丙烯酰胺暴露通过激活核因子κB、炎性细胞因子、诱导型一氧化氮合酶和氧化应激加重小鼠溃疡性结肠炎的发展。

Acrylamide exposure aggravates the development of ulcerative colitis in mice through activation of NF-κB, inflammatory cytokines, iNOS, and oxidative stress.

作者信息

Amirshahrokhi Keyvan

机构信息

Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.

出版信息

Iran J Basic Med Sci. 2021 Mar;24(3):312-321. doi: 10.22038/ijbms.2021.52233.11816.

Abstract

OBJECTIVES

Acrylamide is a toxic compound that forms during food processing at high temperatures. Acrylamide has been shown to induce toxicity in various organs in the body. This study aimed to investigate the effect of acrylamide exposure on the susceptibility of the colon to ulcerative colitis in a mouse model.

MATERIALS AND METHODS

Mice were pretreated with acrylamide (oral, 20 and 30 mg/kg/day) for 21 consecutive days, and colitis was induced by intrarectal administration of acetic acid.

RESULTS

The results revealed that acrylamide-pretreatment significantly increased disease activity index (DAI), macroscopic damage, histological changes of the colonic mucosa and oxidative stress markers carbonyl protein, malondialdehyde (MDA), and nitric oxide (NO), whereas it decreased the levels of anti-oxidants glutathione (GSH), superoxide dismutase (SOD) and catalase. Moreover, induction of colitis in acrylamide-pretreated mice caused a higher increase in colonic levels of myeloperoxidase (MPO), matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, cytochrome-c, caspase-3, proinflammatory cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and interferon (IFN)-γ, whereas it reduced the level of IL-10. The mRNA expression of nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) were further increased in colon tissue of mice exposed to acrylamide.

CONCLUSION

These findings suggest that acrylamide can accelerate the development of acetic acid-induced colitis. In conclusion, chronic acrylamide exposure may aggravate the severity of ulcerative colitis and increase colonic mucosal damage through oxidative stress and inflammatory responses.

摘要

目的

丙烯酰胺是一种在高温食品加工过程中形成的有毒化合物。已表明丙烯酰胺会在体内各器官诱发毒性。本研究旨在探讨在小鼠模型中丙烯酰胺暴露对结肠患溃疡性结肠炎易感性的影响。

材料与方法

小鼠连续21天经口给予丙烯酰胺(20和30毫克/千克/天)进行预处理,然后通过直肠内注射乙酸诱导结肠炎。

结果

结果显示,丙烯酰胺预处理显著增加了疾病活动指数(DAI)、宏观损伤、结肠黏膜的组织学变化以及氧化应激标志物羰基蛋白、丙二醛(MDA)和一氧化氮(NO),而降低了抗氧化剂谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶的水平。此外,在经丙烯酰胺预处理的小鼠中诱发结肠炎导致结肠中髓过氧化物酶(MPO)、基质金属蛋白酶(MMP)-9、单核细胞趋化蛋白(MCP)-1、细胞色素-c、半胱天冬酶-3、促炎细胞因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-1β和干扰素(IFN)-γ的水平升高幅度更大,而降低了IL-10的水平。在暴露于丙烯酰胺的小鼠结肠组织中,核因子κB(NF-κB)和诱导型一氧化氮合酶(iNOS)的mRNA表达进一步增加。

结论

这些发现表明丙烯酰胺可加速乙酸诱导的结肠炎的发展。总之,长期丙烯酰胺暴露可能会加重溃疡性结肠炎的严重程度,并通过氧化应激和炎症反应增加结肠黏膜损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e639/8087843/291211dfc0a1/IJBMS-24-312-g001.jpg

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