phenylthiourea and Vitiligo

Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.

Topics: Agaricales; Apoptosis; Butanols; Caspase 3; Catalytic Domain; Cell Survival; Cells, Cultured; Chelating Agents; Copper; Endoplasmic Reticulum Stress; Enhancer Elements, Genetic; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation; Humans; Hypopigmentation; Inhibitory Concentration 50; Interleukin-8; Melanocytes; Monophenol Monooxygenase; Phenylthiourea; Pigmentation; Reactive Oxygen Species; RNA, Small Interfering; Skin Lightening Preparations; Up-Regulation; Vitiligo

The incidence of vitiligo varies from country to country. In the present study, seventy cases of vitiligo have been studied from skin out patient department of the Institute of Post-graduate Medicine & Research over a period of 2 years. The prevalence rate of vitiligo among the total out patient attendent was 0.4 per cent. 85 per cent of the cases belonged to the age group to 11-40 years. Male and female ratio was 2:1. Precipitating factors like physical injury, mental stress and strain had close link with development of skin lesion. In 11.4 per cent cases near relations were involved. Skin lesions according to the site showed lower extremity to be the maximally involved area and the genital areas were least involved.

Topics: Adolescent; Adult; Bangladesh; Child; Child, Preschool; Dermatologic Agents; Drug Evaluation; Female; Humans; Infant; Infant, Newborn; Male; Phenylthiourea; Photochemotherapy; Vitiligo