Repeated Treatments with Ingenol Mebutate Prevents Progression of UV-Induced Photodamage in Hairless MiceReportar como inadecuado




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Background and Aim

Ingenol mebutate IngMeb is an effective treatment for actinic keratosis. In this study, we hypothesized that repeated treatments with IngMeb may prevent progression of UV-induced photodamage, and that concurrent application of a corticosteroid may reduce IngMeb-induced local skin responses LSR.

Methods

Hairless mice n = 60; 3 groups of 20 mice were irradiated with solar simulated ultraviolet radiation UVR throughout the study. Five single treatments with IngMeb were given at 4-week intervals Days 21, 49, 77, 105, and 133. Clobetasol propionate CP was applied once daily for 5 days prior to each IngMeb application, as well as 6 h and 1 day post treatment. One week after IngMeb treatment No. 1, 3, and 5 Days 28, 84, and 140, biopsies from four mice in each group were collected for histological evaluation of UV-damage on a standardized UV-damage scale 0–12. LSR 0–24 were assessed once daily Days 1–7 after each IngMeb treatment.

Results

IngMeb prevented progression of photodamage in terms of keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage with a lower composite UV-damage score on day 140 UVR 10.25 vs. UVR+IngMeb 6.00, p = 0.002 compared to UVR alone. IngMeb induced LSR, including erythema, flaking, crusting, bleeding, vesiculation, and ulceration. Concurrent CP increased LSR max LSR Tx 1–5: UVR+IngMeb+CP 3.6–5.5 vs. UVR+IngMeb 2.6–4.3 and provided better prevention of photodamage compared to IngMeb alone Day 140: UVR+IngMeb 6.00 vs. UVR+IngMeb+CP 3.00 p < 0.001.

Conclusion

Repeated field-directed treatments with IngMeb prevent progression of cutaneous photodamage in hairless mice, while CP cannot be used to alleviate IngMeb-induced LSR. The findings suggest that IngMeb may potentially serve as a prophylactic treatment for UV-induced tumors.



Autor: Andrés Már Erlendsson , Daniel Thaysen-Petersen, Christiane Bay, Andreas Hald, Kresten Skak, John Robert Zibert, Uwe Paasch, Ha

Fuente: http://plos.srce.hr/



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