Dr. Ron’s Research Review – July 11, 2018

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This week’s research review focuses on thiocyanate.

1st Line’s patented formula makes up into a drink containing hypothiocyanite and hypothiocyannous ions, identical to those in tears, saliva and milk.

Thiocyanate (SCN) is ubiquitously found at a wide range of concentrations in the extracellular fluids of mammals, including plasma, saliva, airway epithelial lining fluid (ELF), nasal lining fluid (NLF), milk, tears, and gastric juices. (Chandler and Day, 2012)
Hypothiocyanous acid (HOSCN) is produced in biological systems by the peroxidase-catalyzed reaction of thiocyanate (SCN) with H2O2. (Barrett and Hawkins, 2012)
HOSCN inhibits bacterial glycolysis by targeting glycolytic enzymes that contain thiol groups essential for function, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hexokinase, glucose-6-phosphate dehydrogenase, and aldolase. Exposure to HOSCN also compromises the ability of bacteria to transport glucose and other essential nutrients, which may be associated with structural damage to the bacterial cell membrane or GLUT transporters. (Barrett and Hawkins, 2012)

Toxicity

The lack of toxicity in humans and the absence of damage on surfaces of fomites suggest a potential use of OSCN- to avoid mucosal and environmental transmission of influenza virus. (Cegolon et al., 2014)
Thiocyanates were used in treatment of hypertension, but discontinued due to its toxicity. (Warren et al., 1949)

 

Dr. Ron


 

Articles

Hypothiocyanous acid: benign or deadly
            (Barrett and Hawkins, 2012) Download
Hypothiocyanous acid (HOSCN) is produced in biological systems by the peroxidase-catalyzed reaction of thiocyanate (SCN(-)) with H(2)O(2). This oxidant plays an important role in the human immune system, owing to its potent bacteriostatic properties. Significant amounts of HOSCN are also formed by immune cells under inflammatory conditions, yet the reactivity of this oxidant with host tissue is poorly characterized. Traditionally, HOSCN has been viewed as a mild oxidant, which is innocuous to mammalian cells. Indeed, recent studies show that the presence of SCN(-) in airways has a protective function, by preventing the formation of other, more damaging, inflammatory oxidants. However, there is an increasing body of evidence that challenges this dogma, showing that the selectivity of HOSCN for specific thiol-containing cellular targets results in the initiation of significant cellular damage. This propensity to induce cellular dysfunction is gaining considerable interest, particularly in the cardiovascular field, as smokers have elevated plasma SCN(-), the precursor for HOSCN. This review will outline the beneficial and detrimental aspects of HOSCN formation in biological systems.

In vitro antiviral activity of hypothiocyanite against A/H1N1/2009 pandemic influenza virus.
            (Cegolon et al., 2014) Download
Influenza virus spreads via small particle aerosols, droplets and fomites, and since it can survive for a short time on surfaces, can be introduced into the nasal mucosa before it loses infectivity. The hypothiocyanite ion (OSCN-), product of the lactoperoxidase/H2O2/SCN- system of central airways, is emerging as an important molecule for innate defense mechanism against bacteria, fungi and viruses. Here we demonstrated that OSCN(-) displays virucidal activity in vitro against the A/H1N1 2009 pandemic influenza virus. The concentration required to inhibit viral replication by 50% was 2 μM when virus were challenged directly with OSCN- before cell inoculation. These values were even lower when inoculated cells were maintained in contact with enzyme free-OSCN- in the culture medium. The last experimental conditions better reflect those of tracheobronchial mucosa, where HOSCN/OSCN- is retained in the air-liquid interface and inactivates both the viruses approaching the epithelium from outside and those released from the inoculated cells after the replication cycle. Importantly no OSCN- cytotoxicity was observed in the cellular system employed. The lack of toxicity in humans and the absence of damage on surfaces of fomites suggest a potential use of OSCN- to avoid mucosal and environmental transmission of influenza virus. Since hypothiocyanite is normally present in human airways a low risk of viral resistance is envisaged. In vivo confirmatory studies are needed to evaluate the appropriate dose, regimen and formulation.

Thiocyanate: a potentially useful therapeutic agent with host defense and antioxidant properties.
            (Chandler and Day, 2012) Download
Thiocyanate (SCN) functions in host defense as part of the secreted lactoperoxidase (LPO) microbicidal pathway. SCN is the preferred substrate for LPO-driven catalytic reduction of hydrogen peroxide (H(2)O(2)) forming hypothiocyanous acid (HOSCN). HOSCN is selectively generated by many peroxidase enzymes that can utilize SCN including: eosinophil peroxidase (EPO), gastric peroxidase (GPO), myeloperoxidase (MPO), salivary peroxidase (SPO), and thyroid peroxidase (TPO). These enzymes generate HOSCN through a two-electron halogenation reaction. HOSCN is a potent microbicidal agent that kills or nullifies invading pathogens but is better tolerated by host tissue. Some controversy exists as to whether physiologic levels of HOSCN are non-toxic to host tissue, but the disagreement appears to be based on results of enzymatic generation (yielding moderate steady-state exposure) versus direct high level acute exposure in mammalian cell lines. This apparent duality is also true of other endogenous oxidants such as hydrogen peroxide and relates to the difference between physiologically relevant oxidant production versus supra-physiologic bolus dosing approaches. SCN has antioxidant properties that include the ability to protect cells against oxidizing agents such as hypochlorous acid (HOCl) and repair protein chloramines. SCN is an important endogenous molecule that has the potential to interact in complex and elegant ways with its host environment and foreign organisms. SCN's diverse properties as both host defense and antioxidant agent make it a potentially useful therapeutic.

Toxicity of Thiocyanates Used in Treatment of Hypertension
            (Warren et al., 1949) Download
The purpose of this article is to describe the toxic effects of thiocyanate as used in the treatment of hypertension, and to report a fatal case of thiocyanate poisoning. In hypertension, thiocyanate reduces the systolic and diastolic blood pressures by 60 and 40 mm. respectively, is effective against headache, and may produce a feeling of general well-being. The drug is given by mouth in 0.2 gram doses sufficient to maintain a blood level of from 5 to 14 mg. per cent. Weekly blood assays are made, and the patient closely observed for signs of toxicity, particularly a maculopapular eruption and toxic psychosis.

 


References

Barrett, TJ and CL Hawkins (2012), ‘Hypothiocyanous acid: benign or deadly’, Chem Res Toxicol, 25 (2), 263-73. PubMed: 22053976
Cegolon, L, et al. (2014), ‘In vitro antiviral activity of hypothiocyanite against A/H1N1/2009 pandemic influenza virus.’, Int J Hyg Environ Health, 217 (1), 17-22. PubMed: 23540488
Chandler, JD and BJ Day (2012), ‘Thiocyanate: a potentially useful therapeutic agent with host defense and antioxidant properties.’, Biochem Pharmacol, 84 (11), 1381-87. PubMed: 22968041
Warren, F, E Messinger, and H Morris (1949), ‘Toxicity of Thiocyanates Used in Treatment of Hypertension’, Ann Intern Med, 30 (5), 1054-59. PubMed: