Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds.
Although many hypo-pigmenting agents are currently available, the demand for novel whitening agents is increasing, in part due to the weak effectiveness and unwanted side effects of currently available compounds. To screen for novel hypo-pigmenting agents, many methodologies such as cell culture and enzymatic assays are routinely used. However, these models have disadvantages in terms of physiological and economic relevance. In this study, we validated zebrafish as a whole-animal model for phenotype-based screening of melanogenic inhibitors or stimulators. We used both the well-known melanogenic inhibitors (1-phenyl-2-thiourea, arbutin, kojic acid, 2-mercaptobenzothiazole) and newly developed small molecule compounds (haginin, YT16i). All the tested compounds produced inhibitory effects on the pigmentation of zebrafish, most likely due to their inhibitory potential on tyrosinase activity. In simultaneous in vivo toxicity tests, a newly developed melanogenic inhibitor YT16i showed massive abnormalities in terms of deformed morphologies and cardiac function. Together, these results provide a rationale in screening and evaluating the putative melanogenic regulatory compounds. We suggest that the zebrafish system is a novel alternative to mammalian models, with several advantages including the rapidity, cost-effectiveness, and physiological relevance.
Choi
Tae-Young
TY
Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, South Korea.
Kim
Jin-Hwa
JH
Ko
Dong Han
DH
Kim
Cheol-Hee
CH
Hwang
Jae-Sung
JS
Ahn
Soomi
S
Kim
Sun Yeou
SY
Kim
Chang-Deok
CD
Lee
Jeung-Hoon
JH
Yoon
Tae-Jin
TJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001104:Arbutin / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004625:Embryo, Nonmammalian; D008543:Melanins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D023421:Models, Animal; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010641:Phenotype; D010858:Pigmentation; D011753:Pyrones / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000502:physiology
D000975:Antioxidants; D001562:Benzimidazoles; D008543:Melanins; D011753:Pyrones; C030698:2-mercaptobenzimidazole; C011890:kojic acid; D001104:Arbutin; D014442:Monophenol Monooxygenase