Scientists Explain How Selenium Fights Ebola Virus Disease (EVD)
1. Inhibitory Effect of Selenite and Other Antioxidants on Complement-Mediated Tissue Injury in Patients with Epidemic Hemorrhagic Fever. Jian-Cun Hou, Biological Trace Element Research 1997;56:125-130
"Years of research on anti-inflammatory studies have made the author believe complement plays a central role in EHF [epidemic hemorrhagic fever] pathogenesis.”
“The activation of the complement system by immune complexes also brings the concerted toxic products from activated polymorphs’ respiratory burst, resulting in further activation of complement, thus forming an amplification feedback cycle, which gives greater inflammation and tissue injury.”
“Selenium….was found to possess an inhibitory effect on complement activation”
“the author has proposed….a new therapeutic approach [to treating] hemorrhagic fever.”
“the ‘anti-inflammatory’ approach to treat [hemorrhagic fever] disease in relation to immune complexes formation has been successfully carried out in the treatment of EHF [epidemic hemorrhagic fever] during an epidemic episode in the Henan province by administration of sodium selenite alone. ”
“These EHF cases were treated by multiple oral doses of 2 mg selenite [per day] in the first 9 days of hospitalization in addition to the general management of 80 cases, including fulminant, severe, and moderate types.”
“Admirable results were obtained: a) The key role of complement activation in pathogenesis of EHF was identified; b) A remarkable therapeutic effect was observed, since the mortality of EHF fulminant cases was reduced from 100% of the untreated cases to 36.6% by treatment with selenite; and c) The inhibition of complement and platelets by selenite was indeed effective.”
2. Computational Genomic Analysis of Hemorrhagic Fever Viruses. Chandra Sekar Ramanthan and Ethan Will Taylor, Biological Trace Element Research 1997;56:93-105
“A number of distinct viruses are known as hemorrhagic fever viruses based on a shared ability to induce hemorrhage by poorly understood mechanisms, typically involving the formation of blood clots (disseminated intravascular coagulation). It is well documented that selenium plays a significant role in the regulation of blood clotting via its effects on the thromboxane/prostacyclin ratio, and effects on the complement system. Selenium has an anticlotting effect, whereas selenium deficiency has a pro-clotting or thrombotic effect. It is also well documents that extreme dietary selenium deficiency, which is almost never seen in humans, has been associated with hemorrhagic effects in animals. Thus, the possibility that viral selenoprotein synthesis might contribute to hemorrhagic symptoms merits further consideration.”
“One potential [Ebola] viral selenoprotein may contain up to 16 selenium atoms per molecule. Biosynthesis of this protein could impose an unprecedented selenium demand on the host, potentially leading to severe lipid peroxidation and cell membrane destruction, and contributing to hemorrhagic symptoms.” “Hemorrhage can occur by several mechanisms which may be interrelated. One is the dysfunction and damage of endothelial cells, which form the inner surface of blood vessels. Another mechanism is hemorrhagic conditions induced by complement activation. Extensive complement activation precedes onset of shock…” “Another fundamental mechanism in the production of DIC [disseminated intravascular coagulation] is via the formation of blood clots. The severe hemorrhaging produced by Ebola virus is essentially owing to the formation of blood clots – the “coagulation” of DIC – which leads to the obstruction and rupture of small blood capillaries. Thus, the hemorrhagic symptoms may be in large part a consequence of clot formation.
“Significantly, it is well documented that selenium plays a major role in the regulation of blood clotting via its effects on the thromboxane and prostacyclin ratio. Prostacyclin and thromboxane…. are involved in controlling platelet activity and vascular tone.…. Clearly, the net effect of selenium supplementation is an increased PG12/TXA2 ratio, which will inhibit clot formation. Thus one would expect selenium to tend to reduce DIC, and the associated hemorrhagic symptoms. Conversely, any virally induced selenium depletion…could favor hemorrhagic conditions. ”
“Similar hemorrhagic conditions have been seen in goats, elk, and lamb when fed on a selenium-deficient diet. Thus, both biochemical and in vivo studies show that selenium deficiency or selenium depletion can lead to hemorrhagic manifestations, probably via pro-clotting mechanisms.”
“These observations suggest that selenium might also be involved in the hemorrhagic manifestations seen in hemorrhagic viral diseases. If so, selenium could act by various mechanisms, either by exerting its effects in endothelial cells, on complement activation, or by affecting the PG12/TXA2 ratio and thus blood clotting. A significant role for selenium appears to be strongly supported by the results of Hou and coworkers, who treated victims of an Asian outbreak of viral hemorrhagic fever with high- dose oral sodium selenite, obtaining dramatic reductions in mortality. ”
“We have previously demonstrated the potential for selenoproteins to be encoded in [chromosome] regions overlapping known genes in HIV-1, Coxsackie virus B3, and Ebola virus. In each case, the link between selenium deficiency and the associated viral diseases (Aids, viral myocarditis, and hemorrhagic conditions, respectively) is supported by an extensive body of literature.”
“We recently reported theoretical molecular evidence that the highly pathogenic Zaire strain of the Ebola virus may be dependent on selenium owing to the presence of several PPCRs in the Ebola genome containing clusters of up to 17 in-frame UGA codons.”
“Selenium deficiency can weaken the immune system’s ability to fight viral infection, permitting increased replication, rapid mutation, and facilitating the emergence of more virulent strains. ...virally encoded selenoproteins may be a novel contributing factor to increased viral pathogenicity under conditions of selenium deficiency.”
“our analysis of Ebola suggests the presence of UGA-rich PPCPs and the potential SECIS elements may indicate depletion of host selenium by the programmed synthesis of specific selenoproteins. ”
“In conclusion, our analysis suggests that severe infection by Ebola and some other hemorrhagic fever viruses could produce an artificial and extreme selenium depletion, resulting in extensive cellular damage owing to lipid peroxidation, combined with enhanced thrombosis.”
“Our theoretical findings in regard to hemorrhagic fever viruses suggest that a viral requirement or utilization of selenium...may be a significant mechanism contributing to increased pathogenicity under conditions of selenium depletion in human and animal populations.”
3. Genomic Structures of Viral Agents in Relation to the Biosynthesis of Selenoproteins. Ethan Will Taylor et.al., Biological Trace Element Research,1997;56:63-91
“extreme selenium deficiency can induce a pro-clotting or hemorrhagic effect…”
“selenium deficiency has been linked to the incidence, disease progression, or virulence associated with a number of viral infections….Furthermore, selenium has been shown to have significant chemoprotective effects against a number of human and animal viruses, including….viral hemorrhagic fever.…Furthermore, there is now extensive evidence of a role for oxidative stress in the pathogenesis of [HIV] viral infection.”
“It is possible that the explanation for this inverse correlation between host selenium/antioxidant levels and viral pathogenesis...can be largely explained in terms of our current understanding of the importance of antioxidants for proper immune cell functioning, the role of oxidant tone in regulating gene expression, and the demonstrated ability of oxidative stress to activate viral replication.”
“Because of the known role of selenium in blood-clotting mechanisms and the thrombotic and even hemorrhagic effects of selenium deficiency, we have been particularly interested in the possibility that hemorrhagic fever viruses might be able to incorporate selenium-C in some viral proteins.”
“The causative agents in viral hemorrhagic fevers are generally single-stranded RNA viruses…”
“There is no doubt that selenium has an effect on viruses…”
4. Selenium and Viral Diseases: Facts and Hypotheses. Ethan Will Taylor, Journal of Orthomolecular Medicine, 1997;12:227-239
“Selenium is...critical [as].…an essential component of glutathione peroxidase. ….this enzyme is essential for combating the ubiquitous and harmful process of lipid peroxidation (a result of oxidative stress).”
“The highly pathogenic Zaire strain of Ebola virus….selenoprotein which would require 16 selenium atoms per molecule. This suggests that infections with Ebola Zaire may place an unprecedented demand for selenium on the host, potentially causing a more dramatic selenium depletion in a matter of days than HIV infection can accomplish in ten years. ....A potential role for selenium is highly consistent with key aspects of Ebola pathology including its effects on selenium-rich tissues like blood cells and liver, and the hemorrhaging due to rupture of capillaries obstructed by blood clots because selenium normally plays a role in inhibiting clotting, and selenium deficiency has been associated with thrombosis and even hemorrhaging in extreme cases in animals.”
“Selenium has apparently been used with considerable success by the Chinese in the palliative treatment of viral hemorrhagic fever caused by Hantan virus infection. In an outbreak involving 80 patients, oral sodium selenite at 2 mg per day for 9 days was used to achieve a dramatic reduction in the overall mortality rate, which fell from 38% (untreated control group) to 7% (selenium treatment group), thus giving an 80% reduction in mortality. This result, obtained using selenium at a dose of about 13 times the RDA as the sole therapy, is all the more striking in light of the fact that, according to conventional medical science, there is no effective treatment for hemorrhagic fever (viral infection with Ebola-like symptoms). Although this did not involve Ebola virus, there are a number of different hemorrhagic fever viruses, and they may share common mechanisms. This example suggests that pharmacological doses of selenium may also have some benefit in infections due to other hemorrhagic fever viruses, including Ebola.”
“There is now little reason to doubt that some viruses encode selenoproteins.”
“The growing body of evidence that selenium has apparent chemoprotective effects vs. a number of viral infections including HIV was attested by and documented in the recent conference on selenium and human viral diseases held in Germany in April 1996…”
“It is important to realize that when we talk about selenium we are fundamentally talking about nutrition, not a drug.”
“the danger of serious toxicity with selenium supplementation has been exaggerated. The threat of serious acute toxicity with supplementation is in my opinion nonexistent at doses less than 1000mcg per day…”
“localized or global depletion of selenium in the food chain could be a significant factor contributing to our increased susceptibility to emerging viral disease…”
5. Selenium, Systemic Immune Response Syndrome, Sepsis, and Outcome in Critically Ill Patients. Xavier Forceville et.al., Critical Care Medicine 1998;26:9:1536-1544
“Plasma selenium concentration was low in all patients with severe sepsis and septic shock…”
“…pneumonia, organ system failure, and mortality was three times higher in patients with low plasma selenium concentrations…”
“This prolonged decrease in selenium concentrations could explain the three-fold increases in morbidity and mortality rates in these patients compared with other ICU patients.”
“These selenoenzymes….play a unique role in protecting cells against the numerous cytopathologic effects of lipid peroxidation, especially membrane lipid peroxidation induced in conditions of oxidative stress.”
“The onset of low plasma selenium concentrations occurred very rapidly in the critical illness.”
“…lipid peroxides….[are] highly detrimental to membrane structure and function.”
“Selenium deficiency might increase the thromboxane A2/prostacyclin ratio thereby increasing vasoconstriction and blood coagulation.”
“…selenium deficiency affects all the components of the immune system…”
“…low plasma selenium concentrations are common in acute illness.”
6. Micronutrient Selenium Deficiency Influences Evolution of Some Viral Infectious Diseases. [Review] Michalan Harthill, Biological Trace Element Research, DOI 10.1007/s12011-011-8977-1
“When selenium-deficient virus-infected hosts were supplemented with dietary selenium, viral mutation rates diminished and immunocompetence improved.”
“Left unchecked, hyper-oxidation disrupts biomolecules, cellular lipid membranes, organ tissue, metabolic pathways and genetic mechanisms.”
“During selenium-deficient host conditions, transcription of GPx1 (glutathione peroxidase-1) falls disproportionally to 10% of selenium replete levels, and the limited nutrient is shunted elsewhere to meet other physiologic functions in selenium-requiring tissues. Discrepancy between concurrent heightened immune system requirements for GPx1 during viral infection and its diminished production help define the role of selenium in the etiology of viral infectious diseases.”
“HIV/Aids and Ebola hemorrhagic fevers originated in [selenium] nutrient-depleted regions of sub-Saharan Africa.”
“…T cells and their induced immunoglobulins and gamma-interferon are undetected in symptomatic EBOV- infected mammals, including humans, which succumb to the systemic disease. This pattern of disabled T cell function is reminiscent of selenium-deficiency effects on influenza virus-infected T cells.”
7. Selenium and Cardiovascular Disease. O. Oster and W. Prellwitz, Biological Trace Element Research, 1990;24:91-102
“In selenium deficiency an accumulation of lipid peroxidases….may occur…”
“An increased concentration of lipid peroxides owing to selenium deficiency may shift the prostaglandin synthesis from prostacyclin to thromboxane, causing enhanced blood pressure and platelet aggregability.”
“Selenium…deficient pigs develop epicardial and myocardial hemorrhage.”
8. Aspirin Inhibits Both Lipid Peroxides and Thromboxane in Preeclamptic Placentas. Yuping Wang and Scott W. Walsh, Free Radical Biology & Medicine,1995;18:3:585-591
“Preeclampsia is associated with an imbalance of increased thromboxane and decreased prostacyclin, as well as with an imbalance of increased lipid peroxides and decreased antioxidants. ….aspirin selectively inhibits thromboxane…. aspirin might also inhibit the synthesis of lipid peroxides.” “aspirin…. significantly inhibited both lipid peroxides and thromboxane”
“Thromboxane is a potent vasoconstrictor, a potent stimulator of platelet aggregation”
“ [Lipid] Peroxides are toxic compounds that damage cells and can inhibit prostacyclin synthesis. Peroxides stimulate thromboxane production….”
“aspirin should inhibit lipid peroxides, as well as thromboxane.”
“this study demonstrates that aspirin inhibits, in a dose-dependent manner, the production rates of both lipid peroxides and thromboxane….”
“our results demonstrating that inhibition of PGH2 synthesis by aspirin resulted in decreased production of lipid peroxides, as well as thromboxane.”
Comments
Post a Comment