Ann Dermatol.  2016 Dec;28(6):690-696. 10.5021/ad.2016.28.6.690.

Application of Topical Acids Improves Atopic Dermatitis in Murine Model by Enhancement of Skin Barrier Functions Regardless of the Origin of Acids

Affiliations
  • 1Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea. choieh@yonsei.ac.kr

Abstract

BACKGROUND
The acidic pH of the stratum corneum (SC) is important for epidermal permeability barrier homeostasis. Acidification of the skin surface has been suggested as a therapeutic strategy for skin disorders such as atopic dermatitis (AD).
OBJECTIVE
We performed an animal study to evaluate the usefulness of acidification of SC for inhibition of AD lesions and to find out if the therapeutic effect of vinegar is attributable to its herbal contents, rather than its acidity.
METHODS
Five groups of six oxazolone-treated (Ox)-AD mice were treated for three weeks with creams of different acidity: vehicle cream alone (pH 5.5), neutralized vinegar cream (pH 7.4), pH 5.0 vinegar cream, pH 3.5 vinegar cream, and pH 3.5 hydrogen chloride (HCl) cream. Also, we have compared two groups of Ox-AD mice treated with pH 5.5 vehicle cream or pH 5.5 vinegar cream.
RESULTS
Ox-AD mice treated with acidic creams exhibited fewer AD-like lesions, had significantly lower eczema scores, decreased basal by transepidermal water loss (TEWL), and increased SC hydration compared to the groups given only vehicle and neutral cream. There was no significant difference between the acidic vinegar and HCl groups. Between the groups treated with vehicle and pH 5.5 vinegar cream, there was no difference in eczema score, basal TEWL and SC hydration.
CONCLUSION
Application of topical acids, regardless of their source materials, inhibits the development of AD lesions by maintenance of skin surface pH and skin barrier function in murine model.

Keyword

Atopic dermatitis; Skin barrier; Skin pH; Topical acid; Vinegar

MeSH Terms

Acetic Acid
Animals
Dermatitis, Atopic*
Eczema
Homeostasis
Hydrochloric Acid
Hydrogen-Ion Concentration
Mice
Permeability
Skin*
Water
Acetic Acid
Hydrochloric Acid
Water

Figure

  • Fig. 1 (A) Oxazolone-treated atopic dermatitis (Ox-AD) mice groups treated with pH 3.5 vinegar cream, pH 5.0 vinegar cream, or pH 3.5 hydrogen chloride (HCl) cream exhibited fewer AD-like lesions than mice treated with only vehicle cream (pH 5.5) or neutralized vinegar cream (pH 7.4). (B) Eczema scores were significantly higher in the vehicle group than in the acidic cream treatment groups. There was no difference in the eczema scores between vehicle group and neutralized vinegar cream treated group. Eczema scores were determined by the sum of the severity of erythema, edema, and lichenification. Severity: absent (0), mild (1), moderate (2), and severe (3). Results are shown as the mean±standard error of the mean. **p<0.05, ***p<0.001.

  • Fig. 2 (A, B) Significant decreases in basal transepidermal water loss (TEWL) and significant increases in stratum corneum (SC) hydration were observed in the mouse groups treated with pH 3.5 hydrogen chloride (HCl) cream or pH 3.5 and 5.0 vinegar creams compared with vehicle (veh.) or neutralized vinegar (neut vin.) cream. No significant differences were seen between the acidic vinegar-treated and HCl-treated group. Results are shown as the mean±standard error of the mean.

  • Fig. 3 (A) Eczema scores and (B) skin permeability barrier functions of Ox induced AD model mice after application of vehicle and pH 5.5 vinegar creams. Ox: oxazolone-treated, AD: atopic dermatitis, TEWL: transepidermal water loss, SC: stratum corneum.

  • Fig. 4 Maintenance of acidic pH after application of pH 3.5 vinegar, pH 3.5 hydrogen chloride (HCl) and pH 5.0 vinegar cream. Immediately after application of acidic cream, the skin surface pH decreased in pH 3.5 vinegar cream and HCl cream but not in pH 5.0 vinegar cream. Although pH rised after 15 minutes, the slope of increase was gentle, therefore low pH was maintained throughout 6 hours after application of acidic creams.


Reference

1. Hachem JP, Crumrine D, Fluhr J, Brown BE, Feingold KR, Elias PM. pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. J Invest Dermatol. 2003; 121:345–353.
Article
2. Mauro T, Holleran WM, Grayson S, Gao WN, Man MQ, Kriehuber E, et al. Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing. Arch Dermatol Res. 1998; 290:215–222.
Article
3. Fluhr JW, Kao J, Jain M, Ahn SK, Feingold KR, Elias PM. Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity. J Invest Dermatol. 2001; 117:44–51.
Article
4. Devillers AC, de Waard-van der Spek FB, Mulder PG, Oranje AP. Treatment of refractory atopic dermatitis using ‘wet-wrap’ dressings and diluted corticosteroids: results of standardized treatment in both children and adults. Dermatology. 2002; 204:50–55.
Article
Korting HC., Hübner K., Greiner K., Hamm G., Braun-Falco O. Differences in the skin surface pH and bacterial microflora due to the long-term application of synthetic detergent preparations of pH 5.5 and pH 7.0. Results of a crossover trial in healthy volunteers. Acta Derm Venereol. 1990. 70:429–431.
6. Elias PM. The skin barrier as an innate immune element. Semin Immunopathol. 2007; 29:3–14.
Article
7. Hachem JP, Behne M, Fluhr J, Feingold KR, Elias PM. Increased stratum corneum pH promotes activation and release of primary cytokine from the stratum corneum attributable to activation of serine proteases. J Invest Dermatol. 2002; 119:258.
8. Behne MJ, Meyer JW, Hanson KM, Barry NP, Murata S, Crumrine D, et al. NHE regulates the stratum corneum permeability barrier homeostasis. Microenvironment acidification assessed with fluorescence lifetime imaging. J Biol Chem. 2002; 277:47399–47406.
9. Mao-Qiang M, Jain M, Feingold KR, Elias PM. Secretory phospholipase A2 activity is required for permeability barrier homeostasis. J Invest Dermatol. 1996; 106:57–63.
Article
10. Mazereeuw-Hautier J, Redoules D, Tarroux R, Charveron M, Salles JP, Simon MF, et al. Identification of pancreatic type I secreted phospholipase A2 in human epidermis and its determination by tape stripping. Br J Dermatol. 2000; 142:424–431.
Article
11. Krien PM, Kermici M. Evidence for the existence of a self-regulated enzymatic process within the human stratum corneum -an unexpected role for urocanic acid. J Invest Dermatol. 2000; 115:414–420.
Article
12. Behne MJ, Barry NP, Hanson KM, Aronchik I, Clegg RW, Gratton E, et al. Neonatal development of the stratum corneum pH gradient: localization and mechanisms leading to emergence of optimal barrier function. J Invest Dermatol. 2003; 120:998–1006.
Article
13. Fluhr JW, Behne MJ, Brown BE, Moskowitz DG, Selden C, Mao-Qiang M, et al. Stratum corneum acidification in neonatal skin: secretory phospholipase A2 and the sodium/hydrogen antiporter-1 acidify neonatal rat stratum corneum. J Invest Dermatol. 2004; 122:320–329.
Article
14. Choi EH, Man MQ, Xu P, Xin S, Liu Z, Crumrine DA, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol. 2007; 127:2847–2856.
Article
15. Fluhr JW, Elias PM. Stratum corneum pH: formation and function of the ‘acid mantle’. Exog Dermatol. 2002; 1:163–175.
Article
16. Hatano Y, Man MQ, Uchida Y, Crumrine D, Scharschmidt TC, Kim EG, et al. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis. J Invest Dermatol. 2009; 129:1824–1835.
Article
17. Hachem JP, Roelandt T, Schürer N, Pu X, Fluhr J, Giddelo C, et al. Acute acidification of stratum corneum membrane domains using polyhydroxyl acids improves lipid processing and inhibits degradation of corneodesmosomes. J Invest Dermatol. 2010; 130:500–510.
Article
18. Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown BE, Rogiers V, et al. Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. J Invest Dermatol. 2005; 125:510–520.
Article
19. Holleran WM, Takagi Y, Uchida Y. Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett. 2006; 580:5456–5466.
Article
20. Hachem JP, Houben E, Crumrine D, Man MQ, Schurer N, Roelandt T, et al. Serine protease signaling of epidermal permeability barrier homeostasis. J Invest Dermatol. 2006; 126:2074–2086.
Article
21. Lee HJ, Lee NR, Jung M, Kim DH, Choi EH. Atopic march from atopic dermatitis to asthma-like lesions in NC/Nga mice is accelerated or aggravated by neutralization of stratum corneum but partially inhibited by acidification. J Invest Dermatol. 2015; 135:3025–3033.
Article
22. Lee HJ, Yoon NY, Lee NR, Jung M, Kim DH, Choi EH. Topical acidic cream prevents the development of atopic dermatitis- and asthma-like lesions in murine model. Exp Dermatol. 2014; 23:736–741.
Article
23. Lee NR, Lee HJ, Yoon NY, Kim D, Jung M, Choi EH. Acidic water bathing could be a safe and effective therapeutic modality for severe and refractory atopic dermatitis. Ann Dermatol. 2016; 28:126–129.
Article
24. Lee HJ, Jung M, Kim JH, Yoon NY, Choi EH. The effect of adipose-derived stem cell-cultured media on oxazolone treated atopic dermatitis-like murine model. Ann Dermatol. 2012; 24:181–188.
Article
25. Man MQ, Hatano Y, Lee SH, Man M, Chang S, Feingold KR, et al. Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. J Invest Dermatol. 2008; 128:79–86.
Article
26. Suto H, Matsuda H, Mitsuishi K, Hira K, Uchida T, Unno T, et al. NC/Nga mice: a mouse model for atopic dermatitis. Int Arch Allergy Immunol. 1999; 120:Suppl 1. 70–75.
Article
27. Yang F, Tanaka M, Wataya-Kaneda M, Yang L, Nakamura A, Matsumoto S, et al. Topical application of rapamycin ointment ameliorates Dermatophagoides farina body extract-induced atopic dermatitis in NC/Nga mice. Exp Dermatol. 2014; 23:568–572.
Article
28. Elias PM. Stratum corneum defensive functions: an integrated view. J Invest Dermatol. 2005; 125:183–200.
Article
29. Fluhr JW, Mao-Qiang M, Brown BE, Hachem JP, Moskowitz DG, Demerjian M, et al. Functional consequences of a neutral pH in neonatal rat stratum corneum. J Invest Dermatol. 2004; 123:140–151.
Article
30. Yoon NY, Jung My, Kim DH, Lee HJ, Choi EH. Topical glucocorticoid or pimecrolimus treatment suppresses thymic stromal lymphopoietin-related allergic inflammatory mechanism in an oxazolone-induced atopic dermatitis murine model. Arch Dermatol Res. 2015; 307:569–581.
Article
31. Korting HC, Megele M, Mehringer L, Vieluf D, Zienicke H, Hamm G, et al. Influence of skin cleansing preparation acidity on skin surface properties. Int J Cosmet Sci. 1991; 13:91–102.
Article
32. Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Acta Derm Venereol. 2013; 93:261–267.
Article
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