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Topical application of 17β‐estradiol ( E 2 ) improves skin flap survival through activation of endothelial nitric oxide synthase in rats
Author(s) -
Shafighi Maziar,
Fathi Ali R.,
Brun Claudio,
Huemer Georg M.,
Wirth Raphael,
Hunger Robert,
Banic Andrej,
Constantinescu Mihai A.
Publication year - 2012
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2012.00816.x
Subject(s) - enos , nitric oxide , in vivo , umbilical vein , nitric oxide synthase , in vitro , placebo , andrology , endothelial stem cell , medicine , wound healing , chemistry , endocrinology , immunology , biology , pathology , biochemistry , alternative medicine , microbiology and biotechnology
This study investigates the influence of 17β‐estradiol ( E 2 ) on nitric oxide ( NO ) production in endothelial cell cultures and the effect of topical E 2 on the survival of skin flap transplants in a rat model. Human umbilical vein endothelial cells were treated with three different E 2 concentrations and nitrite ( NO 2 ) concentrations, as well as endothelial nitric oxide synthase ( eNOS ) protein expressions were analyzed. In vivo, random‐pattern skin flaps were raised in female W istar rats 14 days following ovariectomy and treated with placebo ointment (group 1), E 2 as gel (group 2), and E 2 via plaster (group 3). Flap perfusion, survival, and NO 2 levels were measured on postoperative day 7. In vitro, E 2 treatment increased NO 2 concentration in cell supernatant and eNOS expression in cell lysates ( p < 0.05). In vivo, E 2 treated (gel and plaster groups) demonstrated significantly increased skin flap survival compared to the placebo group ( p < 0.05). E 2 plaster‐treated animals exhibited higher NO 2 blood levels than placebo ( p < 0.05) paralleling the in vitro observations. E 2 increases NO production in endothelial cells via eNOS activation. Topical E 2 application can significantly increase survival of ischemically challenged skin flaps in a rat model and may augment wound healing in other ischemic situations via activation of NO production.