Comparative study of potassium thiocyanate and other drugs in the treatment of essential hypertension

Ruskin, Arthur; McKinley, W.Frank

doi:10.1016/0002-8703(47)90347-5

Cited by 7 publications

(3 citation statements)

References 26 publications

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“…SCN treated patients were commonly observed with plasma SCN values of 400–2000 μM, with additional case reports of far higher concentrations in the literature, up to 7 mM [62,63]. Oral administration of SCN produces nearly 100% absorption in healthy subjects [28].…”

Section: Clinical History and Outcomes Of Thiocyanate Administrationmentioning

confidence: 99%

“…In the same study, patients receiving up to 600 mg per day had a median plasma level of 1500–2250 μM SCN [65]. However in another study the authors did not find significant difference in blood pressure reduction from placebo except at plasma levels that were regarded as unsafe [63]. Cardiac pathology also correlated inversely with therapeutic efficacy of SCN so that hypertensive subjects with the least chronic disease symptoms were the most likely to experience benefits [65].…”

Section: Clinical History and Outcomes Of Thiocyanate Administrationmentioning

confidence: 99%

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THIOCYANATE: A potentially useful therapeutic agent with host defense and antioxidant properties

Chandler

Day

2012

Biochemical Pharmacology

143

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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 (H2O2) 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.

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Section: Clinical History and Outcomes Of Thiocyanate Administrationmentioning

confidence: 99%

Section: Clinical History and Outcomes Of Thiocyanate Administrationmentioning

confidence: 99%

THIOCYANATE: A potentially useful therapeutic agent with host defense and antioxidant properties

Chandler

Day

2012

Biochemical Pharmacology

143

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“…Most striking are the consistently high values of SCN − in patient plasma, which were regularly maintained in a purported therapeutic range of 1.2-2.1 mM. In the few placebo-controlled trials from the contemporary literature, orally administered SCN − was only modestly more effective than placebo at lowering blood pressure [163,164]. Few if any clinical studies utilizing exogenous SCN − with therapeutic intent are known to have taken place since these; however, a non-randomized non-placebo controlled trial concerning the potential deleterious effect of exogenous SCN − on thyroid function in a susceptible population of Sudanese individuals has been published [50].…”

Section: Clinical and In Vivo Research On The Health Effects Of Scn−mentioning

confidence: 99%

Biochemical mechanisms and therapeutic potential of pseudohalide thiocyanate in human health

Chandler

Day

2015

Free Radical Research

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Thiocyanate (SCN−) is an ubiquitous molecule in mammalian biology, reaching up to mM concentrations in extracellular fluids. Two-electron oxidation of SCN− by H2O2 produces hypothiocyanous acid (HOSCN), a potent antimicrobial species. This reaction is catalyzed by chordate peroxidases (e.g., myeloperoxidase and lactoperoxidase), occurring in human secretory mucosa, including the oral cavity, airway and alimentary tract, and regulates resident and transient flora as part of innate immunity. Increasing SCN− levels limits the concentrations of a family of 2-electron oxidants (H2O2, hypohalous acids and haloamines) in favor of HOSCN formation, altering the oxidative impact on host tissue by substitution of repairable thiol and selenol oxidations instead of biomolecule degradation. This fine-tuning of inflammatory oxidation paradoxically associates with maintained host defense and decreased host injury during infections, due in part to phylogenetic differences in the thioredoxin reductase system between mammals and their pathogens. These differences could be exploited by pharmacologic use of SCN−. Recent preclinical studies have identified antimicrobial and anti-inflammatory effects of SCN− in pulmonary and cardiovascular animal models, with implications for treatment of infectious lung disease and atherogenesis. Further research is merited to expand on these findings and identify other diseases where SCN− may be of use. High oral bioavailability and an increased knowledge of the biochemical effects of SCN− on a subset of pro-inflammatory reactions suggest clinical utility.

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Beeinflussung spezieller Organe und Organsysteme durch Anionen

Eichler¹

1950

Die Pharmakologie Anorganischer Anionen

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Comparative study of potassium thiocyanate and other drugs in the treatment of essential hypertension

Cited by 7 publications

References 26 publications

THIOCYANATE: A potentially useful therapeutic agent with host defense and antioxidant properties

THIOCYANATE: A potentially useful therapeutic agent with host defense and antioxidant properties

Biochemical mechanisms and therapeutic potential of pseudohalide thiocyanate in human health

Beeinflussung spezieller Organe und Organsysteme durch Anionen

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