellbeing and potential 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