Topically applied diacylglycerols increase pigmentation in guinea pig skin.
Exposure of human and murine melanocytes in vitro to the diacylglycerol (DAG) 1-oleoyl-2-acetyl-sn-glycerol (OAG) markedly increases melanin production within 24 h. To determine whether OAG can increase melanin production in vivo, increasing concentrations of OAG (10-60 mg/ml) in propylene glycol were applied daily for 5 d to shaved guinea pigs. Dose-dependent increased pigmentation was visible first on days 17-22 and persisted for 10-14 weeks. Peak epidermal melanin content in OAG-treated sites was more than twice that of untreated or vehicle-treated sites, as assessed by computerized image analysis of Fontana-Masson stained biopsy cross sections. In another experiment to assess the mechanism of DAG-mediated pigmentation, guinea pigs received twice daily separate applications of OAG, dipalmitoylglycerol (diC16), dioctanoylglycerol (diC8), each 50 mg/ml, 20 microliters/application, and propylene glycol vehicle alone for 5 d. Increased pigmentation was visible after 10 d in the OAG and diC8 sites but not in diC16 or vehicle sites. These results correlate with the reported ability of these compounds to activate protein kinase C in vitro. In a final experiment, guinea pigs received OAG 25 mg/ml three times daily to one test site, and once daily ultraviolet B (70 mJ/cm2, equivalent to 0.6 minimal erythemal dose) radiation to another for 10 d. The OAG and ultraviolet B test sites developed comparable pigmentation by both clinical and histologic criteria. Our data demonstrate that topically applied DAGs can produce a long-lasting increase in epidermal pigmentation, presumably through protein kinase C activation, which clinically and histologically closely resembles ultraviolet-induced tanning.
Allan
A E
AE
Department of Dermatology, Boston University School of Medicine, Massachusetts 02118, USA.
Archambault
M
M
Messana
E
E
Gilchrest
B A
BA
D000287:Administration, Topical; D000818:Animals; D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000378:metabolism; D012867:Skin / Q000033:anatomy & histology / Q000187:drug effects; D012880:Skin Pigmentation / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays
D004075:Diglycerides; D008543:Melanins; C038237:1-oleoyl-2-acetylglycerol