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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Research Article

Changes of Colon in Rats with Different Ages in Response to Lipopolysaccharide

Author(s): Yanli Li, Yuhui Guo, Liu Aoqi, Chengquan Ma, Zhengguo Xiong, Ding Yuan, Changcheng Zhang, Jihong Zhang* and Yaoyan Dun*

Volume 30, Issue 39, 2023

Published on: 10 February, 2023

Page: [4492 - 4503] Pages: 12

DOI: 10.2174/0929867330666230113112803

Price: $65

Abstract

Background: Lipopolysaccharide (LPS) is an endotoxin that causes inflammation, and the content of LPS increases gradually during the process of aging. Whether the response of the colon to LPS stimulation will increase with age is yet unknown.

Objective: The study investigated the effects of LPS stimulation on the colon of adult and aging rats.

Method: 43 healthy male SD rats were divided into 4 different groups: adult group and LPS-stimulated adult group at the age of 4 months, and aging group and LPS-stimulated aging group at the age of 22 months. Rats were stimulated by intraperitoneal injection of LPS (1mg/kg) for 24 h. The morphological changes of the colon were observed, and intestinal inflammatory response, tight junction proteins, apoptosis, and proliferation in intestinal epithelial cells were detected.

Results: A series of morphology changes occurred in the colon of adult rats after LPS stimulation, the higher inflammatory response (TLR4, NF-κB, and IL-1β), changes in the protein levels of tight junctions (ZO-1, Claudin1, and Claudin2), and increased apoptosis (Bax, Bcl2) and proliferation (PCNA) of intestinal epithelial cells. The above changes were also found in aging rats. LPS stimulation further promotes the above changes to some extent in the colon of aging rats.

Conclusion: A series of colon changes in rats was significantly damaged during LPS stimulation and aging, and these changes were further aggravated to some extent in LPS-stimulated aging rats.

Keywords: LPS, aging, inflammation, tight junction, apoptosis, intestinal epithelial cells.

« Previous
[1]
Groschwitz, K.R.; Hogan, S.P. Intestinal barrier function: Molecular regulation and disease pathogenesis. J. Allergy Clin. Immunol., 2009, 124(1), 3-20.
[http://dx.doi.org/10.1016/j.jaci.2009.05.038] [PMID: 19560575]
[2]
Su, L.; Nalle, S.C.; Shen, L.; Turner, E.S.; Singh, G.; Breskin, L.A.; Khramtsova, E.A.; Khramtsova, G.; Tsai, P.Y.; Fu, Y.X.; Abraham, C.; Turner, J.R. TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology, 2013, 145(2), 407-415.
[http://dx.doi.org/10.1053/j.gastro.2013.04.011] [PMID: 23619146]
[3]
Tran, L.; Greenwood-Van Meerveld, B. Age-associated remodeling of the intestinal epithelial barrier. J. Gerontol. A Biol. Sci. Med. Sci., 2013, 68(9), 1045-1056.
[http://dx.doi.org/10.1093/gerona/glt106] [PMID: 23873964]
[4]
Zeisel, M.B.; Dhawan, P.; Baumert, T.F. Tight junction proteins in gastrointestinal and liver disease. Gut, 2019, 68(3), 547-561.
[http://dx.doi.org/10.1136/gutjnl-2018-316906] [PMID: 30297438]
[5]
Chen, P.; Stärkel, P.; Turner, J.R.; Ho, S.B.; Schnabl, B. Dysbiosis induced intestinal inflammation activates tumor necrosis factor receptor I and mediates alcoholic liver disease in mice. Hepatology, 2015, 61(3), 883-894.
[http://dx.doi.org/10.1002/hep.27489] [PMID: 25251280]
[6]
Branca, J.J.V.; Gulisano, M.; Nicoletti, C. Intestinal epithelial barrier functions in ageing. Ageing Res. Rev., 2019, 54, 100938.
[http://dx.doi.org/10.1016/j.arr.2019.100938] [PMID: 31369869]
[7]
Cerqueira César Machado, M.; Pinheiro da Silva, F. Intestinal barrier dysfunction in human pathology and aging. Curr. Pharm. Des., 2016, 22(30), 4645-4650.
[http://dx.doi.org/10.2174/1381612822666160510125331] [PMID: 27160754]
[8]
Roth, S.; Franken, P.; Sacchetti, A.; Kremer, A.; Anderson, K.; Sansom, O.; Fodde, R. Paneth cells in intestinal homeostasis and tissue injury. PLoS One, 2012, 7(6), e38965.
[http://dx.doi.org/10.1371/journal.pone.0038965] [PMID: 22745693]
[9]
Gehart, H.; Clevers, H. Tales from the crypt: New insights into intestinal stem cells. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(1), 19-34.
[http://dx.doi.org/10.1038/s41575-018-0081-y] [PMID: 30429586]
[10]
Gong, Q.; He, L.; Wang, M.; Zuo, S.; Gao, H.; Feng, Y.; Du, L.; Luo, Y.; Li, J. Comparison of the TLR4/NFκB and NLRP3 signalling pathways in major organs of the mouse after intravenous injection of lipopolysaccharide. Pharm. Biol., 2019, 57(1), 555-563.
[http://dx.doi.org/10.1080/13880209.2019.1653326] [PMID: 31446815]
[11]
Hersoug, L.G.; Møller, P.; Loft, S. Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation, adipocyte size and pyroptosis during obesity. Nutr. Res. Rev., 2018, 31(2), 153-163.
[http://dx.doi.org/10.1017/S0954422417000269] [PMID: 29362018]
[12]
Cao, S.; Zhang, Q.; Wang, C.; Wu, H.; Jiao, L.; Hong, Q.; Hu, C. LPS challenge increased intestinal permeability, disrupted mitochondrial function and triggered mitophagy of piglets. Innate Immun., 2018, 24(4), 221-230.
[http://dx.doi.org/10.1177/1753425918769372] [PMID: 29642727]
[13]
Guerville, M.; Boudry, G. Gastrointestinal and hepatic mechanisms limiting entry and dissemination of lipopolysaccharide into the systemic circulation. Am. J. Physiol. Gastrointest. Liver Physiol., 2016, 311(1), G1-G15.
[http://dx.doi.org/10.1152/ajpgi.00098.2016] [PMID: 27151941]
[14]
Steimle, A.; Michaelis, L.; Di Lorenzo, F.; Kliem, T.; Münzner, T.; Maerz, J.K.; Schäfer, A.; Lange, A.; Parusel, R.; Gronbach, K.; Fuchs, K.; Silipo, A.; Öz, H.H.; Pichler, B.J.; Autenrieth, I.B.; Molinaro, A.; Frick, J.S. Weak agonistic LPS restores intestinal immune homeostasis. Mol. Ther., 2019, 27(11), 1974-1991.
[http://dx.doi.org/10.1016/j.ymthe.2019.07.007] [PMID: 31416777]
[15]
Guo, S.; Nighot, M.; Al-Sadi, R.; Alhmoud, T.; Nighot, P.; Ma, T.Y. Lipopolysaccharide regulation of intestinal tight junction permeability is mediated by TLR4 signal transduction pathway activation of FAK and MyD88. J. Immunol., 2015, 195(10), 4999-5010.
[http://dx.doi.org/10.4049/jimmunol.1402598] [PMID: 26466961]
[16]
Li, L.; Wan, G.; Han, B.; Zhang, Z. Echinacoside alleviated LPS-induced cell apoptosis and inflammation in rat intestine epithelial cells by inhibiting the mTOR/STAT3 pathway. Biomed. Pharmacother., 2018, 104, 622-628.
[http://dx.doi.org/10.1016/j.biopha.2018.05.072] [PMID: 29803175]
[17]
Lee, S.M.; Kim, N.; Yoon, H.; Nam, R.H.; Lee, D.H. Microbial changes and host response in F344 rat colon depending on sex and age following a high-fat diet. Front. Microbiol., 2018, 9(9), 2236.
[http://dx.doi.org/10.3389/fmicb.2018.02236] [PMID: 30298061]
[18]
Moorefield, E.C.; Andres, S.F.; Blue, R.E.; Van Landeghem, L.; Mah, A.T.; Santoro, M.A.; Ding, S. Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells. Aging, 2017, 9(8), 1898-1915.
[http://dx.doi.org/10.18632/aging.101279] [PMID: 28854151]
[19]
Kim, K.A.; Jeong, J.J.; Yoo, S.Y.; Kim, D.H. Gut microbiota lipopolysaccharide accelerates inflamm-aging in mice. BMC Microbiol., 2016, 16(1), 9.
[http://dx.doi.org/10.1186/s12866-016-0625-7] [PMID: 26772806]
[20]
Ren, W.; Wu, K.; Li, X.; Luo, M.; Liu, H.; Zhang, S.; Hu, Y. Age-related changes in small intestinal mucosa epithelium architecture and epithelial tight junction in rat models. Aging Clin. Exp. Res., 2014, 26(2), 183-191.
[http://dx.doi.org/10.1007/s40520-013-0148-0] [PMID: 24243034]
[21]
Jo, H.J.; Kim, N.; Nam, R.H.; Kang, J.M.; Kim, J.H.; Choe, G.; Lee, H.S.; Park, J.H.; Chang, H.; Kim, H.; Lee, M.Y.; Kim, Y.S.; Kim, J.S.; Jung, H.C. Fat deposition in the tunica muscularis and decrease of interstitial cells of Cajal and nNOS-positive neuronal cells in the aged rat colon. Am. J. Physiol. Gastrointest. Liver Physiol., 2014, 306(8), G659-G669.
[http://dx.doi.org/10.1152/ajpgi.00304.2012] [PMID: 24525022]
[22]
Phillips, R.J.; Pairitz, J.C.; Powley, T.L. Age-related neuronal loss in the submucosal plexus of the colon of Fischer 344 rats. Neurobiol. Aging, 2007, 28(7), 1124-1137.
[http://dx.doi.org/10.1016/j.neurobiolaging.2006.05.019] [PMID: 16793176]
[23]
Phillips, R.J.; Rhodes, B.S.; Powley, T.L. Effects of age on sympathetic innervation of the myenteric plexus and gastrointestinal smooth muscle of Fischer 344 rats. Anat. Embryol., 2006, 211(6), 673-683.
[http://dx.doi.org/10.1007/s00429-006-0123-z] [PMID: 17024301]
[24]
Patankar, J.V.; Becker, C. Cell death in the gut epithelium and implications for chronic inflammation. Nat. Rev. Gastroenterol. Hepatol., 2020, 17(9), 543-556.
[http://dx.doi.org/10.1038/s41575-020-0326-4] [PMID: 32651553]
[25]
Dun, Y.; Liu, M.; Chen, J.; Peng, D.; Zhao, H.; Zhou, Z.; Wang, T.; Liu, C.; Guo, Y.; Zhang, C.; Yuan, D. Panax japonicusRegulatory effects of saponins from on colonic epithelial tight junctions in aging rats. J. Ginseng Res., 2018, 42(1), 50-56.
[http://dx.doi.org/10.1016/j.jgr.2016.12.011] [PMID: 29348722]
[26]
Wang, J.; Ghosh, S.S.; Ghosh, S. Curcumin improves intestinal barrier function: Modulation of intracellular signaling, and organization of tight junctions. Am. J. Physiol. Cell Physiol., 2017, 312(4), C438-C445.
[http://dx.doi.org/10.1152/ajpcell.00235.2016] [PMID: 28249988]
[27]
Marchiando, A.M.; Shen, L.; Graham, W.V.; Edelblum, K.L.; Duckworth, C.A.; Guan, Y.; Montrose, M.H.; Turner, J.R.; Watson, A.J.M. The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding. Gastroenterology, 2011, 140(4), 1208-1218.
[http://dx.doi.org/10.1053/j.gastro.2011.01.004] [PMID: 21237166]
[28]
Rawat, M.; Nighot, M.; Al-Sadi, R.; Gupta, Y.; Viszwapriya, D.; Yochum, G.; Koltun, W.; Ma, T.Y. IL1B increases intestinal tight junction permeability by up-regulation of MIR200C-3p, which degrades occludin mRNA. Gastroenterology, 2020, 159(4), 1375-1389.
[http://dx.doi.org/10.1053/j.gastro.2020.06.038] [PMID: 32569770]
[29]
Zhang, Y.; Zhou, F.; Wang, Z.; Li, Z.; Li, J. PNU-282987 attenuates intestinal epithelial barrier dysfunction in LPS-induced endotoxemia. Inflammation, 2020, 43(2), 417-424.
[http://dx.doi.org/10.1007/s10753-019-01096-w] [PMID: 31950323]
[30]
Xie, M.Y.; Hou, L.J.; Sun, J.J.; Zeng, B.; Xi, Q.Y.; Luo, J.Y.; Chen, T.; Zhang, Y.L. Porcine milk exosome MiRNAs attenuate LPS-induced apoptosis through inhibiting TLR4/NF-κB and p53 pathways in intestinal epithelial cells. J. Agric. Food Chem., 2019, 67(34), 9477-9491.
[http://dx.doi.org/10.1021/acs.jafc.9b02925] [PMID: 31429552]
[31]
Murphy, J.R. Host defenses in murine malaria: Immunological characteristics of a protracted state of immunity to Plasmodium yoelii. Infect. Immun., 1980, 27(1), 68-74.
[http://dx.doi.org/10.1128/iai.27.1.68-74.1980] [PMID: 6987179]

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