Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19.

The coronavirus, COVID-19, has infected hundreds of thousands and killed tens of thousands of individuals worldwide. This highly infectious condition continues to ravage the world population and has yet to reach it peak infective rate in some countries. Many conventional drugs including hydroxychloroquine/chloroquine, lopinavir, remdesivir, etc., have been repurposed as treatments for this often deadly disease, but there is no specifically-designed effective drug available; also, the drugs mentioned have significant side effects and their efficacy is unknown. New drugs and vaccines are being designed as COVID-19 treatment, but their development and testing will require months to years. Time is not a luxury that this crisis has. Thus, there is a serious unmet need for the identification of currently-available and safe molecules which can be used to slow or treat COVID-19 disease. Here, we suggest melatonin be given consideration for prophylactic use or treatment alone or in combination with other drugs. Melatonin's multiple actions as an anti-inflammatory, anti-oxidant, and anti-viral (against other viruses) make it a reasonable choice for use. Melatonin is readily available, can be easily synthesized in large quantities, is inexpensive, has a very high safety profile and can be easily self-administered. Melatonin is endogenously-produced molecule in small amounts with its production diminishing with increased age. Under the current critical conditions, large doses of melatonin alone or in combination with currently-recommended drugs, e.g., hydroxychloroquine/chloroquine, to resist COVID-19 infection would seem judicious.

Effects of selenium on liver and muscle contents and urinary excretion of zinc, copper, iron and manganese.

Selenium is a main component of glutathione peroxidase (GPX), a key antioxidant enzyme. Other elements, such as zinc, copper, manganese and iron, are also involved in the pathogenesis of oxidative damage as well as in other important metabolic pathways. The effects of selenium supplementation on the metabolism of these elements have yield controversial results .The aim of this study is to analyse the effects of selenium supplementation on liver, muscle and urinary excretion of zinc, copper, iron and manganese in a situation of oxidative stress, such as protein deficiency. The experimental design included four groups of adult male Sprague-Dawley rats, which received the Lieber-DeCarli control diet, an isocaloric 2 % protein-containing diet and another similar two groups to which selenomethionine (6 mg/l liquid diet) was added. After sacrifice (5 weeks later), muscle, liver and serum selenium were determined, as well as muscle, liver and urinary zinc, copper, manganese and iron and liver GPX activity and liver malondialdehyde. Selenium addition led to decreased liver copper, increased muscle copper, increased copper excretion and increased liver iron, whereas zinc and manganese parameters were essentially unaltered. Muscle, liver and serum selenium were all significantly correlated with liver GPX activity.

Relative and combined effects of selenium, protein deficiency and ethanol on bone.

UNLABELLED: Some observations suggest that oxidative damage may affect both osteoblastic function and osteoclastic activity in alcohol-mediated bone alterations. Selenium, a potent antioxidant, is decreased in alcoholics. OBJECTIVE: To analyse if the supplementation with selenium may alter bone changes observed in a murine model fed ethanol and/or a 2% protein-containing diet, following the Lieber-deCarli design. MATERIAL AND METHOD: Adult male Sprague-Dawley rats were divided into 8 groups, which received the Lieber-DeCarli control diet, an isocaloric, 36% ethanol-containing diet, an isocaloric, 2% protein-containing diet; and an isocaloric diet containing 2% protein and 36% ethanol diet, and another similar four groups to which selenomethionine (1mg/kg body weight). After sacrifice (5 weeks later), trabecular bone mass was histomorphometrically assessed, bone and serum selenium were determined by flame atomic absorption spectrophotometry, and serum osteocalcin, insulin growth factor 1 (IGF-1), PTH and telopeptide, by radioimmunoanalysis. Liver glutathione peroxidase (GPX) activity was also determined. RESULTS: Ethanol-fed rats showed decreased TBM, IGF-1 and osteocalcin, especially when ethanol was added to a 2%-protein diet. Selenium did not modify at all bone parameters, despite a marked increase in serum selenium and a less pronounced one in bone selenium, and an increase in liver GPX. CONCLUSION: Our results do not support the existence of a beneficial effect of selenium addition on bone changes observed in this murine model treated following the Lieber-deCarli experimental design.

Relative and combined effects of chronic alcohol consumption and HCV infection on serum zinc, copper, and selenium.

In alcoholic hepatitis, Kupffer cells are activated by intestinal gram-bacteria, leading to cytokine production and free radicals release, which, enhancing cytokine secretion, create a positive feedback loop which contributes to liver inflammation. Free radicals also damage the liver in chronic hepatitis C virus (HCV) infection, a condition frequently associated to alcohol consumption. In both situations, activity of antioxidant enzymes and of its cofactors zinc (Zn), selenium (Se), and copper (Cu) is important. This study was performed to assess the relative and combined effects of chronic alcoholism and HCV infection on serum Se, Zn, and Cu, and its relation with serum malondialdehyde (MDA) and tumor necrosis factor-α, interferon-γ, and interleukins (IL) 4, 6, and 8, in 19 HCV- alcoholic patients, 12 HCV+ alcoholic patients, nine HCV+ non-alcoholic patients, and 20 controls. Serum Zn and Se were lower in both HCV+ and HCV- alcoholic patients, whereas serum Cu was lower in HCV+ individuals. Serum Zn and Se were related to liver function derangement. MDA levels were higher in alcoholics, but no relation was observed between trace elements and MDA or cytokines, so that our results do not support a relevant role of the analyzed trace elements in the pathogenesis of chronic liver disease.