Topical or Systemic 16,16 Dm Prostaglandin E₂or WR-2721 (WR-1065) Protects Mice from Alopecia after Fractionated Irradiation

Abstract

Our previous studies in mice demonstrated that systemic or topical 16,16 dm PGE2 protected against single dose radiation-induced hair loss. We have now investigated prostaglandin, or WR-2721, protection against murine alopecia produced by varying doses and schedules of fractionated radiation. On days one to eight after hair was plucked from the thighs of B6D2F1 mice, groups of 6 animals each were given daily exposures of 4.0 or 4.5 Gy for 5 days; 2.5, 3.5, 4.5 or 5.5 Gy for 10 days; or 2 Gy for 15 days. One hour before irradiation each mouse received 10 microgram 16,16 dm PGE2, either by subcutaneous injection into the neck or topical application, 8 mg WR-2721 by injection, or 0.3 mg WR-1065 by topical application. Three weeks later counts of regrowing hairs were recorded from excised skin samples. For the radioprotectors used, hair regrowth was increased 25-100% in the various radiation groups in comparison to irradiated-only control sites. In some studies with the radioprotector given systemically, WR-2721 afforded slightly greater radioprotection than 16,16 dm PGE2. The two compounds were essentially equally radioprotective in the topical application studies. Since both systemic and topical applications of the agents tested enhanced hair regrowth following radiation, we conclude that clinical use of these compounds may provide some protection of hair follicles, and perhaps other tissues, lying within a radiation therapy field.

Radiation dermatitis: Clinical presentation, pathophysiology, and treatment 2006

“…In animal models, both have been used to protect hair follicles and other skin structures. 42,43 Celecoxib, a COX-2 inhibitor, has been shown to reduce skin damage after radiation in mice, exhibiting selective reduction of chemokine and receptor messenger RNA expression in irradiated skin but not in irradiated tumor. 44 TGF-b, a peptide which has a fundamental role in controlling proliferation of many cell types, is intricately involved in the development of chronic radiation dermatitis.…”

The preventive effect of vitamin D3 on radiation-induced hair toxicity in a rat model

“…In some studies related with radioprotectors, systemic and topical applications of WR-2721 and PGE 2 enhanced hair regrowth following irradiation and provided some protection of hair follicles, and probably other tissues, lying under a radiation therapy field (Geng et al, 1992). In a study, water fraction of ginseng administration exerted a potent effect on the recovery of the hair follicles by its combined effects on proliferation and apoptosis of the cells in the hair follicle (Kim et al, 1998).…”

Radioprotective effect of misoprostol on mouse spermatogonial stem cells

“…In addition, previous results indicated that spermatogonial stem cells also become less sensitive towards the induction of reciprocal translocations by higher doses of X-irradiation (Sankaranarayanan et al, 1995). So far only prostaglandin-mediated protection responses of in i o cell renewal systems as a whole, such as bone marrow (Hanson & Ainsworth, 1985 ;Walden et al, 1987), hair follicles (Geng et al, 1992), intestine (Hanson & Thomas, 1983) or germinal epithelium, have been described. In the present study we have further dissected this response and show for the first time that the protective effect is clearly present in the stem cell compartment -and, moreover, for both proliferating and quiescent stem cells.…”

“…Furthermore, it was demonstrated that various prostaglandins, or synthetic analogues such as misoprostol, protected the mucosa of the digestive tract from injury by non-steroidal anti-inflammatory agents, heat, acids and bases (Robert et al, 1979) or X-irradiation (Hanson & Thomas, 1983). Also other cell renewal systems such as bone marrow (Hanson & Ainsworth, 1985 ;Walden et al, 1987) and hair follicles (Geng et al, 1992) have been found to become more radioresistant by prostaglandin treatment. The mechanism for the radioprotective effect is unknown.…”