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

Document Type : Original Article

Author

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

Abstract

Objective(s): 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.

Keywords

References

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a common food toxin related to physiological functions and health. Physiol Res. 2017; 66(2):205-217.
Zamani E, Shokrzadeh M, Ziar A, Abedian-Kenari S, Shaki F. Acrylamide attenuated immune tissues’ function via induction of apoptosis and oxidative stress: Protection by l-carnitine. Hum Exp Toxicol 2018; 37(8):859-869.
Tabeshpour J, Mehri S, Abnous K, Hosseinzadeh H. Role of Oxidative Stress, MAPKinase and Apoptosis Pathways in the Protective Effects of Thymoquinone Against Acrylamide-Induced Central Nervous System Toxicity in Rat. Neurochem Res 2020; 45(2):254-267.
Amirshahrokhi K, Khalili AR. Methylsulfonylmethane is effective against gastric mucosal injury. Eur J Pharmacol 2017; 811:240-248.
Yasukawa K, Tokuda H, Tun X, Utsumi H, Yamada K. The detrimental effect of nitric oxide on tissue is associated with inflammatory events in the vascular endothelium and neutrophils in mice with dextran sodium sulfate-induced colitis. Free Radic Res 2012; 46(12):1427-36.
Akazawa Y, Kubo M, Zhang R, Matsumoto K, Yan F, Setiawan H, et al. Inhibition of arginase ameliorates experimental ulcerative colitis in mice. Free Radic Res 2013; 47(3):137-45.
Sklyarov AY, Panasyuk NB, Fomenko IS. Role of nitric oxide-synthase and cyclooxygenase/lipooxygenase systems in development of experimental ulcerative colitis. J Physiol Pharmacol 2011; 62(1):65-73.
Wei Q, Li J, Li X, Zhang L, Shi F. Reproductive toxicity in acrylamide-treated female mice. Reprod Toxicol 2014; 46:121-8.
Marković J, Stošić M, Kojić D, Matavulj M. Effects of acrylamide on oxidant/antioxidant parameters and CYP2E1 expression in rat pancreatic endocrine cells. Acta Histochem 2018; 120(2):73-83.
Fournier BM, Parkos CA. The role of neutrophils during intestinal inflammation. Mucosal Immunol 2012; 5(4):354-66.
Zhou GX, Liu ZJ. Potential roles of neutrophils in regulating intestinal mucosal inflammation of inflammatory bowel disease. J Dig Dis 2017; 18(9):495-503.
Gong Z, Zhao S, Zhou J, Yan J, Wang L, Du X, et al. Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production. Mol Immunol 2018; 104:11-19.
Singh UP, Singh NP, Murphy EA, Price RL, Fayad R, Nagarkatti M, et al. Chemokine and cytokine levels in inflammatory bowel disease patients. Cytokine 2016; 77:44-9.
Chen M, Gao L, Chen P, Feng D, Jiang Y, Chang Y, et al. Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon. Mediators Inflamm 2016; 2016:5359768.
de Bruyn M, Vandooren J, Ugarte-Berzal E, Arijs I, Vermeire S, Opdenakker G. The molecular biology of matrix metalloproteinases and tissue inhibitors of metalloproteinases in inflammatory bowel diseases. Crit Rev Biochem Mol Biol 2016; 51(5):295-358.
Parker A, Vaux L, Patterson AM, Modasia A, Muraro D, Fletcher AG, et al. Elevated apoptosis impairs epithelial cell turnover and shortens villi in TNF-driven intestinal inflammation. Cell Death Dis 2019; 10(2):108.
Becker C, Watson AJ, Neurath MF. Complex roles of caspases in the pathogenesis of inflammatory bowel disease. Gastroenterology 2013; 144(2):283-93.
Arafa EA, Mohamed WR, Zaher DM, Omar HA. Gliclazide attenuates acetic acid-induced colitis via the modulation of PPARγ, NF-κB and MAPK signaling pathways. Toxicol Appl Pharmacol 2020; 391:114919.
Shi L, Dai Y, Jia B, Han Y, Guo Y, Xie T, et al. The inhibitory effects of Qingchang Wenzhong granule on the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium-induced colitis. J Cell Biochem 2019; 120(6):9979-9991.
Novak EA, Mollen KP. Mitochondrial dysfunction in inflammatory bowel disease. Front Cell Dev Biol. 2015 Oct 1;3:62.
Wang Z, Li S, Cao Y, Tian X, Zeng R, Liao DF, et al. Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer. Oxid Med Cell Longev 2016; 2016:9875298.
Jiang G, Zhang L, Wang H, Chen Q, Wu X, Yan X, et al. Protective effects of a Ganoderma atrum polysaccharide against acrylamide induced oxidative damage via a mitochondria mediated intrinsic apoptotic pathway in IEC-6 cells. Food Funct 2018; 9(2):1133-1143.
Sengul E, Gelen V, Yildirim S, Tekin S, Dag Y. The Effects of Selenium in Acrylamide-Induced Nephrotoxicity in Rats: Roles of Oxidative Stress, Inflammation, Apoptosis, and DNA Damage. Biol Trace Elem Res 2020.
Atreya I, Atreya R, Neurath MF. NF-kappaB in inflammatory bowel disease. J Intern Med 2008; 263(6):591-6.
Andresen L, Jørgensen VL, Perner A, Hansen A, Eugen-Olsen J, Rask-Madsen J. Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis. Gut 2005; 54(4):503-9.
Zhao M, Lewis Wang FS, Hu X, Chen F, Chan HM. Acrylamide-induced neurotoxicity in primary astrocytes and microglia: Roles of the Nrf2-ARE and NF-κB pathways. Food Chem Toxicol 2017; 106(Pt A):25-35.
Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014; 14(5):329-42.
Wang L, Walia B, Evans J, Gewirtz AT, Merlin D, Sitaraman SV. IL-6 induces NF-kappa B activation in the intestinal epithelia. J Immunol 2003; 171(6):3194-201.
Shouval DS, Ouahed J, Biswas A, Goettel JA, Horwitz BH, Klein C, et al.  Interleukin 10 receptor signaling: master regulator of intestinal mucosal homeostasis in mice and humans. Adv Immunol 2014; 122:177-210.
Elhelaly AE, AlBasher G, Alfarraj S, Almeer R, Bahbah EI, Fouda MMA, et al.  Protective effects of hesperidin and diosmin against acrylamide-induced liver, kidney, and brain oxidative damage in rats. Environ Sci Pollut Res Int 2019; 26(34):35151-35162.

Iranian Journal of Basic Medical Sciences
Volume 24, Issue 3
March 2021
Pages 312-321

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