Possible Role of NRF2 in Cell Response to OZOILE (Stable Ozonides) in Children Affected by Lichen Sclerosus of Foreskin

Author:

Saija Caterina1ORCID,Currò Monica1ORCID,Arena Salvatore2,Bertuccio Maria Paola1ORCID,Cassaro Fabiola2ORCID,Montalto Angela Simona2,Colonna Michele Rosario2,Caccamo Daniela1ORCID,Romeo Carmelo2ORCID,Impellizzeri Pietro2ORCID

Affiliation:

1. Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, 98124 Messina, Italy

2. Department of Human Pathology of Adult and Childhood “G. Barresi”, University of Messina, 98124 Messina, Italy

Abstract

Lichen sclerosus (LS) is a chronic inflammatory disease of the skin, and the gold standard for treatment is the use of the very potent topical steroids, but they can have side effects. Previously, we demonstrated that OZOILE (stable ozonides) were effective in children affected by LS, reducing the inflammatory process and stimulating tissue regeneration of the foreskin, showing a similar efficacy to steroid treatment. In this study, the modulation of inflammatory and oxidative stress pathways was evaluated by qRT-PCR and Western blotting in foreskins affected by LS removed from patients untreated or treated with OZOILE or corticosteroid cream formulations for 7 days before circumcision. OZOILE induced a significant increase in NRF2 and SOD2 levels, while it did not produce change in MIF, NF-kB subunits, and MMPs in comparison to untreated foreskins. Conversely, steroid topical treatment produced a significant reduction in the expression of p65, MIF, and MMP9, but it did not cause variation in NRF2 and SOD2 levels. These results demonstrate that the use of OZOILE as cream formulation exhibits effects on NRF2 signaling, and it does not induce NF-κB activation, unlike corticosteroids. On the basis of our biochemical data, further studies evaluating the role of NRF2 signaling cascade are necessary.

Publisher

MDPI AG

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