Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5852122 | Food and Chemical Toxicology | 2013 | 11 Pages |
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/cm2. 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.
Keywords
MnSODDPPHABTSUVBNF-kBBcl-2ERKRNSAP-1iNOSdiaminobenzidine tetrahydrochlorideGSPIKKαultraviolet radiation BCPDsAPAFPCNATNFPBSp53DABSDSDNAMAPKONOO−ROSProliferating Cell Nuclear Antigenapoptotic protease activating factor-1Nitrosative stressdeoxyribonucleic acidinterleukinBaxELISAEnzyme-linked immunosorbent assayCell proliferationApoptosisGrape seedCyclobutane pyrimidine dimerssodium dodecylsulfateinducible nitric oxide synthasemanganese superoxide dismutasetumor necrosis factorNuclear factor-kBPhosphate buffered salineB-cell lymphoma 2Nitric oxideSignal transductionBcl-2-associated X proteinTumor suppressor proteinactivator protein 1mitogen-activated protein kinasePeroxynitritehigh performance liquid chromatographyHPLCTotal polyphenolsreactive nitrogen speciesReactive oxygen species
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Authors
Gabriela Adriana Filip, Ion Dan Postescu, Pompei Bolfa, Cornel Catoi, Adriana Muresan, Simona Clichici,