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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

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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.

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Abbreviations

BaP:

Benzo[a]pyrene

HE/HP-β-CyD:

2-Hydroxypropyl-β-cyclodextrin

AhR:

Aryl hydrocarbon receptor

PAHs:

Polycyclic aromatic hydrocarbons

ROS:

Reactive oxygen species

HE:

Hesperetin

DCFDA 2:

7-Dichlorofluorescein diacetate

GAPDH:

Glyceraldehyde-3-phosphatase dehydrogenase

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Authors and Affiliations

  1. “Foundation Prof. Antonio Imbesi”, Pharmaco-Biological Department, School of Pharmacy, University of Messina, Vill. SS. Annunziata, 98168, Messina, Italy

    Antonietta Melchini

  2. Interdepartmental Centre of Experimental, Environmental and Occupational Toxicology (CITSAL), University of Messina, 98125, Messina, Italy

    Stefania Catania & Chiara Costa

  3. Pharmaco-Chemical Department School of Pharmacy, University of Messina, Vill. SS. Annunziata, 98168, Messina, Italy

    Rossana Stancanelli & Silvana Tommasini

  4. Department of Occupational Medicine, School of Medicine, University of Messina, 98125, Messina, Italy

    Chiara Costa

  5. Interdepartmental Centre of Experimental, Environmental and Occupational Toxicology (CITSAL), Azienda Ospedaliera Universitaria “G. Martino”, pad. H, Via Consolare Valeria, 1, 98125, Messina, Italy

    Antonietta Melchini

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  1. Antonietta Melchini
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  2. Stefania Catania
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  4. Silvana Tommasini
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Correspondence to Antonietta Melchini.

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Melchini, A., Catania, S., Stancanelli, R. et al. 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. Cell Biol Toxicol 27, 371–379 (2011). https://doi.org/10.1007/s10565-011-9194-6

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