Protective Effect of Dermal Brimonidine Applications Against UV Radiation‐induced Skin Tumors, Epidermal Hyperplasia and Cell Proliferation in the Skin of Hairless Mice

Abstract

Brimonidine at 0.18%, 1% and 2% concentrations applied topically in hairless mice significantly decreased tumor burden and incidences of erythema, flaking, wrinkling and skin thickening induced by UVR. The unbiased median week to tumor ≥1 mm was increased by the 1% and 2% concentrations. The tumor yield was reduced by all concentrations at week 40 for all tumor sizes but the ≥4 mm tumors with the 0.18% concentration. At week 52, the tumor yield was reduced for all tumor sizes and all brimonidine concentrations. The tumor incidence was reduced by all concentrations at week 40 for all tumor sizes, but the ≥4 mm tumor with the 0.18% concentration and at week 52 for all tumor sizes with the 1% and 2% concentrations and with the 0.18% concentration only for the ≥4 mm tumors. Reductions in ≥4 mm tumor incidences compared to the vehicle control group were 54%, 91% and 86% by week 52 for the 0.18%, 1% and 2% concentrations, respectively. Brimonidine at 2% applied 1 h before or just after UVB irradiation on hairless mice decreased epidermal hyperplasia by 23% and 32% and epithelial cell proliferation by 59% and 64%, respectively, similar to an epidermal growth factor receptor (EGFR) inhibitor.

Topical Brimonidine Delays Ultraviolet Radiation‐Induced Squamous Cell Carcinoma in Hairless Mice

“…Therefore, the delay in SCC development observed in the mice administered 1% topical brimonidine cream before UVR exposure was most likely caused by a UVR absorption by the drug. Brimonidine can absorb light in the UVB wavelength range (280-315 nm), as shown by Bouvier et al (12). However, there can be multiple reasons for a delay in photocarcinogenesis.…”

“…However, we have previously investigated the same vehicle used in groups 1, 3 and 5 and it did not alter the time to tumor development or induce erythema in the same strain of mice. However, Bouvier et al (12) demonstrated that the commercial gel-formulation vehicle alone did not influence the carcinogenic response compared to UVR treatment in the absence of gel. Other studies, such as that by Fowler et al (6), evaluated the optimal concentration, efficacy and safety of brimonidine gel for treating erythema in patients with rosacea and showed that the vehicle formulation did not aggravate erythema or other diseases.…”

“…Ultraviolet radiation (UVR) exposure is responsible for approximately 90% of keratinocyte skin cancers, which include squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) (11). Bouvier et al (12) investigated the anticarcinogenic potential of different concentrations of brimonidine (0.18%, 1% and 2%) on hairless mice exposed to UVR and showed that brimonidine delayed tumor development. Brimonidine was applied before UVR exposure on 3 days and after UVR exposure on a further 2 days per week for 1 year (12).…”

“…Bouvier et al (12) investigated the anticarcinogenic potential of different concentrations of brimonidine (0.18%, 1% and 2%) on hairless mice exposed to UVR and showed that brimonidine delayed tumor development. Brimonidine was applied before UVR exposure on 3 days and after UVR exposure on a further 2 days per week for 1 year (12). There are many patients using brimonidine on UVR-exposed areas for years.…”

Brimonidine gel for the treatment of recalcitrant facial erythema in diseases other than rosacea: a novel tool for clinicians

“…Topical 2% of brimonidine applied 1 h before or just after UVB irradiation on hairless mice has shown protective effect against UV radiation-induced skin tumours, epidermal hyperplasia and cell proliferation, partly making an interesting use in patients with lupus and dermatomyositis. 7 We have been using topical brimonidine in other patients with heliotrope rash, but it has not always worked due to patient's intolerance or lack of efficacy.…”