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

Abstract

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.

Protective Effects of Cannabidiol on Chemotherapy-Induced Oral Mucositis via the Nrf2/Keap1/ARE Signaling Pathways

“…Oxidative stress and proinflammatory cytokines are directly involved in mucosal injury secondary to tumor treatment and are key mediators of OM. Therefore, the control of oxidative stress and inflammatory response is essential to avoid harmful pathological reactions [ 34 ]. First, ROS production is the initiating factor in the pathological process of OM caused by radiotherapy and chemotherapy, leading to DNA damage and cell death.…”

Role for Plant-Derived Antioxidants in Attenuating Cancer Cachexia

“…However, the mechanisms underlying these benefits of PE on skeletal muscle remain to be determined and studies should investigate these effects at the cellular level to confirm potential therapeutic benefit. Lastly, PE has also been shown to alleviate oxidative stress and inflammation induced by the chemotherapeutic 5-Fluorouracil (5-FU) in human immortal keratinocyte cells, suggesting the potential for PE to protect against the off-target effects of 5-FU chemotherapy [ 142 ].…”

ER exit pathways and the control of proteostasis: Crucial role of the UPR, COPII, and ER-phagy in the secretory pathway

“…In contrast, UPR does not induce changes in the intracellular pattern of Sec16. Immunofluorescence was conducted on Huh7 cells as previously described (Amodio et al, 2017;Pagliara et al, 2020;Rapa et al, 2021). Briefly, Huh7 cells seeded on glass coverslips were either not treated (CTRL) or treated with 300 nM thapsigargin for 2 h and processed for immunofluorescence with anti-Sec31 (BD Transduction Laboratories) and anti-Sec16 (Bethyl Laboratories) specific antibodies.…”