{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:16:30Z","timestamp":1792271790895,"version":"4.4.0"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,24]],"date-time":"2021-01-24T00:00:00Z","timestamp":1611446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007065","name":"University of Salerno","doi-asserted-by":"publisher","award":["(FARB 2018-ORSA180779 and FARB 2019-ORSA180779) in favor of M.S."],"award-info":[{"award-number":["(FARB 2018-ORSA180779 and FARB 2019-ORSA180779) in favor of M.S."]}],"id":[{"id":"10.13039\/501100007065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The intestines are recognized as the main source of chronic inflammation in chronic kidney disease (CKD) and, among other cells, macrophages are involved in modulating this process as well as in the impaired immune response which also occurs in CKD patients. In this study, we evaluated the effect of Indoxyl Sulfate (IS), a protein bound uremic toxin poorly eliminated by hemodialysis, on inflammatory, oxidative stress and pro-apoptotic parameters, at the intestinal level in mice, on intestinal epithelial cells (IEC-6) and on primary murine peritoneal macrophages. C57BL\/6J mice were treated with IS (800 mg\/kg i.p.) for 3 or 6 h and histopathological analysis showed that IS induced intestinal inflammation and increased cyclooxygenase-2 (COX-2), nitrotyrosine and Bax expression in intestinal tissue. In IEC-6 cells, IS (125\u20131000 \u00b5M) increased tumor necrosis factor-\u03b1 levels, COX-2 and inducible nitric oxide synthase expression and nitrotyrosine formation. Moreover, IS increased pro-oxidant, pro-inflammatory and pro-apoptotic parameters in peritoneal macrophages from IS-treated mice. Also, the serum concentration of IS and pro-inflammatory levels of cytokines resulted increased in IS-treated mice. Our results indicate that IS significantly contributes to affect intestinal homeostasis, immune response, and to induce a systemic pro-inflammatory state thus highlighting its potential role as therapeutic target in CKD patients.<\/jats:p>","DOI":"10.3390\/ijms22031135","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T02:07:00Z","timestamp":1611540420000},"page":"1135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Pro-Inflammatory Effects of Indoxyl Sulfate in Mice: Impairment of Intestinal Homeostasis and Immune Response"],"prefix":"10.3390","volume":"22","author":[{"given":"Shara Francesca","family":"Rapa","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-1239","authenticated-orcid":false,"given":"Francesco","family":"Prisco","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Napoli, NA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9843-8443","authenticated-orcid":false,"given":"Ada","family":"Popolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Iovane","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-9489","authenticated-orcid":false,"given":"Giuseppina","family":"Autore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2779-4181","authenticated-orcid":false,"given":"Biagio Raffaele","family":"Di Iorio","sequence":"additional","affiliation":[{"name":"UOC Nephrology AORN \u201cSan Giuseppe Moscati\u201d, C.da Amoretta, 83100 Avellino, AV, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Dal Piaz","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando","family":"Paciello","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Napoli, NA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyu","family":"Nishijima","sequence":"additional","affiliation":[{"name":"Pharmaceuticals Division, Kureha Corporation, Tokyo 169-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2333-1630","authenticated-orcid":false,"given":"Stefania","family":"Marzocco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1038\/ki.2008.516","article-title":"Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease","volume":"111","author":"Cachofeiro","year":"2008","journal-title":"Kidney Int. Suppl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1440-1797.2006.00541.x","article-title":"Inflammation in end-stage renal disease: The hidden enemy","volume":"11","author":"Stenvinkel","year":"2006","journal-title":"Nephrology (Carlton)"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/ki.2012.439","article-title":"Targeting Nrf2 activation to ameliorate oxidative stress and inflammation in Chronic Kidney Disease","volume":"83","author":"Ruiz","year":"2013","journal-title":"Kidney Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.2215\/CJN.02720409","article-title":"Persistent inflammation as a catalyst for other risk factors in chronic kidney disease: A hypothesis proposal","volume":"4","author":"Carrero","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.semnephrol.2012.12.011","article-title":"Clinical detection, risk factors, and cardiovascular consequences of medial arterial calcification: A pattern of vascular injury associated with aberrant mineral metabolism","volume":"33","author":"Lau","year":"2013","journal-title":"Semin. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1525-139X.2010.00784.x","article-title":"Inflammation in end-stage renal disease\u2013what have we learned in 10 years?","volume":"23","author":"Carrero","year":"2010","journal-title":"Semin. Dial."},{"key":"ref_7","first-page":"2180373","article-title":"Inflammation and Chronic Kidney Disease: Current Approaches and Recent Advances","volume":"2018","author":"Mihai","year":"2018","journal-title":"Kidney Dis. Pathophysiol. Clin. Improv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000381990","article-title":"The gut as a source of inflammation in chronic kidney disease","volume":"130","author":"Lau","year":"2015","journal-title":"Nephron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1007\/s10620-014-3202-7","article-title":"Gut bacterial translocation may aggravate microinflammation in hemodialysis patients","volume":"59","author":"Shi","year":"2014","journal-title":"Dig. Dis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1053\/j.jrn.2011.05.004","article-title":"Examining associations of circulating endotoxin with nutritional status, inflammation, and mortality in hemodialysis patients","volume":"22","author":"Feroze","year":"2012","journal-title":"J. Ren. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"431","DOI":"10.2215\/CJN.03600807","article-title":"Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients","volume":"3","author":"Szeto","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2215\/CJN.04610510","article-title":"Circulating endotoxemia: A novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease","volume":"6","author":"McIntyre","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/ki.2012.440","article-title":"The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease","volume":"83","author":"Anders","year":"2013","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"962","DOI":"10.3390\/toxins4110962","article-title":"Immune Dysfunction in Uremia\u2014An Update","volume":"4","author":"Cohen","year":"2012","journal-title":"Toxins"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0024-3205(99)00355-0","article-title":"In vitro and in vivo TNF\u03b1 synthesis by methylguanidine, an uremic catabolyte","volume":"65","author":"Autore","year":"1999","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ejphar.2003.11.011","article-title":"Effect of methylguanidine in carrageenan-induced acute inflammation in the rats","volume":"484","author":"Marzocco","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.lfs.2004.02.031","article-title":"Methylguanidine reduces the development of non septic shock induced by zymosan in mice","volume":"75","author":"Marzocco","year":"2004","journal-title":"Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1080\/10715760410001725517","article-title":"Effect of methylguanidine in a model of septic shock induced by LPS","volume":"38","author":"Marzocco","year":"2004","journal-title":"Free Radic. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.neuint.2010.06.016","article-title":"Pro-apoptotic effect of methylguanidine on hydrogen peroxide-treated rat glioma cell line","volume":"57","author":"Marzocco","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2215\/CJN.03980609","article-title":"Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients","volume":"4","author":"Barreto","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1053\/j.jrn.2010.05.002","article-title":"Indoxyl sulfate is a nephro-vascular toxin","volume":"20","author":"Niwa","year":"2010","journal-title":"J. Ren. Nutr."},{"key":"ref_22","first-page":"96","article-title":"Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis","volume":"124","author":"Niwa","year":"1994","journal-title":"J. Lab. Clin. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000330852","article-title":"Indoxyl sulfate induces epithelial-to-mesenchymal transition in rat kidneys and human proximal tubular cells","volume":"34","author":"Bolati","year":"2011","journal-title":"Am. J. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fphar.2017.00370","article-title":"Indoxyl Sulfate Affects Glial Function Increasing Oxidative Stress and Neuroinflammation in Chronic Kidney Disease: Interaction between Astrocytes and Microglia","volume":"12","author":"Adesso","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Adesso, S., Paterniti, I., Cuzzocrea, S., Fujioka, M., Autore, G., Magnus, T., Pinto, A., and Marzocco, S. (2018). AST-120 Reduces Neuroinflammation Induced by Indoxyl Sulfate in Glial Cells. J. Clin. Med., 7.","DOI":"10.3390\/jcm7100365"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Adesso, S., Ruocco, M., Rapa, S.F., Piaz, F.D., Di Iorio, B.R., Popolo, A., Autore, G., Nishijima, F., Pinto, A., and Marzocco, S. (2019). Effect of Indoxyl Sulfate on the Repair and Intactness of Intestinal Epithelial Cells: Role of Reactive Oxygen Species\u2019 Release. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092280"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Adesso, S., Popolo, A., Bianco, G., Sorrentino, R., Pinto, A., Autore, G., and Marzocco, S. (2013). The uremic toxin indoxyl sulphate enhances macrophage response to LPS. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076778"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2180373","DOI":"10.1155\/2018\/2180373","article-title":"Inflammation-Related Mechanisms in Chronic Kidney Disease Prediction, Progression, and Outcome","volume":"2018","author":"Mihai","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1159\/000346628","article-title":"Very low protein diet reduces indoxyl sulfate levels in chronic kidney disease","volume":"35","author":"Marzocco","year":"2013","journal-title":"Blood Purif."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rapa, S.F., Di Iorio, B.R., Campiglia, P., Heidland, A., and Marzocco, S. (2020). Inflammation and Oxidative Stress in Chronic Kidney Disease-Potential Therapeutic Role of Minerals, Vitamins and Plant-Derived Metabolites. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010263"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/ndt\/gfy164","article-title":"Vegetarian diets and chronic kidney disease","volume":"34","author":"Chauveau","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Di Iorio, B.R., Rocchetti, M.T., De Angelis, M., Cosola, C., Marzocco, S., Di Micco, L., di Bari, I., Accetturo, M., Vacca, M., and Gobbetti, M. (2019). Nutritional Therapy Modulates Intestinal Microbiota and Reduces Serum Levels of Total and Free Indoxyl Sulfate and P-Cresyl Sulfate in Chronic Kidney Disease (Medika Study). J. Clin. Med., 8.","DOI":"10.3390\/jcm8091424"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Marzocco, S., Fazeli, G., Di Micco, L., Autore, G., Adesso, S., Dal Piaz, F., Heidland, A., and Di Iorio, B. (2018). Supplementation of Short-Chain Fatty Acid, Sodium Propionate, in Patients on Maintenance hemodialysis-\"Beneficial Effects on Inflammatory Parameters and Gut-Derived Uremic Toxins\"-A Pilot Study (PLAN Study). J. Clin. Med., 7.","DOI":"10.3390\/jcm7100315"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ichii, O., Otsuka-Kanazawa, S., Nakamura, T., Ueno, M., Kon, Y., Chen, W., Rosenberg, A.Z., and Kopp, J.B. (2014). Podocyte injury caused by indoxyl sulfate, a uremic toxin and aryl-hydrocarbon receptor ligand. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108448"},{"key":"ref_35","first-page":"608","article-title":"Pathology of gastrointestinal tract in chronic hemodialysis patients: An autopsy study of 78 cases","volume":"80","author":"Vaziri","year":"1985","journal-title":"Am. J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6720575","DOI":"10.1155\/2016\/6720575","article-title":"Chronic Kidney Disease Induced Intestinal Mucosal Barrier Damage Associated with Intestinal Oxidative Stress Injury","volume":"2016","author":"Yu","year":"2016","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s10620-014-3428-4","article-title":"Role of Nrf2 dysfunction in uremia-associated intestinal inflammation and epithelial barrier disruption","volume":"60","author":"Lau","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/ndt\/gfy238","article-title":"Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression","volume":"34","author":"Gonzalez","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/MNH.0000000000000565","article-title":"Microbiome modulation to correct uremic toxins and to preserve kidney functions","volume":"29","author":"Caggiano","year":"2020","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"573685","DOI":"10.1155\/2014\/573685","article-title":"Peritoneal Membrane Injury and Peritoneal Dialysis","volume":"2014","author":"Chugh","year":"2014","journal-title":"Adv. Nephrol."},{"key":"ref_41","first-page":"S34","article-title":"Clinical outcomes and peritoneal histology in patients starting peritoneal dialysis are related to diabetic status and serum albumin levels","volume":"108","author":"Soto","year":"2008","journal-title":"Kidney Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.dld.2009.04.010","article-title":"Heterogeneous expression of cyclooxygenase-2 and inducible nitric oxide synthase within colorectal tumors: Correlation with tumor angiogenesis","volume":"42","author":"Cianchi","year":"2010","journal-title":"Dig. Liver Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/onc.2009.421","article-title":"The Role of COX-2 in Intestinal Inflammation and Colorectal Cancer","volume":"29","author":"Wang","year":"2010","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000481618","article-title":"Chronic Kidney Disease Elicits an Intestinal Inflammation Resulting in Intestinal Dysmotility Associated with the Activation of Inducible Nitric Oxide Synthesis in Rat","volume":"97","author":"Yu","year":"2018","journal-title":"Digestion"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/MOG.0000000000000481","article-title":"On cell death in the intestinal epithelium and its impact on gut homeostasis","volume":"34","author":"Blander","year":"2018","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41419-018-1275-5","article-title":"Elevated apoptosis impairs epithelial cell turnover and shortens villi in TNF-driven intestinal inflammation","volume":"10","author":"Parker","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"655","DOI":"10.5009\/gnl16496","article-title":"Heme oxygenase-1 induction and anti-inflammatory actions of Atractylodes macrocephala and Taraxacum herba extracts prevented colitis and was more effective than sulfasalazine in preventing relapse","volume":"11","author":"Han","year":"2017","journal-title":"Gut Liv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.3109\/10715762.2012.732698","article-title":"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","volume":"46","author":"Yasukawa","year":"2012","journal-title":"Free Radic. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10157-018-1641-8","article-title":"Clinical epidemiology of infectious disease among patients with chronic kidney disease","volume":"23","author":"Ishigami","year":"2019","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10208","article-title":"Intestinal homeostasis and its breakdown in inflammatory bowel disease","volume":"474","author":"Maloy","year":"2011","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1159\/000299798","article-title":"Indoxyl sulfate upregulates expression of ICAM-1 and MCP-1 by oxidative stress-induced NF-kappaB activation","volume":"31","author":"Tumur","year":"2010","journal-title":"Am. J. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bolati, D., Shimizu, H., Yisireyili, M., Nishijima, F., and Niwa, T. (2013). Indoxyl sulfate, a uremic toxin, downregulates renal expression of Nrf2 through activation of NF-\u03baB. BMC Nephrol., 14.","DOI":"10.1186\/1471-2369-14-56"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"F662","DOI":"10.1152\/ajprenal.00421.2009","article-title":"Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure","volume":"298","author":"Kim","year":"2010","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.taap.2018.09.030","article-title":"Nrf2 activator for the treatment of kidney diseases","volume":"360","author":"Yamawaki","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lin, Y.T., Wu, P.H., Tsai, Y.C., Hsu, Y.L., Wang, H.Y., Kuo, M.C., Kuo, P.L., and Hwang, S.J. (2019). Indoxyl Sulfate Induces Apoptosis Through Oxidative Stress and Mitogen-Activated Protein Kinase Signaling Pathway Inhibition in Human Astrocytes. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020191"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"H\u00e9naut, L., Mary, A., Chillon, J.M., Kamel, S., and Massy, Z.A. (2018). The Impact of Uremic Toxins on Vascular Smooth Muscle Cell Function. Toxins, 10.","DOI":"10.3390\/toxins10060218"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1093\/ndt\/17.11.1964","article-title":"IL-1beta, TNF-alpha and IL-6 release from monocytes in haemodialysis patients in relation to dialytic age","volume":"17","author":"Malaponte","year":"2002","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1523-1755.2005.00200.x","article-title":"IL-10, IL-6, and TNF-alpha: Central factors in the altered cytokine network of uremia--the good, the bad, and the ugly","volume":"67","author":"Stenvinkel","year":"2005","journal-title":"Kidney Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and Pathologic Concentrations of Uremic Toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"31","DOI":"10.5527\/wjn.v2.i2.31","article-title":"Inflammatory status in chronic renal failure: The role of homocysteinemia and pro-inflammatory cytokines","volume":"2","author":"Tbahriti","year":"2013","journal-title":"World J. Nephrol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1007\/s00216-011-5436-y","article-title":"Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography-tandem mass spectrometry","volume":"401","author":"Zhu","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_62","first-page":"4557","article-title":"A guide to histomorphological evaluation of intestinal inflammation in mouse models","volume":"7","author":"Erben","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1177\/0023677218815718","article-title":"Characterization of inflammatory infiltrate of ulcerative dermatitis in C57BL\/6NCrl-Tg(HMGA1P6)1Pg mice","volume":"53","author":"Esposito","year":"2019","journal-title":"Lab. Anim."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13893","DOI":"10.1096\/fj.201901230RR","article-title":"Prep1 regulates angiogenesis through a PGC-1\u03b1\u2013mediated mechanism","volume":"33","author":"Cimmino","year":"2019","journal-title":"FASEB J."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Raehtz, K.D., Barrenas, F., Xu, C., Busman-Sahay, K., Valentine, A., Law, L., Ma, D., Policicchio, B.B., Wijewardana, V., and Brocca-Cofano, E. (2020). African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal barrier integrity. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008333"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-15885-6","article-title":"Andy\u2019s Algorithms: New automated digital image analysis pipelines for FIJI","volume":"7","author":"Law","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Rapa, S.F., Di Paola, R., Cordaro, M., Siracusa, R., D\u2019Amico, R., Fusco, R., Autore, G., Cuzzocrea, S., Stuppner, H., and Marzocco, S. (2021). Plumericin Protects against Experimental Inflammatory Bowel Disease by Restoring Intestinal Barrier Function and Reducing Apoptosis. Biomedicines, 12.","DOI":"10.3390\/biomedicines9010067"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Adesso, S., Russo, R., Quaroni, A., Autore, G., and Marzocco, S. (2018). Astragalus membranaceus Extract Attenuates Inflammation and Oxidative Stress in Intestinal Epithelial Cells via NF-\u03baB Activation and Nrf2 Response. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030800"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1096\/fj.201902040R","article-title":"Plumericin prevents intestinal inflammation and oxidative stress in vitro and in vivo","volume":"34","author":"Rapa","year":"2020","journal-title":"FASEB J."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Pepe, G., Rapa, S.F., Salviati, E., Bertamino, A., Auriemma, G., Cascioferro, S., Autore, G., Quaroni, A., Campiglia, P., and Marzocco, S. (2020). Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells. Antioxidants, 9.","DOI":"10.3390\/antiox9080699"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Basilicata, M.G., Pepe, G., Rapa, S.F., Merciai, F., Ostacolo, C., Manfra, M., Di Sarno, V., Autore, G., De Vita, D., and Marzocco, S. (2019). Anti-Inflammatory and Antioxidant Properties of Dehydrated Potato-Derived Bioactive Compounds in Intestinal Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20236087"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1135\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:14:49Z","timestamp":1760159689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,24]]},"references-count":71,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22031135"],"URL":"https:\/\/doi.org\/10.3390\/ijms22031135","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,24]]}}}