Mesalazine treatment in organotypic culture of celiac patients: Comparative study with gluten free diet

Abstract

Given the central role of gluten in the pathogenesis of celiac disease (CD), a strict gluten-free diet (GFD) is the only validated treatment able to restore epithelium integrity and eliminate risks of complications. The risk of gluten contamination and the persistence of inflammation, even in patients strictly adhering to GFD, may render this treatment not always effective claiming the necessity of different new solutions. Oxidative and nitrosative stress have been indicated to play a pathophysiological role in CD. Mesalazine (5-ASA), a drug largely used in inflammatory bowel disease, has potent antinflammatory and antioxidant effects. In fact, mesalazine has been shown to decrease in vitro gluten induced cytokine response and it has been used in vivo in some refractory condition. However, its effect has never compared to that of GFD. The present study aimed to address this issue by comparing the ability of mesalazine and GFD in treating gluten-induced inflammation and oxidative stress. These effects were studied on duodenal mucosa biopsy cultures from newly diagnosed CD patients, treated or not in vitro with mesalazine, and CD biopsy cultures from patients on gluten-free diet for at least one year; and a cohort of controls constituted by healty subjects. On these models, the antioxidant cellular defences, the PPARγ, NF-kB and NOS2 proteins levels were studied. This study shows that mesalazine is as effective as GFD in reducing oxidative burst and inducing PPARγ expression; moreover it resulted more effective than GFD in decreasing NF-kB and NOS2 to the levels of controls.

Inflammatory Bowel Disease: New Insights into the Interplay between Environmental Factors and PPARγ

“…For example, biopsies from celiac disease patients have been used to investigate the beneficial effect of anti-inflammatory drugs used in IBD treatment. This study demonstrated that mesalazine induces PPARγ expression, inhibiting oxidative and nitrative species' production on OTC [109].…”

New Insights into Non-Dietary Treatment in Celiac Disease: Emerging Therapeutic Options

“…Likewise, mesalazine has been proposed, although it must be remembered that most of these formulations are prepared to be released in the colon and the inflammation in CD affects the small intestine [ 66 ]. Recent studies have shown that mesalazine has a beneficial effect on the molecules and biological mediators of inflammation that occur in the mucosa of celiac patients [ 81 ].…”

Dietary Gluten and Neurodegeneration: A Case for Preclinical Studies

“…Accordingly, reducing chronic inflammation, promoting intestinal mucosal healing and repair, and restoring epithelial barrier integrity and the microbiome are the topmost priorities of the celiac research community. Because PPARγ was described to be the key functional receptor transducing the effects of commonly prescribed anti-inflammatory amino salicylates in inflammatory bowel disease (IBD) patients [65], augmenting PPARγ expression represents a promising approach for the clinical management of gluten induced intestinal inflammation [66]. In this context, mesalazine also known as 5-amino salicylic acid (5-ASA) was shown to reduce oxidative burst and induce PPARγ expression in ex vivo cultures of duodenal biopsies obtained from newly diagnosed celiac patients [66].…”

“…Because PPARγ was described to be the key functional receptor transducing the effects of commonly prescribed anti-inflammatory amino salicylates in inflammatory bowel disease (IBD) patients [65], augmenting PPARγ expression represents a promising approach for the clinical management of gluten induced intestinal inflammation [66]. In this context, mesalazine also known as 5-amino salicylic acid (5-ASA) was shown to reduce oxidative burst and induce PPARγ expression in ex vivo cultures of duodenal biopsies obtained from newly diagnosed celiac patients [66]. In addition, mesalazine treatment also reduced protein levels of nuclear factor kappa B (NFκB) and nitric oxide synthase 2 (NOS2), an enzyme that produces nitric oxide [66].…”

“…In this context, mesalazine also known as 5-amino salicylic acid (5-ASA) was shown to reduce oxidative burst and induce PPARγ expression in ex vivo cultures of duodenal biopsies obtained from newly diagnosed celiac patients [66]. In addition, mesalazine treatment also reduced protein levels of nuclear factor kappa B (NFκB) and nitric oxide synthase 2 (NOS2), an enzyme that produces nitric oxide [66]. Obligate anerobic bacteria have been shown to activate PPARγ signaling to limit the production of nitrate and oxygen electron acceptors by host epithelial cells, thereby preventing the expansion of facultative anerobic bacteria belonging to the family Enterobacteriaceae (phylum Proteobacteria) [59].…”