title: Interaction of a functionalized complex of the flavonoid hesperetin with the AhR pathway and CYP1A1 expression: involvement in its protective effects against benzo[a]pyrene-induced oxidative stress in human skin.
abstract: Skin cancer pathogenesis is partially associated to the oxidative stress conditions induced by environmentally carcinogens such as benzo[a]pyrene (BaP). The protective effects against BaP-induced oxidative stress of the flavonoid hesperetin as a complex with the 2-hydroxypropyl-β-cyclodextrin (HE/HP-β-CyD) have been evaluated using an ex vivo human skin model. Human healthy skin has been pre-treated with the functionalized complex HE/HP-β-CyD (0.5-50 μM) before BaP (5 μM) application simulating occupational and environmental exposure. Oxidative stress was evaluated in terms of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheyltetrazolium bromide reduction, protein peroxidation and reactive oxygen species (ROS) formation. Additionally, it has been investigated whether the potential protective effects of HE/HP-β-CyD may be correlated to the interaction with aryl hydrocarbon receptor (AhR) pathway. A significant protection by HE/HP-β-CyD against the BaP-induced increase in ROS and carbonyl compound production, as well as reduction in tissue viability, has been observed (p<0.001). Results obtained showed that HE/HP-β-CyD was also able to reduce BaP-induced AhR and CYP1A1 protein expression (p<0.001). Experimental evidences provided from this study suggest significant preventive properties of HE/HP-β-CyD in the toxicity caused by environmental carcinogens such as PAHs.
authors: Foundation Prof. Antonio Imbesi, Pharmaco-Biological Department, School of Pharmacy, University of Messina, Vill. SS. Annunziata, 98168 Messina, Italy. amelchini@pharma.unime.it
authors: Antonietta
authors: A
authors: Melchini
authors: Stefania
authors: S
authors: Catania
authors: Rossana
authors: R
authors: Stancanelli
authors: Silvana
authors: S
authors: Tommasini
authors: Chiara
authors: C
authors: Costa
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001564:Benzo(a)pyrene; D016923:Cell Death / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D020011:Protective Agents; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001564:Benzo(a)pyrene; D006569:Hesperidin; D019363:Cytochrome P-450 CYP1A1; C013015:hesperetin