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Open AccessArticle

Protective Effect of Pomegranate on Oxidative Stress and Inflammatory Response Induced by 5-Fluorouracil in Human Keratinocytes

1
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy
2
Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via Salvador Allende, 84081 Baronissi, SA, Italy
*
Author to whom correspondence should be addressed.
Antioxidants 2021, 10(2), 203; https://doi.org/10.3390/antiox10020203
Received: 29 December 2020 / Revised: 25 January 2021 / Accepted: 28 January 2021 / Published: 30 January 2021
5-Fluorouracil (5-FU) is a pyrimidine analogue used as an antineoplastic agent to treat multiple solid tumors. Despite its use and efficacy, it also has important side effects in healthy cells, including skin reactions, related to its pro-oxidant and pro-inflammatory potential. Although there are numerous remedies for chemotherapy-induced skin reactions, the efficacy of these treatments remains limited. In this study we focused on the effects of pomegranate (Punica granatum L.) juice extract (PPJE) on the oxidative and inflammatory state in 5-FU-treated human skin keratinocytes (HaCaT). The obtained results showed that PPJE significantly inhibited reactive oxygen species release and increased the cellular antioxidant response, as indicated by the increased expression of cytoprotective enzymes, such as heme oxygenase-1 and NAD(P)H dehydrogenase [quinone] 1. In these experimental conditions, PPJE also inhibited nitrotyrosine formation and 5-FU-induced inflammatory response, as indicated by the reduced cytokine level release. Moreover, PPJE inhibited nuclear translocation of p65-NF-κB, a key factor regulating the inflammatory response. In 5-FU-treated HaCaT cells PPJE also inhibited apoptosis and promoted wound repair. These results suggest a potential use of PPJE as an adjuvant in the treatment of the oxidative and inflammatory state that characterizes chemotherapy-induced skin side effects. View Full-Text
Keywords: 5-Fluorouracil; human keratinocytes; pomegranate juice extract; oxidative stress; inflammation; apoptosis; wound repair 5-Fluorouracil; human keratinocytes; pomegranate juice extract; oxidative stress; inflammation; apoptosis; wound repair
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MDPI and ACS Style

Rapa, S.F.; Magliocca, G.; Pepe, G.; Amodio, G.; Autore, G.; Campiglia, P.; Marzocco, S. Protective Effect of Pomegranate on Oxidative Stress and Inflammatory Response Induced by 5-Fluorouracil in Human Keratinocytes. Antioxidants 2021, 10, 203. https://doi.org/10.3390/antiox10020203

AMA Style

Rapa SF, Magliocca G, Pepe G, Amodio G, Autore G, Campiglia P, Marzocco S. Protective Effect of Pomegranate on Oxidative Stress and Inflammatory Response Induced by 5-Fluorouracil in Human Keratinocytes. Antioxidants. 2021; 10(2):203. https://doi.org/10.3390/antiox10020203

Chicago/Turabian Style

Rapa, Shara F.; Magliocca, Giorgia; Pepe, Giacomo; Amodio, Giuseppina; Autore, Giuseppina; Campiglia, Pietro; Marzocco, Stefania. 2021. "Protective Effect of Pomegranate on Oxidative Stress and Inflammatory Response Induced by 5-Fluorouracil in Human Keratinocytes" Antioxidants 10, no. 2: 203. https://doi.org/10.3390/antiox10020203

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