Prostaglandins protect against murine hair injury produced by ionizing radiation or doxorubicin.
Several years ago we showed that prostaglandins (PGs) are potent radioprotective agents. To investigate further the potential use of these compounds we employed quantitative measures of murine hair loss and regrowth to assess the effects of PG administration before multi-dose fractionated radiation exposures. We compared these results with findings utilizing the thiol compounds WR-2721 or WR-1065, the "gold standard" laboratory radioprotectors. Three weeks after systemic administration of 16-16 dm PGE2 (Upjohn Company) or WR-2721, given 1 h before each dose of 2-4.5 Gy per fraction for 10-15 fractions, regrowing hair counts increased up to 100% compared to irradiated-only skin sites. The thiol compound effects were slightly superior to the PG effects in these studies. Local applications of 16-16 dm PGE2 or WR-1065 given 15 min before each radiation fraction also enhanced post-radiation hair regrowth, although systemic administration of either agent was more effective than the topical route. We also evaluated possible protective effects of PGs given before doxorubicin, measuring murine hair loss 1 week after parenteral injections of the drug. Five daily doses of doxorubicin, 0.1 mg/25 g animal, reduced the number of hairs in a 4.42 mm2 area of skin from 241 +/- 5 (controls) to 144 +/- 3. Misoprostol (G.D. Searle & Co.), 25 micrograms/mouse, applied locally 2 h before each dose of doxorubicin, resulted in 213 +/- 8 residual hairs. We conclude that clinical use of these compounds may provide significant protection of hair follicles and possibly other normal tissues (skin; oral, rectal, and bladder mucosa) lying within a radiation field or in patients treated with chemotherapeutic agents. Further assessment of possible tumor protection effects are needed, however.
Malkinson
F D
FD
Department of Dermatology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3833.
Geng
L
L
Hanson
W R
WR
D000284:Administration, Oral; D000287:Administration, Topical; D000505:Alopecia / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage; D004317:Doxorubicin / Q000494:pharmacology*; D006197:Hair / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects*; D007267:Injections; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016595:Misoprostol / Q000627:therapeutic use; D011453:Prostaglandins / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
D011453:Prostaglandins; D011837:Radiation-Protective Agents; D016595:Misoprostol; D004317:Doxorubicin; D015232:Dinoprostone