Olopatadine hydrochloride accelerates the recovery of skin barrier function in mice.
BACKGROUND
The skin barrier function in patients with atopic dermatitis is disrupted and prolonged topical steroid therapy produces epidermal barrier disturbance. Olopatadine hydrochloride (olopatadine; Allelock; Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan) is an antiallergic drug with histamine H(1) receptor antagonistic action. This drug alleviates skin inflammation and decreases the number of scratching episodes in a murine model of chronic contact dermatitis.


OBJECTIVE
To investigate the effects of olopatadine and a steroid on the recovery of skin barrier function after barrier disruption in mice.


METHODS
The skin barrier of the ears of mice was disrupted by tape stripping. The recovery of skin barrier function was monitored by measurement of transepidermal water loss (TEWL) after barrier disruption. Epidermal hyperplasia was induced by repeated tape stripping for 7 days. Olopatadine was administered orally once daily from 3 days before the first barrier disruption. Betamethasone 17-valerate (betamethasone) was applied topically once daily from 3 days before barrier disruption.


RESULTS
Tape stripping led to a significant increase in TEWL. TEWL decreased with time after tape stripping and the skin barrier function recovered by over 60% within 9 h after tape stripping. The recovery of skin barrier in olopatadine-treated mice was significantly accelerated, compared with that in vehicle-treated mice. In contrast, the skin barrier recovery in mice treated with topical betamethasone was significantly delayed, compared with that in vehicle-treated mice. Combined treatment with olopatadine and betamethasone ameliorated the delay in barrier recovery induced by topical treatment with betamethasone. In addition, olopatadine significantly prevented the increase in epidermal thickness induced by prolonged barrier disruption.


CONCLUSIONS
These results suggest that systemic administration of olopatadine accelerates the recovery of skin barrier function and ameliorates the adverse effects of topical steroids on skin barrier recovery.
Amano
T
T
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co Ltd, 1188 Shimotogari, Sunto-Gun, Shizuoka, Japan. toru.amano@kyowa.co.jp
Takeda
T
T
Yano
H
H
Tamura
T
T
D000818:Animals; D001623:Betamethasone / Q000009:adverse effects; D003990:Dibenzoxepins / Q000494:pharmacology*; D004817:Epidermis / Q000473:pathology; D005938:Glucocorticoids / Q000009:adverse effects; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000069605:Olopatadine Hydrochloride; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D014870:Water Loss, Insensible / Q000187:drug effects*
D003990:Dibenzoxepins; D005938:Glucocorticoids; D039563:Histamine H1 Antagonists, Non-Sedating; D000069605:Olopatadine Hydrochloride; D001623:Betamethasone