Cell Biology and Toxicology

, Volume 27, Issue 5, pp 371–379 | Cite as

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

  • Antonietta Melchini
  • Stefania Catania
  • Rossana Stancanelli
  • Silvana Tommasini
  • Chiara Costa


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.


Aryl hydrocarbon receptor Benzo[a]pyrene Hesperetin Cytochrome P450 1A1 Ex vivo Human skin Oxidative stress 







Aryl hydrocarbon receptor


Polycyclic aromatic hydrocarbons


Reactive oxygen species




7-Dichlorofluorescein diacetate


Glyceraldehyde-3-phosphatase dehydrogenase


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Antonietta Melchini
    • 1
    • 5
  • Stefania Catania
    • 2
  • Rossana Stancanelli
    • 3
  • Silvana Tommasini
    • 3
  • Chiara Costa
    • 2
    • 4
  1. 1.“Foundation Prof. Antonio Imbesi”, Pharmaco-Biological Department, School of PharmacyUniversity of MessinaMessinaItaly
  2. 2.Interdepartmental Centre of Experimental, Environmental and Occupational Toxicology (CITSAL)University of MessinaMessinaItaly
  3. 3.Pharmaco-Chemical Department School of PharmacyUniversity of MessinaMessinaItaly
  4. 4.Department of Occupational Medicine, School of MedicineUniversity of MessinaMessinaItaly
  5. 5.Interdepartmental Centre of Experimental, Environmental and Occupational Toxicology (CITSAL)Azienda Ospedaliera Universitaria “G. Martino”, pad. HMessinaItaly

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