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The Involvement of Mast Cells in the Irinotecan-Induced Enteric Neurons Loss and Reactive Gliosis

The Involvement of Mast Cells in the Irinotecan-Induced Enteric Neurons Loss and Reactive Gliosis

Ludmila T Nogueira, Deiziane V S Costa, Antoniella S Gomes, Conceição S Martins, Angeline M H P Silva, Juliana M Coelho-Aguiar, Patrícia Castelucci, Roberto C P Lima-Júnior, Renata F C Leitão, Vivaldo Moura-Neto, etc.

J Neuroinflammation. 2017 Apr 7;14(1):79.

PMID: 28388962

Abstract:

Background:
The irinotecan (CPT-11) causes intestinal mucositis and diarrhea that may be related to changes in the enteric nervous system (ENS). In inflammatory condition, mast cells release a variety of pro-inflammatory mediators that can interact with the ENS cells. It has not been explored whether CPT-11 is able to alter the enteric glial and neuronal cell, and the role of mast cells in this effect. Therefore, this study was conducted to investigate the effect of CPT-11 on the enteric glial and neuronal cells, as well as to study the role of mast cells in the CPT-11-induced intestinal mucositis.
Methods:
Intestinal mucositis was induced in Swiss mice by the injection of CPT-11 (60 mg/kg, i.p.) once a day for 4 days following by euthanasia on the fifth day. To investigate the role of mast cells, the mice were pretreated with compound 48/80 for 4 days (first day, 0.6 mg/kg; second day, 1.0 mg/kg; third day, 1.2 mg/kg; fourth day, 2.4 mg/kg) to induce mast cell degranulation before the CPT-11 treatment.
Results:
Here, we show that CPT-11 increased glial fibrillary acidic protein (GFAP) and S100β gene and S100β protein expressions and decreased HuC/D protein expression in the small intestine segments. Concomitantly, CPT-11 enhanced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and inducible nitric oxide synthase (iNOS) gene expression, associated with an increase in the total number macrophages (positive cells for ionized calcium-binding adapter molecule, Iba-1) and degranulated mast cells in the small intestine segments and caused significant weight loss. The pretreatment with compound 48/80, an inductor of mast cells degranulation, significantly prevented these CPT-11-induced effects.
Conclusions:
Our data suggests the participation of mast cells on the CPT-11-induced intestinal mucositis, macrophages activation, enteric reactive gliosis, and neuron loss.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
CS31041944	Irinotecan Related Compound D			Price

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