Zinc pyrithione (Zinc Omadine®) allergy

Brandrup, Flemming; Menné, Torkil

doi:10.1111/j.1600-0536.1985.tb01041.x

Cited by 24 publications

(11 citation statements)

References 5 publications

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“…ZnPT is a widely-used cutaneous microbicidal OTC-drug (Pierard-Franchimont et al 2002; Bailey et al 2003; Smegal et al 2004; Guthery et al 2005), and topical safety and toxicity profile of ZnPT have been studied to some extent previously (Snyder et al 1965; Brandrup and Menne 1985). However, cytotoxic and genotoxic effects of ZnPT have been substantiated in mouse lymphoma cells and teratogenicity was described in zebra fish (Goka 1999; Moller et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis

Lamore

Wondrak

2011

Biometals

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Zinc ion homeostasis plays an important role in human cutaneous biology where it is involved in epidermal differentiation and barrier function, inflammatory and antimicrobial regulation, and wound healing. Zinc-based compounds designed for topical delivery therefore represent an important class of cutaneous therapeutics. Zinc pyrithione (ZnPT) is an FDA-approved microbicidal agent used worldwide in over-the-counter topical antimicrobials, and has also been examined as an investigational therapeutic targeting psoriasis and UVB-induced epidermal hyperplasia. Recently, we have demonstrated that cultured primary human skin keratinocytes display an exquisite sensitivity to nanomolar ZnPT concentrations causing induction of heat shock response gene expression and poly(ADP-ribose) polymerase (PARP)-dependent cell death (Cell Stress Chaperones 15:309–322, 2010). Here we demonstrate that ZnPT causes rapid accumulation of intracellular zinc in primary keratinocytes as observed by quantitative fluorescence microscopy and inductively coupled plasma mass spectrometry (ICP-MS), and that PARP activation, energy crisis, and genomic impairment are all antagonized by zinc chelation. In epidermal reconstructs (EpiDerm™) exposed to topical ZnPT (0.1–2% in Vanicream™), ICP-MS demonstrated rapid zinc accumulation, and expression array analysis demonstrated upregulation of stress response genes encoding metallothionein-2A (MT2A), heat shock proteins (HSPA6, HSPA1A, HSPB5, HSPA1L, DNAJA1, HSPH1, HSPD1, HSPE1), antioxidants (SOD2, GSTM3, HMOX1), and the cell cycle inhibitor p21 (CDKN1A). IHC analysis of ZnPT-treated EpiDerm™ confirmed upregulation of Hsp70 and TUNEL-positivity. Taken together our data demonstrate that ZnPT impairs zinc ion homeostasis and upregulates stress response gene expression in primary keratinocytes and reconstructed human epidermis, activities that may underlie therapeutic and toxicological effects of this topical drug.

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Section: Discussionmentioning

confidence: 99%

Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis

Lamore

Wondrak

2011

Biometals

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“…Diazolidinyl urea allergy (6) and allergy to phenoxyethanol (7) have been reported only once, whereas allergic reactions to zinc pyrithione (8,9) and dichlorophene (9, IO) have been described several times.…”

Section: Discussionmentioning

confidence: 99%

Contact allergy to preservatives – II

et al. 1986

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To determine whether the prevalence of allergic reactions to certain preservatives warrants their inclusion in a routine series for patch testing, a tray of 14 preservatives was tested in 501 consecutive suspected contact dermatitis patients. More than 1% positive reactions were found with DMDM hydantoin, Kathon CG, and alkyl trimethyl ammonium chloride only. The concentration of alkyl trimethyl ammonium chloride (0.1% aqua) was considered too high. Of 6 patients reacting to the formaldehyde releaser DMDM hydantoin, 4 were positive to formaldehyde. Kathon CG may be an important allergen in the Netherlands, and it is worthwhile for dermatologists there to add it to the standard test series. The recent inclusion of quaternium-15 in the ICDRG standard series appears to be of little value to them.

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“…Epidermal deposition and retention of the lipophilic metal chelate ZnPT following topical application has been demonstrated in human skin (Rutherford and Black 1969;Leyden et al 1979), and percutaneous penetration of ZnPT through rat, rabbit, guinea pig, and rhesus monkey skin has been documented earlier (Okamoto et al 1967;Howes and Black 1975;Gibson and Calvin 1978;Guthery et al 2005). Topical safety and toxicity profile of this OTC-drug have been studied to some extent previously, and it has been established that ZnPT does not display a potential for primary irritation or sensitization of human skin (Snyder et al 1965;Brandrup and Menne 1985;Skoulis et al 1993).…”

Section: Introductionmentioning

confidence: 98%

The topical antimicrobial zinc pyrithione is a heat shock response inducer that causes DNA damage and PARP-dependent energy crisis in human skin cells

Lamore

Cabello

Wondrak

2010

Cell Stress and Chaperones

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The differentiated epidermis of human skin serves as an essential barrier against environmental insults from physical, chemical, and biological sources. Zinc pyrithione (ZnPT) is an FDA-approved microbicidal agent used worldwide in clinical antiseptic products, over-thecounter topical antimicrobials, and cosmetic consumer products including antidandruff shampoos. Here we demonstrate for the first time that cultured primary human skin keratinocytes and melanocytes display an exquisite vulnerability to nanomolar concentrations of ZnPT resulting in pronounced induction of heat shock response gene expression and impaired genomic integrity. In keratinocytes treated with nanomolar concentrations of ZnPT, expression array analysis revealed massive upregulation of genes encoding heat shock proteins (HSPA6, HSPA1A, HSPB5, HMOX1, HSPA1L, and DNAJA1) further confirmed by immunodetection. Moreover, ZnPT treatment induced rapid depletion of cellular ATP levels and formation of poly (ADP-ribose) polymers. Consistent with an involvement of poly(ADP-ribose) polymerase (PARP) in ZnPT-induced energy crisis, ATP depletion could be antagonized by pharmacological inhibition of PARP. This result was independently confirmed using PARP-1 knockout mouse embryonic fibroblasts that were resistant to ATP depletion and cytotoxicity resulting from ZnPT exposure. In keratinocytes and melanocytes, single-cell gel electrophoresis and flow cytometric detection of γ-H2A.X revealed rapid induction of DNA damage in response to ZnPT detectable before general loss of cell viability occurred through caspase-independent pathways. Combined with earlier experimental evidence that documents penetration of ZnPT through mammalian skin, our findings raise the possibility that this topical antimicrobial may target and compromise keratinocytes and melanocytes in intact human skin.

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Zinc pyrithione (Zinc Omadine®) allergy

Cited by 24 publications

References 5 publications

Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis

Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis

Contact allergy to preservatives – II

The topical antimicrobial zinc pyrithione is a heat shock response inducer that causes DNA damage and PARP-dependent energy crisis in human skin cells

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