Ameliorative Effect of Topical Clinoptilolite on 2,4- Dinitrof luorobenzene Induced Atopic Dermatitis Model in Mice

Year 2024, Volume: 43 Issue: 2, 93 - 101, 31.12.2024

Büşra Gülbenli Türkoğlu , Metin Koray Albay , Volkan İpek

https://doi.org/10.30782/jrvm.1401217

Abstract

Atopic dermatitis is a multifactorial disease process. It is defined as "a genetically predisposed inflammatory and itchy allergic skin disease associated with the production of immunoglobulin E against environmental allergens". Experimental models are considered important in the evaluation of therapeutic agents for the treatment of atopic dermatitis. This study aimed to reveal the effects of clinoptilolite and tacrolimus on atopic
dermatitis lesions in the atopic dermatitis model in mice induced with 2,4-dinitrofluorobenzene. For inducing the atopic dermatitis model, mice were administered topically on the back with 0.15% 2,4-dinitrofluorobenzene twice a week for 5 weeks. For the next 4 weeks, 0.15% 2,4-dinitrofluorobenzene was applied once a week to maintain inflammation. Afterward, topical tacrolimus cream (0.1%) and topical clinoptilolite powder
were used for 4 weeks. Clinical score, serum thymus and activation-regulated chemokine, histopathology, and thymic stromal lymphopoietin (TSLP) immunostainings were evaluated between groups. While clinoptilolite treatment was found to be effective in the normalization of clinical scores, serum thymus and activation regulated chemokine levels were found to be variable and insignificant. Histopathologically, clinoptilolite
had an ameliorative effect on epidermal thickness and inflammation yet there was no significant difference of mast cells and fibrosis between groups. Furthermore, clinoptilolite had an inhibitory effect of TSLP immunostaining on epidermal tissue. In conclusion, clinoptilolite could be an alternative treatment of atopic dermatitis with its effects similar to tacrolimus.

Keywords

Atopic dermatitis, clinoptilolite, tacrolimus, TARC, TSLP

Ethical Statement

Before the study, the ethics committee approval was obtained of Burdur Mehmet Akif Ersoy University Experimental Animals Local Ethics Committee (17.02.2021; decision number:727).

Supporting Institution

Burdur Mehmet Akif Ersoy University Scientific Research Projects Coordinatorship

Project Number

0668-YL-20

Thanks

This research was supported by the “Burdur Mehmet Akif Ersoy University Scientific Research Projects Coordinatorship” with the project 0668-YL-20.

References

• 1. Siegels D, Heratizadeh A, Abraham S, Binnmyr J, Brockow K, Irvine AD, Halken S, Mortz CG, Flohr C, Schmid-Grendelmeier P, Van der Poel LA, Muraro A, Weidinger S, Werfel T, Schmitt J. Systemic treatments in the management of atopic dermatitis: A systematic review and meta-analysis. Allergy, 76(4):1053–1076, 2021.
• 2. Bieber T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov, 21(1):21–40, 2021.
• 3. Nakahara T, Kido-Nakahara M, Tsuji G, Furue M. Basics and recent advances in the pathophysiology of atopic dermatitis. J Dermatol, 48(2):130–139, 2021.
• 4. Choi JH, Kim HG, Jin SW, Han EH, Khanal T, Do MT, Hwang YP, Choi JM, Chun SS, Chung YC. Topical application of Pleurotus eryngii extracts inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice by the regulation of Th1/Th2 balance. Food Chem Toxicol, 53:38–45, 2013.
• 5. Shiohara T, Hayakawa J, Mizukawa Y. Animal models for atopic dermatitis: are they relevant to human disease? J Dermatol Sci, 36(1):1–9, 2004.
• 6. Yamashita H, Ito T, Kato H, Asai S, Tanaka H, Nagai H, Inagaki N. Comparison of the efficacy of tacrolimus and cyclosporine A in a murine model of dinitrofluorobenzene-induced atopic dermatitis. Eur J Pharmacol, 645(1–3):171–176, 2010.
• 7. Koch S. What Is New in the Diagnosis and Management of Canine Atopic Dermatitis. Today’s Vet Pract,(- May/June):95–102, 2015.
• 8. Gupta AK, Adamiak A, Chow M. Tacrolimus: a review of its use for the management of dermatoses. J Eur Acad Dermatol Venereol, 16(2):100–114, 2002.
• 9. Noguchi A, Tominaga M, Takahashi N, Matsuda H, Kamata Y, Umehara Y, Ko KC, Suga Y, Ogawa H, Takamori K. Differences in therapeutic effects of topically applied corticosteroid and tacrolimus on atopic dermatitis-like symptoms in NC/Nga mice. J Dermatol Sci, 86(1):54–62, 2017.
• 10. Bekersky I, Fitzsimmons W, Tanase A, Maher RM, Hodosh E, Lawrence I. Nonclinical and early clinical development of tacrolimus ointment for the treatment of atopic dermatitis. J Am Acad Dermatol, 44: 2001.
• 11. Hecht K. Clinoptilolite Zeolite as Sanogenetic Important for Human Health. Arch issues, 1:1–14, 2011.
• 12. Aksoy SÖ, Tunk CO, Sevinç Aİ, Durak MG. Effects of locally applied Clinoptilolite (Froximun®) on seroma formation in a rat mastectomy and axillary lymph node dissection model. Dokuz Eylül Üniversitesi Tıp Fakültesi Derg, 33(2):139–147, 2019.
• 13. Kitamura A, Takata R, Aizawa S, Watanabe H, Wada T. A murine model of atopic dermatitis can be generated by painting the dorsal skin with hapten twice 14 days apart. Sci Reports, 8(1):1–9, 2018.
• 14. Sozmen SC, Karaman M, Micili SC, Isik S, Ayyildiz ZA, Bagriyanik A, Uzuner N, Karaman O. Resveratrol ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesions through effects on the epithelium. PeerJ, 4(3), 2016.
• 15. Kim TH, Kim GD, Ahn HJ, Cho JJ, Park YS, Park CS. The inhibitory effect of naringenin on atopic dermatitis induced by DNFB in NC/Nga mice. Life Sci, 93(15):516–524, 2013.
• 16. Watanabe T, Hamada K, Tategaki A, Kishida H, Tanaka H, Kitano M, Miyamoto T. Oral administration of lactic acid bacteria isolated from traditional South Asian fermented milk “dahi” inhibits the development of atopic dermatitis in NC/Nga mice. J Nutr Sci Vitaminol (Tokyo), 55(3):271–278, 2009.
• 17. Izumi R, Azuma K, Izawa H, Morimoto M, Nagashima M, Osaki T, Tsuka T, Imagawa T, Ito N, Okamoto Y. Chitin nanofibrils suppress skin inflammation in atopic dermatitis-like skin lesions in NC/Nga mice. Carbohydr Polym, 146:320–327, 2016.
• 18. Choi YY, Kim MH, Kim JH, Jung HS, Sohn Y, Choi YJ, Hwang MK, Kim SH, Kim J, Yang WM. Schizonepeta tenuifolia Inhibits the Development of Atopic Dermatitis in Mice. Phytother Res, 27(8):1131–1135, 2013.
• 19. Bonneville M, Chavagnac C, Vocanson M, Rozieres A, Benetiere J, Pernet I, Denis A, Nicolas JF, Hennino A. Skin contact irritation conditions the development and severity of allergic contact dermatitis. J Invest Dermatol, 127(6):1430–1435, 2007.
• 20. Tang L, Li X, Wan L, Wang H, Mai Q, Deng Z, Ding H. Ameliorative effect of orally administered different linoleic acid/α-linolenic acid ratios in a mouse model of DNFB-induced atopic dermatitis. J Funct Foods, 65:103754, 2020.
• 21. Choi JH, Jin SW, Lee GH, Cho SM, Jeong HG. Orostachys japonicus ethanol extract inhibits 2,4 dinitrochlorobenzene- induced atopic dermatitis-like skin lesions in NC/Nga mice and TNF-α/IFN-γ-induced TARC expression in HaCaT cells. Toxicol Res, 36(2):99–108, 2019.
• 22. Inagaki N, Shiraishi N, Igeta K, Itoh T, Chikumoto T, Nagao M, Kim JF, Nagai H. Inhibition of scratching behavior associated with allergic dermatitis in mice by tacrolimus, but not by dexamethasone. Eur J Pharmacol, 546(1 3):189–196, 2006.
• 23. Han NR, Moon PD, Kim HM, Jeong HJ. Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP. Arch Biochem Biophys, 542:14–20, 2014.
• 24. Lee JH, Shih YT, Wei ML, Sun CK, Chiang BL. Classification of established atopic dermatitis in children with the in vivo imaging methods. J Biophotonics, 12(5), 2019.
• 25. Jin H, He R, Oyoshi M, Geha RS. Animal models of atopic dermatitis. J Invest Dermatol, 129(1):31–40, 2009.
• 26. Uraloğlu M, Livaoğlu M, Ağdoğan Ö, Mungan S, Alhan E, Karaçal N. An evaluation of five different dressing materials on split-thickness skin graft donor site and full-thickness cutaneous wounds: an experimental study. Int Wound J, 11(1):85–92, 2014.
• 27. Şentürk Demirel D, Demirel R, Ketani A, Balcı K. Effects on Performance, Skin and Liver Histology of Different Clinoptilolite Levels in Rat Diets. Turkish J Agric - Food Sci Technol, 3(3):133–141, 2015.
• 28. Hubner P, Donati N, Quines LK de M, Tessaro IC, Marcilio NR. Gelatin-based films containing clinoptilolite- Ag for application as wound dressing. Mater Sci Eng C Mater Biol Appl, 107, 2020.
• 29. Rustin MHA. The safety of tacrolimus ointment for the treatment of atopic dermatitis: a review. Br J Dermatol, 157(5):861–873, 2007.
• 30. Indra AK. Epidermal TSLP: A trigger factor for pathogenesis of Atopic Dermatitis (AD). Expert Rev Proteomics, 10(4):309, 2013.
• 31. Yoou M Schook, Nam SY, Wan Yoon K, Jeong HJ, Kim HM. Bamboo salt suppresses skin inflammation in mice with 2,4-dinitrofluorobenzene-induced atopic dermatitis. Chin J Nat Med, 16(2):97–104, 2018.
• 32. Kakinuma T, Nakamura K, Wakugawa M, Mitsui H, Tada Y, Saeki H, Torii H, Asahina A, Onai N, Matsushima K, Tamaki K. Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity. J Allergy Clin Immunol, 107(3):535–541, 2001.
• 33. Saeki H, Tamaki K. Thymus and activation regulated chemokine (TARC)/CCL17 and skin diseases. J Dermatol Sci, 43(2):75–84, 2006.
• 34. Vestergaard C, Yoneyama H, Murai M, Nakamura K, Tamaki K, Terashima Y, Imai T, Yoshie O, Irimura T, Mizutani H, Matsushima K. Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis-like lesions. J Clin Invest, 104(8):1097–1105, 1999.
• 35. Thijs J, Krastev T, Weidinger S, Buckens CF, De Bruin- Weller M, Bruijnzeel-Koomen C, Flohr C, Hijnen D. Biomarkers for atopic dermatitis: A systematic review and meta-analysis. Curr Opin Allergy Clin Immunol, 15(5):453–460, 2015.
• 36. Lim JM, Lee B, Min JH, Kim EY, Kim JH, Hong SY, Kim JJ, Sohn Y, Jung HS. Effect of peiminine on DNCB-induced atopic dermatitis by inhibiting inflammatory cytokine expression in vivo and in vitro. Int Immunopharmacol, 56:135–142, 2018.
• 37. Ngo HTT, Fang M, Hwang E, Kim Y, Park B, Seo SA, Do NQ, Nguyen QTN, Yi TH. Inhibitory Effects of Urtica thunbergiana Ethanol Extract on Atopic Dermatitis- Induced NC/Nga Mice. Antioxidants, 9(3), 2020.
• 38. Himadri, George R, Mathew L, Shanmugam V, Mani T, Jeyaseelan L. The role of thymus and activation regulated chemokine as a marker of severity of atopic dermatitis. J Am Acad Dermatol, 84(2):545–547, 2021.
• 39. Aw D, Silva AB, Maddick M, von Zglinicki T, Palmer DB. Architectural changes in the thymus of aging mice. Aging Cell, 7(2):158–167, 2008.