What is Zinc pyrithione It is a derivative of the antibiotic aspergillic acid with the chemical name: Bis[(2-pyridyl-1-oxo)-thio]zinc What is it for? Zinc pyrithione has antifungal, antim ...

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What is Zinc pyrithione

It is a derivative of the antibiotic aspergillic acid with the chemical name: Bis[(2-pyridyl-1-oxo)-thio]zinc

What is it for?

Zinc pyrithione has antifungal, antimicrobial,  and anti-seborrheic effects.

Zinc pyrithione or pyrithione of zinc is used both in medicine and in cosmetics and therefore its evaluation depends on the use.

Use in medicine:

Zinc pyrithione or zinc pyrithione is generally used to prevent dandruff and to contain excess sebum.

Applications

Zinc pyrithione (ZPT) is an active material that has been used for over 50 years to effectively treat dandruff and seborrheic dermatitis (D/SD). It has become the most common material for that purpose, its use has expanded to include other skin benefits such as skin hygiene. However, there is much about ZPT that is unappreciated. It is a rationally developed molecule that was modeled after the naturally occurring antimicrobial aspergillic acid. The molecular basis for its antifungal activity has been elucidated. The efficacy of ZPT originates from two attributes. First, it has a very broad antimicrobial spectrum of activity, including fungi, gram-positive and -negative bacteria. Second, the material has very low solubility, resulting in formulation and delivery as a particulate material, which has distinct performance advantages. The particles are deposited and retained on the target skin surfaces even when delivered from rinse-off products. These particles slowly release molecularly active material to interact with the surface fungal and bacteria cells to control their population, functioning as slow-release reservoirs to provide extended and persistent benefits. This particulate nature, though, results in complex pharmaceutics to realize the full efficacy benefits; it is common to see products with the same ZPT level having widely varying levels of clinical performance. Several product matrix-determined factors directly impact resultant benefits: ZPT must be retained on the skin surface achieving uniform spatial distribution laterally as well as within hair follicles (especially on scalp); ZPT must be maintained as a physically stable dispersion in product; ZPT must be maintained in a chemically active form as there are many chemical reactions that can occur that can harm ZPT bioactivity. The benefits achievable by employing ZPT require significant pharmaceutics expertise to realize the full benefits of this active material (1).

A premise on zinc

To assess the significance of zinc in the etiology of various dermatological conditions and examine the role of zinc as a mode of treatment for a wide range of dermatoses. Generally, it seems that with the exception of systemic deficiency states, there is very little evidence to convincingly demonstrate the efficacy of zinc as a first-line treatment for any dermatological conditions. Further research is needed in order to establish the indications for zinc treatment in dermatology, optimal mode of delivery, type of compound and therapeutic indexes (2).

The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. Recent studies suggested that zinc pyrithione, an FDA-approved antidandruff agent, may have antitumor activity, but the detailed molecular mechanisms remain unclear. Here we report that zinc pyrithione (ZnPT) targets the proteasome-associated DUBs (USP14 and UCHL5) and inhibits their activities, resulting in a rapid accumulation of protein-ubiquitin conjugates, but without inhibiting the proteolytic activities of 20S proteasomes. Furthermore, ZnPT exhibits cytotoxic effects against various cancer cell lines in vitro, selectively kills bone marrow cells from leukemia patients ex vivo, and efficiently inhibits the growth of lung adenocarcinoma cancer cell xenografts in nude mice. This study has identified zinc pyrithione, an FDA-approved pharmacological agent with potential antitumor properties as a proteasomal DUB inhibitor (3).

Safety

Shampoo-induced allergic contact dermatitis is difficult to diagnose clinically because it can involve multiple and variable areas where the shampoo flows. Zinc pyrithione is a common active agent in medicated shampoo that is known to have good anti-dandruff and antifungal effects. Despite its low risk of sensitization, cases of allergic contact dermatitis still occur because of the popularity of such products. We report a 33-year-old man who developed pruritic rash on his scalp, face, neck, and hands after using a new shampoo containing zinc pyrithione. A patch test revealed a positive reaction to zinc pyrithione and personal shampoo containing zinc pyrithione (4).

It was authorised as a preservative at the maximum concentration of
0.5% with the limitation "Authorized in products rinsed off after use, forbidden in products for oral hygiene" (5).

Zinc pyrithione (ZP) is commonly used to prevent dandruff and seborrheic dermatitis. Many consumers are exposed daily to high doses of ZP, causing serious concerns about its toxicity. The reproductive and developmental toxicities were previously reported in pregnant rats. However, the estrogenic activity of ZP at varying degrees of exposure has been rarely studied. Thus, we performed an uterotrophic assay, E-screen assay, and gene expression profiling to assess the estrogenic activity of ZP. For the uterotrophic assay, ZP (2, 10, or 50 mg/kg/d) was subcutaneously administered to ovariectomized rats every day for three days. Uteri were extracted 24 hours after the last dose. Then, wet and blotted uterine weights were measured. For the E-screen essay, MCF-7 cells (a breast cancer cell line) were exposed to 10-9 to 10-6 M of ZP, and cell proliferation was then measured. For the gene expression analysis, changes of gene expression levels in uterine samples taken for the uterotrophic assay were analyzed. In the uterotrophic assay, the concentration of ZP had no significant effect on uterine weight. In the E-screen assay, ZP at any concentration showed no significant increase in MCF-7 cell proliferation, compared to the control group. However, 10-6 M of ZP significantly reduced cell viability. The changes in gene expression slightly differed between the ZP and control groups. The in vivo and in vitro assays, together with gene expression analysis, demonstrated that ZP showed no significant estrogenic activity (6).

Molecular Formula: C₁₀H₈N₂O₂S₂Zn
Molecular Weight: 317.686 g/mol
CAS : 1121-31-9
Solubility in water: 8 ppm (pH 7)

Synonyms :

pyrithione zinc; bis(N-oxopyridine-2-thionato)zinc (II); de-squaman; zinc pyridinethione; zincpolyanemine; Zincon; Dan-Gard

References____________________

(1) Zinc Pyrithione: A Topical Antimicrobial With Complex Pharmaceutics.

Schwartz JR.

J Drugs Dermatol. 2016 Feb;15(2):140-4. Review

(2) Zinc in skin pathology and care.

Bibi Nitzan Y, Cohen AD. 

J Dermatolog Treat. 2006;17(4):205–210.

(3) Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases.
Zhao C, Chen X, Yang C, Zang D, Lan X, Liao S, Zhang P, Wu J, Li X, Liu N, Liao Y, Huang H, Shi X, Jiang L, Liu X, Dou QP, Wang X, Liu J.
Oncotarget. 2017 Feb 21;8(8):13942-13956. doi: 10.18632/oncotarget.14572. 

(4) Allergic contact dermatitis induced by zinc pyrithione in shampoo: a case report.

Hsieh CW, Tu ME, Wu YH.  Dermatol Sin. 2010;28(4):163–166.

(5) http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_133.pdf

(6) Estrogenic activity of zinc pyrithione: An in vivo and in vitro study.
Kwack SJ, Yoon KS, Youn NH, Gu HG.
Environ Health Toxicol. 2017 Feb 9. doi: 10.5620/eht.e2017004

 

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