Proton pump inhibitors as a possible cause of vitiligo: an in vivo and in vitro study.
BACKGROUND
Vitiligo is an acquired depigmentation disorder of melanocytes. Recently, some clinical reports have suggested that proton pump inhibitors (PPIs) may worsen vitiligo, but their effects on melanocytes have yet to be elucidated.


OBJECTIVE
We investigated the effect of PPIs on melanogenesis in vivo and in vitro.


METHODS
We examined the effect of PPIs on melanogenesis in B16 murine melanoma cells by measuring melanin content and tyrosinase (TYR) activity. TYR and tyrosinase-related protein-1 (TRP-1) were monitored by western blotting. Finally, a PPI was applied to zebrafish embryos to investigate its in vivo effect on pigmentation.


RESULTS
In agreement with our clinical experience of worsened vitiligo after PPI treatment, PPIs decreased both melanin content and TYR activity. Western blotting showed that PPIs decreased TYR and TRP-1 protein levels. In the zebrafish test, PPIs inhibited body pigmentation in a dose-dependent manner.


CONCLUSIONS
These results suggest that the functional inhibition of melanization by PPIs may induce or aggravate vitiligo lesions in genetically predisposed patients.
Department of Dermatology, School of Medicine and Research Institute of Medical Sciences, Chungnam National University, Daejeon, Korea.
J M
JM
Shin
J Y
JY
Lee
D Y
DY
Lee
T Y
TY
Yoon
J C
JC
Lee
E H
EH
Lim
K C
KC
Sohn
Y H
YH
Lee
M
M
Im
Y J
YJ
Seo
C D
CD
Kim
J H
JH
Lee
Y
Y
Lee
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000188:drug therapy*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000378:metabolism; D057045:Laryngopharyngeal Reflux / Q000188:drug therapy*; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D023421:Models, Animal; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010858:Pigmentation; D011257:Pregnancy Proteins / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D014820:Vitiligo / Q000175:diagnosis* / Q000209:etiology*; D015027:Zebrafish
D007370:Interferon Type I; D008543:Melanins; D011257:Pregnancy Proteins; D054328:Proton Pump Inhibitors; C020947:interferon tau; D014442:Monophenol Monooxygenase