Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 77, Issue 2, Pages 323-332Publisher
SPRINGER
DOI: 10.1007/s00280-015-2938-x
Keywords
Irinotecan; 5-Fluorouracil; Mucositis; Intestine; Inflammation
Categories
Funding
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [308879/2009-0, 307143/2014-7]
- FUNCAP (Fundacao Cearense de Apoio ao Desenvolvimento Cientifico) [11.01.00/08]
- CNPq
Ask authors/readers for more resources
Intestinal mucositis (IM) is a common side effect of anticancer agents. Despite polychemotherapy use in clinical practice, the pathogenesis of IM has been investigated in single drug injection animal models. However, the progression of IM could vary according to drug regimens. Thus, we aimed to develop a new experimental mucositis model induced by combining irinotecan and 5-fluorouracil (5-FU) treatments. IM was induced in male C57BL/6 mice by the intraperitoneal administration of either 0.9 % saline (5 mL/kg), irinotecan (IRI, 30 or 45 mg/kg), 5-FU (25, 37.5, or 50 mg/kg), or the combination of these doses (IRI + 5-FU) for 4 days. Animal survival, body mass variation, and diarrhea scores were evaluated daily. On the 7th day, the mice were euthanized, and intestinal samples were collected for histopathology and morphometric analysis, as well as for the determination of myeloperoxidase activity and cytokine dosage (TNF-alpha and IL-6). The optimal dose combination that induced IM and presented no substantial mortality on the 7th day was IRI (45 mg/kg) + 5-FU (37.5 mg/kg), which was used for subsequent studies. IRI and 5-FU in combination induced significant diarrhea, body weight loss, intestinal damage, inflammatory cell infiltration, and increased levels of cytokines when compared with other groups (P < 0.05). Neither IRI nor 5-FU alone induced IM. We developed a new experimental model of IM induced by combining irinotecan and 5-FU treatments, which will allow us to gain a better knowledge concerning the pathogenesis of this disease through the pharmacological modulation of key inflammatory mediators.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available