Topical isonicotinic acid hydrazide (isoniazid) as a new skin depigmenting compound

Topical isonicotinic acid hydrazide (isoniazid) as a new skin depigmenting compound Ahmadi Sara.1, Pourahmadi M.1, Aslani F.S.2, Kasraee B.3 1Jahrom University of Medical Sciences, Dept. of Dermatology, Jahrom, Iran, 2Shiraz University of Medical Sciences, Dept. of Pathology, Shiraz, Iran, 3Scientis Pharma, Research Department, Geneva, Switzerland

• INTRODUCTION & OBJECTIVES: Isonicotinic acid hydrazide (isoniazid) is the most commonly used antituberculosis medication. This molecule is a substrate for the enzyme peroxidase present within the tuberculosis bacillus and its metabolization by this enzyme is responsible for its bactericidal effect. In melanocytes, the enzyme peroxidase is involved in several steps of melanin synthesis and we have previously suggested that peroxidase substrates might act as skin depigmenting molecules. We report herein, for the first time, that isoniazid acts as a potent skin depigmenting molecule when used topically in black guinea pig model.

• MATERIAL & METHODS: Six uniformely black guinea pigs were treated with a cream containing 10% isoniazid on one of their ears and with the vehicle alone on their contralateral ears daily for two consecutive weeks. Histologic, Immunohistochemical and quantitative melanin measurement examinations were performed in biopsied sites from isoniazid-treated vs. vehicle treated areas.

• RESULTS: Visible depigmentation occured in isoniazid treated sites already after one week of application while the vehicle treated areas remained unchanged. Histologic (H&E and Fontana-Masson) and immunohistologic (Mela-A and HMB-45) examinations as well as spectrophotometric melanin quantification in the splitted epidermis unequivocally confirmed the significant depigmenting action of topical isoniazid.

• CONCLUSIONS: Isoniazid can serve as a novel lead compound for the discovery of new skin depigmenting molecules in the future. Peroxidase substrates may be considered as a new family of skin depigmenting agents.

Source of Information: Poster 505. 2012 (06) – 9th Spring Symposium of the EADV (European Academy of Dermatology and Venerology) – Verona, Italiy (Italia)