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 (GAG) markedly increases melanin production within 24 h. To determine whether OAG can increase melanin production in vivo, increasing concentrations of OAG (10-50 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 GAG-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 GAG, dipalmitoylglycerol (diC(16)), dioctanoylglycerol (diC(8)), each 50 mg/ml, 20 mu l/application, and propylene glycol vehicle alone for 5 d. Increased pigmentation was visible after 10 d in the OAG and diC(8) sites but not in diC(16) 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/cm(2), 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 clinicallyand histologically closely resembles ultraviolet-induced tanning.