Indoximod Attenuates Inflammatory Responses in Acetic Acid-Induced Acute Colitis by Modulating Toll-like Receptor 4 (TLR4) Signaling and Proinflammatory Cytokines in Rats
<i>Background and Objectives:</i> Acute ulcerative colitis is characterized by excessive mucosal inflammation and epithelial disruption, often driven by dysregulated cytokine and immune signaling. Indoximod (1-methyl-DL-tryptophan), although not a direct enzymatic inhibitor, modulates th...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Medicina |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1648-9144/61/6/1033 |
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| Summary: | <i>Background and Objectives:</i> Acute ulcerative colitis is characterized by excessive mucosal inflammation and epithelial disruption, often driven by dysregulated cytokine and immune signaling. Indoximod (1-methyl-DL-tryptophan), although not a direct enzymatic inhibitor, modulates the indoleamine 2,3-dioxygenase (IDO) pathway and has been reported to exert immunoregulatory effects in various models of inflammation. This study aimed to evaluate the protective effects of Indoximod in an acetic acid-induced colitis model in rats, focusing on histopathological changes and inflammatory mediators. <i>Materials and Methods:</i> Thirty male Wistar albino rats were randomly assigned to three groups (n = 10 per group): <i>Group 1 (Control)</i> received 0.9% saline oral gavage; <i>Group 2</i> <i>(Colitis)</i> received intrarectal 4% acetic acid to induce colitis and were then treated with saline; <i>Group 3 (Colitis + Indoximod)</i> received 4% acetic acid followed by oral gavage administration of Indoximod (30 mg/kg) for 15 consecutive days. Histopathological evaluation of colonic tissues was performed using hematoxylin and eosin (H&E) staining. Colonic expression of Toll-like receptor 4 (TLR4) and plasma levels of tumor necrosis factor-alpha (TNF-α), pentraxin-3 (PTX-3), and platelet-activating factor (PAF) were quantified using enzyme-linked immunosorbent assay (ELISA). <i>Results:</i> Acetic acid-induced colitis significantly increased mucosal damage, TLR4 expression, and circulating levels of TNF-α, PTX-3, and PAF compared with controls (<i>p</i> < 0.001). Indoximod treatment markedly reduced histological injury and significantly suppressed TLR4 and TNF-α levels (<i>p</i> < 0.01), along with partial reductions in PTX-3 (<i>p</i> < 0.05). However, PAF levels remained elevated despite treatment, indicating limited efficacy in PAF-associated pathways. <i>Conclusions:</i> Indoximod exhibited anti-inflammatory effects in this acute colitis model, likely by downregulating key proinflammatory mediators. |
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| ISSN: | 1010-660X 1648-9144 |