Abstract
Intestinal epithelial cells (IECs) play a pivotal role in maintaining intestinal homeostasis. Different noxious agents, among them also anticancer therapies, can impair intestinal epithelial integrity triggering inflammation and oxidative stress. A frequent complication of chemotherapy is gastrointestinal mucositis, strongly influencing the effectiveness of therapy, increasing healthcare costs, and impairing patients’ quality of life. Different strategies are used to treat gastrointestinal mucositis, including products from natural sources. Our study focused on the effect of pomegranate (Punica granatum L.) juice extract on IEC-6 cells, both during inflammatory conditions and following treatment with 5-fluorouracil (5-FU). The polyphenolic profile of pomegranate juice was characterized in detail by Online Comprehensive two dimensional Liquid Chromatography-Mass Spectrometry. The evaluation of pomegranate juice extract in IEC-6 indicates a significant inhibition in proinflammatory factors, such as cytokines release, cyclooxygenase-2 and inducible nitric oxide synthase expression, and nitrotyrosine formation. Pomegranate also inhibited oxidative stress and adhesion protein expression. In 5-FU-treated IEC-6, pomegranate also inhibited both inflammatory and oxidative stress parameters and apoptosis. It promoted wound repair and tight junction expression. These results suggest a potential use of pomegranate as an adjuvant in the treatment of intestinal inflammatory and oxidative stress states, which also occur during chemotherapy-induced mucositis.
Highlights
The gut is a complex organ playing a key role in nutrients absorption and tolerance for harmless/beneficial microorganisms, while maintaining the ability to defend itself from pathogenic microorganisms [1]
Considering the properties of polyphenols present in pomegranate juice extract (PPJE), in this study we evaluated its effect on inflammatory and oxidative stress mediators in intestinal epithelial cells (IECs) both during inflammatory response and 5-Fluorouracil (5-FU) treatment
We evaluated the ability of PPJE to influence nitrotyrosine formation, a product of tyrosine nitration mediated by reactive nitrogen species, such as peroxynitrite anion and nitrogen dioxide
Summary
The gut is a complex organ playing a key role in nutrients absorption and tolerance for harmless/beneficial microorganisms, while maintaining the ability to defend itself from pathogenic microorganisms [1]. Intestinal epithelial cells (IECs) can perceive and respond to microbial or external stimuli to strengthen barrier function and participate in an adequate immune response [3] associated with an imbalance in the body’s redox defense systems, giving rise to oxidative stress, which is presently considered as potentially critical in the pathogenesis, progression, and severity of IBDs [4]. Both inflammation and oxidative stress are linked as side effects at the gastrointestinal level (mucositis) of chemotherapy (CT) and radiotherapy (RT). The specific mechanism of mucositis, along with its clinical presentation, depends on the anatomical site involved (oral or gastrointestinal) and on the type of CT and RT [8,9]
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