Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease

Bourgonje, Arno R.; Feelisch, Martin; Faber, Klaas Nico; Pasch, Andreas; Dijkstra, Gerard; Goor, Harry van

doi:10.1016/j.molmed.2020.06.006

Cited by 196 publications

(153 citation statements)

References 92 publications

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“…A recent study has concluded that low molecular mass systemic thiols might play a role in the inflammatory and oxidative stress pathways involved in both chronic obstructive pulmonary disease (COPD) and cardiovascular disease [ 91 ]. The levels of systemic free thiols can be influenced by nutritional or therapeutic intervention [ 92 ]. For these reasons, many clinical trials have evaluated the efficacy of N -acetylcysteine (NAC) administration, and many are still ongoing (714 studies, 349 completed), as well as the effects of GSH supplementation (162 studies, 100 completed) ( ).…”

Section: Treatment With Gsh and Thiolsmentioning

confidence: 99%

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

2020

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The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease.

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Section: Treatment With Gsh and Thiolsmentioning

confidence: 99%

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

2020

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“…Many intestinal disorders present their etiopathogenesis linked to interactions between altered intestinal permeability and luminal exogenous agents, as well as secretory products of the mucosa itself ( Alhamoruni et al, 2012 ). In recent years, several studies had underlined the involvement of the oxidative stress as well as immune activation as major contributing factors to tissue injury, together with alteration in epithelial permeability that leads to increased and long-lasting exposure of the mucosa to antigens, cytokines, and ROS, inducing a permanent status of inflammation ( Moura et al, 2015 ; Bourgonje et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Abnormally high levels of ROS are produced in IBD and could be a major contributing factor to tissue injury ( Zhu and Li 2012 ; Bourgonje et al, 2020 ). The administration of antioxidants with additional anti-inflammatory properties may be beneficial in the treatment of IBD; thus, we tested the potentiality of Cannabis extract and its main constituents to modulate ROS levels of cells monolayer.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Isolated From Cannabis sativa L. Protects Intestinal Barrier From In Vitro Inflammation and Oxidative Stress

et al. 2021

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The relevance and incidence of intestinal bowel diseases (IBD) have been increasing over the last 50 years and the current therapies are characterized by severe side effects, making essential the development of new strategies that combine efficacy and safety in the management of human IBD. Herbal products are highly considered in research aimed at discovering new approaches for IBD therapy and, among others, Cannabis sativa L. has been traditionally used for centuries as an analgesic and anti-inflammatory remedy also in different gastrointestinal disorders. This study aims to investigate the effects of different C. sativa isolated compounds in an in vitro model of intestinal epithelium. The ability of treatments to modulate markers of intestinal dysfunctions was tested on Caco-2 intestinal cell monolayers. Our results, obtained by evaluation of ROS production, TEER and paracellular permeability measurements and tight junctions evaluation show Cannabidiol as the most promising compound against intestinal inflammatory condition. Cannabidiol is able to inhibit ROS production and restore epithelial permeability during inflammatory and oxidative stress conditions, suggesting its possible application as adjuvant in IBD management.

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“…An imbalance in proinflammatory and anti-inflammatory cytokine levels was shown to occur in CD [2,6]. Similarly, plasma antioxidant defenses are diminished in CD [7].…”

Section: Introductionmentioning

confidence: 96%

“…Mitochondrial dysfunction could therefore involve a combination of excess ROS production and diminished antioxidant capacity. Oxidative stress leads to mucosal layer damage and bacterial invasion, which in turn further stimulate the immune response and contribute to disease progression [7]. Environmental factors and oxidative stress can affect the disease through epigenetics.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress in the Pathogenesis of Crohn’s Disease and the Interconnection with Immunological Response, Microbiota, External Environmental Factors, and Epigenetics

et al. 2021

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Inflammatory bowel disease (IBD) is a complex multifactorial disorder in which external and environmental factors have a large influence on its onset and development, especially in genetically susceptible individuals. Crohn’s disease (CD), one of the two types of IBD, is characterized by transmural inflammation, which is most frequently located in the region of the terminal ileum. Oxidative stress, caused by an overabundance of reactive oxygen species, is present locally and systemically in patients with CD and appears to be associated with the well-described imbalanced immune response and dysbiosis in the disease. Oxidative stress could also underlie some of the environmental risk factors proposed for CD. Although the exact etiopathology of CD remains unknown, the key role of oxidative stress in the pathogenesis of CD is extensively recognized. Epigenetics can provide a link between environmental factors and genetics, and numerous epigenetic changes associated with certain environmental risk factors, microbiota, and inflammation are reported in CD. Further attention needs to be focused on whether these epigenetic changes also have a primary role in the pathogenesis of CD, along with oxidative stress.

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Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease

Cited by 196 publications

References 92 publications

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

Cannabidiol Isolated From Cannabis sativa L. Protects Intestinal Barrier From In Vitro Inflammation and Oxidative Stress

Oxidative Stress in the Pathogenesis of Crohn’s Disease and the Interconnection with Immunological Response, Microbiota, External Environmental Factors, and Epigenetics

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