ArticleSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer2019
Amitriptyline prevents CPT-11-induced early-onset diarrhea and colonic apoptosis without reducing overall gastrointestinal damage in a rat model of mucositis.
Article in Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 11 citations in OpenAlex.
- Huangqi Baihe Granules alleviate chemotherapy-induced intestinal mucositis in Drosophila and mice.AMB Express · 2026Article
- Restore intestinal steady-state: new advances in the clinical management of chemotherapy-associated diarrhea and constipation.Journal of molecular histology · 2025Review
- Banxia Xiexin decoction combined with 5-ASA protects against CPT-11-induced intestinal dysfunction in rats via inhibiting TLR4/NF-κB signaling pathway.Immunity, inflammation and disease · 2024Article
- Structural insight and analysis of TLR4 interactions with IAXO-102, TAK-242 and SN-38: an in silico approach.In silico pharmacology · 2023Article
- Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models.International journal of molecular sciences · 2022Article
- Investigation of the Possible Protective Effect ofAntioxidants (Basel, Switzerland) · 2022Article
- Effects of a novel toll-like receptor 4 antagonist IAXO-102 in a murine model of chemotherapy-induced gastrointestinal toxicity.Cancer chemotherapy and pharmacology · 2022Article
- Chemotherapy-Induced Intestinal Microbiota Dysbiosis Impairs Mucosal Homeostasis by Modulating Toll-like Receptor Signaling Pathways.International journal of molecular sciences · 2021Review
- NIR triggered PLGA coated Au-TiODrug delivery · 2020Article
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5 authors at 2 institutions in 1 country.
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Abstract
purposeGastrointestinal mucositis (GIM) is one of the most debilitating side effects of the chemotherapy agent, irinotecan hydrochloride (CPT-11). The toll-like receptor (TLR) pathway is a key mediator implicated in the pathophysiology underlying GIM. The tricyclic antidepressant amitriptyline has been shown to inhibit TLR2 and TLR4 activity in in vitro models. The aim of this study was therefore to investigate the effect of amitriptyline on the development of GIM following CPT-11.
methodsMale albino Wistar rats were treated with either CPT-11 (125 mg/kg, i.p., n = 18), amitriptyline (20 mg/kg, n = 18), both agents (n = 18), or vehicle control (n = 18) and killed at 6, 48, or 96 h. Differences between groups in measurements of gastrointestinal toxicity (diarrhea and weight loss), mucosal injury (apoptosis and histopathology score), colonic expression of TLRs, and pro-inflammatory cytokines were determined.
resultsCPT-11-induced diarrhea and colonic apoptosis were inhibited by amitriptyline at 6 h. However, rats were not protected from weight loss or mucosal injury over the time course of CPT-11-induced GIM. Interleukin-1 beta transcript expression was significantly decreased with amitriptyline treatment at 6 h, although protein expression did not differ between groups. There was no change in TLR4 or TLR2 expression in any group.
conclusionsProphylactic amitriptyline was able to inhibit early intestinal damage in this rat model of CPT-11-induced GIM, but exacerbated late-onset injury. These findings do not support use of amitriptyline as an approach for mitigation of GIM in this setting.
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