The effect of zinc in the form of erythromycin-zinc complex (ZinerytR lotion) and zinc acetate on metallothionein expression and distribution in hamster skin

Abstract

The occurrence of zinc-induced synthesis of metallothionein in skin after topical application of the anti-acne drug Zineryt lotion was investigated in hamster ears. The dinitrophenyl hapten-sandwich immunohistochemical method involving a monoclonal anti-metallothionein (MT) antibody (E9) was used to detect and localize zinc-binding MT in the 'treated' and untreated hamster skin. Atomic absorption spectrophotometry and dithizone histochemistry indicated that zinc penetrated the skin more readily, and accumulated more efficiently within the sebaceous glands, when applied to the skin surface as the organo-zinc complex, rather than as the inorganic zinc salt. MT and zinc had similar distributions in hamster skin exposed to the metal. Thus, MT immunoreactivity was especially intense in the sebaceous glands of Zineryt lotion-treated skin, with evidence of nuclear distribution in some cells. Zinc delivered to the sebaceous glands, and released from the organo-complex under the prevailing aqueous conditions, certainly induced MT synthesis; the cysteine-rich protein may protect the pilosebaceous units during the inflammatory phase of acne by scavenging generated oxyradical species.

Zinc and Skin Health

“…Zinc may also have direct activity, inhibiting bacterial lipases from converting sebum triglycerides to fatty acids, which are presumably more potent mediators of acne 106 . The zinc delivered in this way was found to be bioavailable to the point of stimulating the production of MT, which may result in the indirect benefits of the antioxidative activity of this protein 107 . Comparison of the zinc‐containing antibiotic treatment with one without zinc (although also a lower antibiotic level) demonstrated the zinc‐containing product to have greater lesion reduction efficacy 108 …”

A double-blind controlled evaluation of the sebosuppressive activity of topical erythromycin-zinc complex

“…Of these, the combination of 4% erythromycin with 1.2% zinc acetate has proved its efficacy [3,4]. The beneficial effect of the zinc supplementation has been ascribed to four mechanisms including: (a) modulation of epithelial differentiation, either directly or through the vitamin A retinol-binding protein metabolism; (b) anti-inflammatory effects; (c) antibacterial effects; and (d) anti-androgen activity [5][6][7][8][9]. As zinc may inhibit 5 c~-reductase activity [10,11], which is mostly present in sebaceous glands [12], it has been postulated that sebosuppressive activity could be expected with topical zinc therapy as the zinc molecule is known to be readily absorbed through the pilosebaceous apparatus [9].…”

“…The beneficial effect of the zinc supplementation has been ascribed to four mechanisms including: (a) modulation of epithelial differentiation, either directly or through the vitamin A retinol-binding protein metabolism; (b) anti-inflammatory effects; (c) antibacterial effects; and (d) anti-androgen activity [5][6][7][8][9]. As zinc may inhibit 5 c~-reductase activity [10,11], which is mostly present in sebaceous glands [12], it has been postulated that sebosuppressive activity could be expected with topical zinc therapy as the zinc molecule is known to be readily absorbed through the pilosebaceous apparatus [9].In a first pilot study [13] with five volunteers, topical applications of a lotion containing an erythromycinzinc complex appeared to reduce significantly the sebum delivery after 9 weeks of application when compared to an untreated site. As the effect on sebum excretion could be due to the zinc contained in the preparation, a comparison with a 4% erythromycin preparation has now been investigated in order to confirm this assumption.…”

The Increasing Importance of the Hair Follicle Route in Dermal and Transdermal Drug Delivery

“…It was suggested that by increasing the distribution of corresponding drugs in the sebaceous gland, the therapeutic effectivity could be signifi cantly improved (Rolland et al 1993 ). Respective efforts have already been made (Morgan et al 1993 ;Ridolfi et al 2012 ;Rolland et al 1993 ), and some promising antiacne products are already on the market. The multipotent, highly proliferative, and easily accessible stem cells located in the bulge region (Ohyama 2007 ) are also to be integrated in the therapeutic concepts for cutaneous regenerative medicine or gene correction of congenital hair disorders or genetic skin diseases.…”