Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro, In Vivo and Clinical Studies

Abstract

Chemoradiation-induced mucositis is a debilitating condition of the gastrointestinal tract eventuating from antineoplastic treatment. It is believed to occur primarily due to oxidative stress mechanisms, which generate Reactive Oxygen Species (ROS). The aim of this scoping review was to assess the role of oxidative stress in the development of Oral Mucositis (OM). Studies from the literature, published in MEDLINE and SCOPUS, that evaluated the oxidative stress pathways or antioxidant interventions for OM, were retrieved to elucidate the current understanding of their relationship. Studies failing inclusion criteria were excluded, and those suitable underwent data extraction, using a predefined data extraction table. Eighty-nine articles fulfilled criteria, and these were sub-stratified into models of study (in vitro, in vivo, or clinical) for evaluation. Thirty-five clinical studies evaluated antioxidant interventions on OM’s severity, duration, and pain, amongst other attributes. A number of clinical studies sought to elucidate the protective or therapeutic effects of compounds that had been pre-determined to have antioxidant properties, without directly assessing oxidative stress parameters (these were deemed “indirect evidence”). Forty-seven in vivo studies assessed the capacity of various compounds to prevent OM. Findings were mostly consistent, reporting reduced OM severity associated with a reduction in ROS, malondialdehyde (MDA), myeloperoxidase (MPO), but higher glutathione (GSH) and superoxide dismutase (SOD) activity or expression. Twenty-one in vitro studies assessed potential OM therapeutic interventions. The majority demonstrated successful a reduction in ROS, and in select studies, secondary molecules were assessed to identify the mechanism. In summary, this review highlighted numerous oxidative stress pathways involved in OM pathogenesis, which may inform the development of novel therapeutic targets.

Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models

“…Rtibi et al, found that the antioxidant biomarkers SOD, CAT, and GPx decreased in 5-FU and CAP-induced intestinal mucositis in a rat model, confirming the role of oxidative stress in the onset of intestinal mucositis [ 195 ]. Consistently, the use of antioxidants has been found to reduce the severity of mucosal injury in vitro, in vivo, and in clinical studies [ 261 ].…”

New Perspectives on the Sustainable Employment of Chestnut Shells as Active Ingredient against Oral Mucositis: A First Screening

“…Oxidative stress is the main factor in the basis development of OM, which induces to the activation of the apoptotic process, leading to the clinical manifestation of mucosal damage. Pro-inflammatory cytokines are in a positive feedback mechanism, conducting to ulceration, which compromises the mucosal integrity, allowing several microorganisms to penetrate tissues and increasing the sepsis risk [ 2 , 43 ]. The five phenolic compounds mentioned above were found at higher concentrations in all the extracts.…”

“…Oral mucositis (OM) is one of the most common side effects of antineoplastic treatments, namely chemo- and/or radiotherapy, and is defined as an acute inflammatory, ulcerative, and painful disorder that severely degrades the quality of life of patients [ 1 , 2 , 3 ]. Ulceration of buccal mucosa compromises the natural defensive barrier, allowing oral bacteria and inflammatory cytokines to enter underlying tissues and the systemic blood supply [ 2 ]. During the antineoplastic treatments, reactive oxygen species (ROS) are generated, leading to the development of oxidative stress, one of the principal phenomena in the basis of OM development [ 2 , 3 ].…”

“…Ulceration of buccal mucosa compromises the natural defensive barrier, allowing oral bacteria and inflammatory cytokines to enter underlying tissues and the systemic blood supply [ 2 ]. During the antineoplastic treatments, reactive oxygen species (ROS) are generated, leading to the development of oxidative stress, one of the principal phenomena in the basis of OM development [ 2 , 3 ]. An imbalance between the body’s synthesis of oxidants and antioxidant defenses of human body is known as oxidative stress, which may result in a wide range of diseases, including diabetes, cardiovascular or neurodegenerative diseases, and, at the last step, cancer [ 4 , 5 ].…”

Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment

“…In another in vitro study, Yoshida et al demonstrate that TJ-41 attenuates 5-fluorouracil-induced apoptosis, by inhibiting the production of mitochondrial reactive oxygen species [66]. This leads to the suggestion that TJ-41 could be used to treat oral mucositis in patients receiving chemotherapy [71]. A clinical study confirms that TJ-84 improves mucositis in esophageal cancer patients treated with chemotherapy [61].…”