Inhibitory effect of timolol on topical glucocorticoid‑induced skin telangiectasia

Li,Yan‑Fei; Chen,Xiao‑Yan; Lei,Tie‑Chi

doi:10.3892/mmr.2018.9266

Inhibitory effect of timolol on topical glucocorticoid‑induced skin telangiectasia

Authors:
- Yan‑Fei Li
- Xiao‑Yan Chen
- Tie‑Chi Lei
View Affiliations

Affiliations: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Pathology, Baotou Medical College, Baotou, Inner Mongolia Autonomous Region 014010, P.R. China
Published online on: July 9, 2018 https://doi.org/10.3892/mmr.2018.9266
Pages: 2823-2831
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study wasto investigate the potential inhibitory effect of timolol on topical glucocorticoid‑induced skin telangiectasia. In rabbits, flumethasone ointment was used to induce skin telangiectasia in the inner ear. Subsequently, timolol maleate (0.5%) eye drops (TMEDs) were administered twice daily for 4 weeks. Expression of the antibacterial peptides 37‑amino acid peptide (LL‑37) and kallikrein‑5 (KLK5) was detected using quantitative polymerase chain reaction (PCR) and semi‑quantitative reverse transcription‑PCR. In patients with facial skin telangiectasia, one cheek of each patient was assigned to a treatment group and the other to a control group. For the treatment group cheeks, topical application of TMEDs was combined with 0.1% tacrolimus ointment once or twice daily for 8 weeks. The control group cheeks were administered with 0.1% tacrolimus ointment alone. Alterations in lesions were recorded by dermoscopy, and the L, a and b values of lesions were measured, based on the Commission Internationale de l'Éclairage system, with a chromameter prior to and at 1, 2, 4 and 8 weeks following treatment. The results indicated that erythema, papules and telangiectasia were significantly diminished following 4 weeks of treatment with TMEDs in rabbits. Notably, the expression of LL‑37 and KLK5 mRNA was increased in the negative control group; however, it was decreased in the trial and blank groups. Clinical and dermoscopy images demonstrated that erythema was reduced in the 2 groups for 1 week, and that telangiectasia in the treatment group was markedly reduced compared with the control group at 4 weeks. The difference of the L and a values of lesions between the treatment and control group was significant (P<0.05). Overall, the present results suggested that the abnormal expression of LL‑37 may be one of the mechanisms underlying the pathogenesis of facial corticosteroid addiction dermatitis (FCAD) and TMEDs may inhibit the mRNA expression of LL‑37 by downregulating KLK5; in this regard, TMEDs may serve a role in attenuating telangiectasia, which may be beneficial in improving the telangiectasia symptoms of FCAD.

View Figures

View References

1	Hajar T, Leshem YA, Hanifin JM, Nedorost ST, Lio PA, Paller AS, Block J and Simpson EL: (The National Eczema Association Task Force): A systematic review of topical corticosteroid withdrawal (‘steroid addiction’) in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol. 72(541–549): e22015.
2	Ghosh A, Sengupta S, Coondoo A and Jana AK: Topical corticosteroid addiction and phobia. Indian J Dermatol. 59:465–468. 2014. View Article : Google Scholar : PubMed/NCBI
3	Sheary B: Topical corticosteroid addiction and withdrawal-An overview for GPs. Aust Fam Physician. 45:386–388. 2016.PubMed/NCBI
4	Luan Q, Liu L, Wei Q and Liu B: Effects of low-level light therapy on facial corticosteroid addiction dermatitis: A retrospective analysis of 170 Asian patients. Indian J Dermatol Venereol Leprol. 80:1942014. View Article : Google Scholar : PubMed/NCBI
5	Lu H, Xiao T, Lu B, Dong D, Yu D, Wei H and Chen HD: Facial corticosteroid addictive dermatitis in Guiyang City, China. Clin Exp Dermatol. 35:618–621. 2010. View Article : Google Scholar : PubMed/NCBI
6	Goldman D: Tacrolimus ointment for the treatment of steroid-induced rosacea: A preliminary report. J Am Acad Dermatol. 44:995–998. 2001. View Article : Google Scholar : PubMed/NCBI
7	Rapaport MJ and Lebwohl M: Corticosteroid addiction and withdrawal in the atopic: The red burning skin syndrome. Clin Dermatol. 21:201–214. 2003. View Article : Google Scholar : PubMed/NCBI
8	Sharifi M, Koch JM, Steele RJ, Adler D, Pompili VJ and Sopko J: Third degree AC block due to ophthalmic timilol solution. Int J Cardiol. 80:257–259. 2001. View Article : Google Scholar : PubMed/NCBI
9	Ng MSY, Tay YK, Ng SS, Foong AYW and Koh MJ: Comparison of two formulations of topical timolol for the treatment of infantile hemangiomas. Pediatr Dermatol. 34:492–493. 2017. View Article : Google Scholar : PubMed/NCBI
10	Sushma NJ, Priyanka S and Rao J: Neuroprotective role of melantonin against aluminum-induced oxidative stress in the hippocampus of mouse brain. J Appl Pharm Sci. 1:126–133. 2011.
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
12	Chinese Medical Association dermatology branch beauty professional group: Diagnosis and treatment guidelines of Corticosteroid addictive dermatitis. J Clin Dermatol. 38:549–550. 2009.
13	Jost S, Cauwerts C and Avouac P: CIE 2017 color fidelity index Rf: A better index to predict perceived color difference? J Opt Soc Am A Opt Image Sci Vis. 35:B202–B213. 2018. View Article : Google Scholar : PubMed/NCBI
14	Barnes L, Kaya G and Rollason V: Topical corticosteroid-induced skin atrophy: A comprehensive review. Drug Saf. 38:493–509. 2015. View Article : Google Scholar : PubMed/NCBI
15	Inoue Y, Isobe M, Shiohara T and Hayashi H: Inhibitory activity of CX-659S, a novel diaminouracil derivative, against the rebound phenomenon following withdrawal of corticosteroid therapy for chronic contact hypersensitivity responses. Int Arch Allergy Immunol. 131:143–152. 2003. View Article : Google Scholar : PubMed/NCBI
16	Slominski AT, Manna PR and Tuckey RC: On the role of skin in the regulation of local and systemic steroidogenic activities. Steroids. 103:72–88. 2015. View Article : Google Scholar : PubMed/NCBI
17	Xiao Y and Wang J: Progress on the study of corticosteroid addictive dermatitis. J Yunnan Med. 35:380–382. 2014.(In Chinese).
18	Sari E, Bakar B, Dincel GC and Yildiran Budak FA: Effects of DMSO on a rabbit ear hypertrophic scar model: A controlled randomized experimental study. J Plast Reconstr Aesthet Surg. 70:509–517. 2017. View Article : Google Scholar : PubMed/NCBI
19	Nicoli S, Padula C, Aversa V, Vietti B, Wertz PW, Millet A, Falson F, Govoni P and Santi P: Characterization of rabbit ear skin as a skin model for in vitro transdermal permeation experiments: Histology, lipid composition and permeability. Skin Pharmacol Physiol. 21:218–226. 2008. View Article : Google Scholar : PubMed/NCBI
20	Hu L, Huang HZ, Li X, Lin XX and Li W: Open-label nonrandomized left-right comparison of imiquimod 5% ointment and timolol maleate 0.5% eye drops in the treatment of proliferating superficial infantile hemangioma. Dermatology. 230:150–155. 2015. View Article : Google Scholar : PubMed/NCBI
21	Bhat YJ, Yaseen A and Hassan I: Topical timolol maleate: An effectual and safe recourse for infantile hemangiomas. Indian Dermatol Online J. 7:124–125. 2016. View Article : Google Scholar : PubMed/NCBI
22	Aoki M, Akaishi S, Nakao J, Dohi T, Hyakusoku H and Ogawa R: Objective spectrometric measurement of keloid color in the East Asian population: Pitfalls of subjective color measurements. J Nippon Med Sch. 83:142–149. 2016. View Article : Google Scholar : PubMed/NCBI
23	Takiwaki H, Miyaoka Y, Kohno H and Arase S: Graphic analysis of the relationship between skin colour change and variations in the amounts of melanin and haemoglobin. Skin Res Technol. 8:78–83. 2002. View Article : Google Scholar : PubMed/NCBI
24	de Menonville Thibaut S, Rosignoli C, Soares E, Roquet M, Bertino B, Chappuis JP, Defoin-Platel/Chaussade C and Piwnica D: Topical Treatment of Rosacea with Ivermectin Inhibits Gene Expression of Cathelicidin Innate Immune Mediators, LL-37 and KLK5, in reconstructed and ex vivo skin models. Dermatol Ther (Heidelb). 7:213–225. 2017. View Article : Google Scholar : PubMed/NCBI
25	Marcinkiewicz M and Majewski S: The role of antimicrobial peptides in chronic inflammatory skin diseases. Postepy Dermatol Alergol. 33:6–12. 2016. View Article : Google Scholar : PubMed/NCBI
26	Takahashi T and Gallo RL: The critical and multifunctional roles of antimicrobial peptides in dermatology. Dermatol Clin. 35:39–50. 2017. View Article : Google Scholar : PubMed/NCBI
27	Sakabe J, Umayahara T, Hiroike M, Shimauchi T, Ito T and Tokura Y: Calcipotriol increases hCAP18 mRNA expression but inhibits extracellular LL37 peptide production in IL17/IL22-stimulated normal human epidermal keratinocytes. Acta Derm Venereol. 94:512–516. 2014. View Article : Google Scholar : PubMed/NCBI
28	Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, Dorschner RA, Bonnart C, Descargues P, Hovnanian A, et al: Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 13:975–980. 2007. View Article : Google Scholar : PubMed/NCBI
29	Bandurska K, Berdowska A, Barczyńska-Felusiak R and Krupa P: Unique features of human cathelicidin LL-37. Biofactors. 41:289–300. 2015. View Article : Google Scholar : PubMed/NCBI