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Open AccessArticle

Pro-Inflammatory Effects of Indoxyl Sulfate in Mice: Impairment of Intestinal Homeostasis and Immune Response

1
Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy
2
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Napoli, NA, Italy
3
UOC Nephrology AORN “San Giuseppe Moscati”, C.da Amoretta, 83100 Avellino, AV, Italy
4
Department of Medicine and Surgery, University of Salerno, 84084 Fisciano, SA, Italy
5
Pharmaceuticals Division, Kureha Corporation, Tokyo 169-8503, Japan
*
Author to whom correspondence should be addressed.
These authors equally contributed as second author.
Academic Editor: G. Jean Harry
Int. J. Mol. Sci. 2021, 22(3), 1135; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031135
Received: 11 January 2021 / Revised: 20 January 2021 / Accepted: 22 January 2021 / Published: 24 January 2021
(This article belongs to the Special Issue Bioactive and Uremic Toxins in Chronic Kidney Disease 2.0)
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 (125–1000 µM) increased tumor necrosis factor-α 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. View Full-Text
Keywords: indoxyl sulfate; chronic kidney disease; intestinal inflammation; oxidative stress; intestinal epithelial cells; primary murine peritoneal macrophages indoxyl sulfate; chronic kidney disease; intestinal inflammation; oxidative stress; intestinal epithelial cells; primary murine peritoneal macrophages
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MDPI and ACS Style

Rapa, S.F.; Prisco, F.; Popolo, A.; Iovane, V.; Autore, G.; Di Iorio, B.R.; Dal Piaz, F.; Paciello, O.; Nishijima, F.; Marzocco, S. Pro-Inflammatory Effects of Indoxyl Sulfate in Mice: Impairment of Intestinal Homeostasis and Immune Response. Int. J. Mol. Sci. 2021, 22, 1135. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031135

AMA Style

Rapa SF, Prisco F, Popolo A, Iovane V, Autore G, Di Iorio BR, Dal Piaz F, Paciello O, Nishijima F, Marzocco S. Pro-Inflammatory Effects of Indoxyl Sulfate in Mice: Impairment of Intestinal Homeostasis and Immune Response. International Journal of Molecular Sciences. 2021; 22(3):1135. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031135

Chicago/Turabian Style

Rapa, Shara F.; Prisco, Francesco; Popolo, Ada; Iovane, Valentina; Autore, Giuseppina; Di Iorio, Biagio R.; Dal Piaz, Fabrizio; Paciello, Orlando; Nishijima, Fuyu; Marzocco, Stefania. 2021. "Pro-Inflammatory Effects of Indoxyl Sulfate in Mice: Impairment of Intestinal Homeostasis and Immune Response" Int. J. Mol. Sci. 22, no. 3: 1135. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031135

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