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In a new strategy, we sought to determine whether topically applied vasoconstrictor, with its accompanying transient skin hypoxia and exclusion of systemic drug, would prevent or suppress radiotherapy or chemotherapy-induced alopecia. Topical vasoconstrictor was applied to 1-cm2 skin patches on the backs of 10-day-old rats and minutes later they received either 7.1 gray (Gy) whole-body radiation or systemic N-nitroso-N-methylurea (MNU) or Cytoxan. The degree of alopecia was scored 10 days later by visual assessment (% coat retention) and hair follicle histologic analysis. Topical application of epinephrine or norepinephrine in an alcohol:water delivery vehicle induced clear skin blanch, and in a dose-dependent manner, topical epinephrine or norepinephrine (20–1,000 mM) applied before 7.1 Gy irradiation conferred 95% of coat retention in the treated skin patches versus 0% coat retention in vehicle controls, or in skin outside the treated patches. By histology, small numbers of dystrophic hair follicles were observed in hairless skin versus the normal density of anagen follicles in the immediately adjacent, drug-protected skin patches at day 20; protected coats were retained into adulthood. Topical epinephrine or norepinephrine before systemic MNU (30 ug/gm body weight) conferred up to 95% of coat retention in treated skin patches versus 0% coat retention elsewhere. Epinephrine-conferred % coat retention dropped to 16% in rats that received systemic Cytoxan, a drug whose plasma half-life is at least 8- to 10-fold longer than MNU. A general strategy is discussed for the use of topical epinephrine or norepinephrine in the clinic to provide an inexpensive and convenient strategy to prevent cancer therapy-induced alopecia.Nearly two-thirds of cancer patients who receive chemotherapy experience chemotherapy-induced hair loss, or alopecia. To improve clinical management of alopecia, the present study explored a new strategy, based on topical application of a vasoconstrictor prior to radiation or chemotherapy. In a rat alopecia model, application of epinephrine or norepinephrine before radiation or chemotherapy was found to confer up to 95% coat retention. Topical application of the vasoconstrictors induced a visible skin blanch in neonate rats, with protected coat growth occurring at the blanched sites. The results support further development of a topical vasoconstrictor strategy for clinical use.