title: Inhibition of UVB-induced skin phototoxicity by a grape seed extract as modulator of nitrosative stress, ERK/NF-kB signaling pathway and apoptosis, in SKH-1 mice.
abstract: Molecular mechanisms concerning the modulation of nitrosative stress, signal transduction and proliferation/apoptosis by a grape seed extract, Burgund Mare variety (BM), in SKH-1 mice exposed to UVB, were investigated. The animals were irradiated with single and multiple doses of UVB in 10 consecutive days. In each experiment were used five groups of animals: control, vehicle, UVB irradiated, vehicle+UVB, BM+UVB. The extract was applied topically, 30 min before each UVB exposure, in a dose of 4 mg total polyphenols/cm(2). BM remarkably inhibited UVB-induced activation of inducible nitric oxide synthase (iNOS) and therefore generation of nitric oxide (NO) and nitrotyrosine, in a UVB single dose regimen. BM also suppressed NF-kB activation by UVB but did not affect the activity of total ERK 1/2. In multiple UVB irradiations, BM increased NO formation and total ERK 1/2 activity and reduced iNOS activity and nitrotyrosine levels, inhibited cell proliferation, diminished p53 and caspase-3 immunoreactivities and increased the percentage of Bcl-2 positive cells. We concluded that BM modulates the apoptotic response of SKH-1 mice skin in UVB irradiation by the inhibition of p53, caspase-3, Bax/Bcl-2 and proliferating cell nuclear antigen expressions, as well as by reducing the activation of iNOS and NF-kB.
authors.affiliation: Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, 1-3 Clinicilor Str., 400012 Cluj-Napoca, Romania. adrianafilip33@yahoo.com
authors.forename: Gabriela Adriana
authors.initials: GA
authors.lastname: Filip
authors.forename: Ion Dan
authors.initials: ID
authors.lastname: Postescu
authors.forename: Pompei
authors.initials: P
authors.lastname: Bolfa
authors.forename: Cornel
authors.initials: C
authors.lastname: Catoi
authors.forename: Adriana
authors.initials: A
authors.lastname: Muresan
authors.forename: Simona
authors.initials: S
authors.lastname: Clichici
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D056604:Grape Seed Extract / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008812:Mice, Hairless; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D012871:Skin Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D056604:Grape Seed Extract; D016328:NF-kappa B; D011837:Radiation-Protective Agents; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D053148:Caspase 3