Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy.
J Cell Physiol. 2018 Jun;233(6):4383-4390. doi: 10.1002/jcp.26217. Epub 2018 Jan 4.
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.
鉴于 gluten 在乳糜泻（CD）发病机制中的核心作用，严格的无麸质饮食（GFD）是唯一经过验证的治疗方法，能够恢复肠上皮完整性并消除并发症风险。即使在严格遵循 GFD 的患者中，也存在 gluten 污染和炎症持续存在的风险，这可能使这种治疗方法并不总是有效，需要寻求不同的新解决方案。氧化应激和硝化应激已被证明在 CD 中发挥病理生理作用。美沙拉嗪（5-ASA）是一种广泛用于炎症性肠病的药物，具有强大的抗炎和抗氧化作用。事实上，美沙拉嗪已被证明可以减少体外 gluten 诱导的细胞因子反应，并且已在一些难治性疾病中体内使用。然而，它的效果从未与 GFD 的效果进行过比较。本研究旨在通过比较美沙拉嗪和 GFD 在治疗 gluten 诱导的炎症和氧化应激方面的能力来解决这个问题。这些作用是在新诊断的 CD 患者的十二指肠粘膜活检培养物中研究的，这些患者在体外用美沙拉嗪治疗或未治疗，以及在无麸质饮食至少一年的 CD 活检培养物中研究；并由健康受试者组成的对照组。在这些模型中，研究了抗氧化细胞防御、PPARγ、NF-kB 和 NOS2 蛋白水平。这项研究表明，美沙拉嗪与 GFD 一样有效，可以减少氧化爆发并诱导 PPARγ 表达；此外，它比 GFD 更有效地降低 NF-kB 和 NOS2 至对照组的水平。
