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Metabolic differences in the kynurenine pathway (KP) of tryptophan (TRP) degradation are observed in both MS and a CPZ mouse model. Our goal was to analyze the kynurenine, serotonin, and indole pathways of TRP degradation on the periphery, in the neurodegenerative processes of inflammation. In our study, mice were fed with 0.2% CPZ toxin for 5 weeks. We examined the metabolites in the three pathways of TRP breakdown in urine, plasma, and relevant visceral organs with bioanalytical measurements. In our analyses, we found a significant increase in plasma TRP, 5-hydroxytryptophan (5-HTP), and indole-3-acetic acid (IAA) levels, while a decrease in the concentrations of 3-hydroxy-L-kynurenine (3-HK), xanthurenic acid (XA), kynurenic acid (KYNA), and quinaldic acid in the plasma of toxin-treated group was found. A marked decrease in the levels of 3-HK, XA, KYNA, quinaldic acid, and indole-3-lactic acid was also observed in the visceral organs by the end of the poisoning. Furthermore, we noticed a decrease in the urinary levels of the TRP, KYNA, and XA metabolites, while an increase in serotonin and 5-hydroxyindoleacetic acid in the CPZ group was noticed. The toxin treatment resulted in elevated tryptamine and indoxyl sulfate levels and reduced IAA concentration. Moreover, the urinary para-cresyl sulfate concentration also increased in the treated group. In the present study, we showed the differences in the three main metabolic pathways of TRP degradation in the CPZ model. We confirmed the relationship and correlation between the content of the kynurenine metabolites in the plasma and the tissues of the visceral organs. We emphasized the suppression of the KP and the activity of the serotonin and indole pathways with a particular regard to the involvement of the microbiome by the indole pathway. Consequently, this is the first study to analyze in detail the distribution of the kynurenine, serotonin, and indole pathways of TRP degradation in the periphery.<\/jats:p>","DOI":"10.3390\/ijms26030976","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T04:32:22Z","timestamp":1737693142000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Plasma and Visceral Organ Kynurenine Metabolites Correlate in the Multiple Sclerosis Cuprizone Animal Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3230-6261","authenticated-orcid":false,"given":"Helga","family":"Poly\u00e1k","sequence":"first","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"},{"name":"Preventive Health Sciences Research Group, Incubation Competence Centre of the Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-1212","authenticated-orcid":false,"given":"Zsolt","family":"Galla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Albert Szent-Gy\u00f6rgyi Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0252-4778","authenticated-orcid":false,"given":"Cecilia","family":"Rajda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3591-6054","authenticated-orcid":false,"given":"P\u00e9ter","family":"Monostori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Albert Szent-Gy\u00f6rgyi Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5389-3266","authenticated-orcid":false,"given":"P\u00e9ter","family":"Kliv\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"},{"name":"HUN-REN-SZTE Neuroscience Research Group, Danube Neuroscience Research Laboratory, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"},{"name":"HUN-REN-SZTE Neuroscience Research Group, Danube Neuroscience Research Laboratory, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1021\/acschemneuro.0c00695","article-title":"Gut Microbiota Changes in Experimental Autoimmune Encephalomyelitis and Cuprizone Mice Models","volume":"12","author":"Moles","year":"2021","journal-title":"ACS Chem. 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