Abstract
Gastrointestinal symptoms are the first signs of fluoride (F) toxicity. In the present study, the jejunum of rats chronically exposed to F was evaluated by proteomics, as well as by morphological analysis. Wistar rats received water containing 0, 10 or 50 mgF/L during 30 days. HuC/D, neuronal Nitric Oxide (nNOS), Vasoactive Intestinal Peptide (VIP), Calcitonin Gene Related Peptide (CGRP), and Substance P (SP) were detected in the myenteric plexus of the jejunum by immunofluorescence. The density of nNOS-IR neurons was significantly decreased (compared to both control and 10 mgF/L groups), while the VIP-IR varicosities were significantly increased (compared to control) in the group treated with the highest F concentration. Significant morphological changes were seen observed in the density of HUC/D-IR neurons and in the area of SP-IR varicosities for F-treated groups compared to control. Changes in the abundance of various proteins correlated with relevant biological processes, such as protein synthesis, glucose homeostasis and energy metabolism were revealed by proteomics.
Highlights
Gastrointestinal symptoms are the first signs of fluoride (F) toxicity
The group treated with 50 mgF/L had a significant decrease in the density of nNOS-IR neurons
Important morphological changes were seen in HUC/D-IR and nNOS-IR neurons, as well as in Vasoactive Intestinal Peptide (VIP)-IR, Calcitonin Gene Related Peptide (CGRP)-IR, and Substance P (SP)-IR varicosities for the groups treated with both 10 and 50 mgF/L
Summary
Gastrointestinal symptoms are the first signs of fluoride (F) toxicity. In the present study, the jejunum of rats chronically exposed to F was evaluated by proteomics, as well as by morphological analysis. Immunofluorescence techniques revealed important alterations in the morphology of different types of enteric neurons and proteomic analysis demonstrated changes in the expression of several proteins of the duodenum of rats[13] after chronic exposure to F, providing the first insights for the comprehension of the mechanisms underlying the actions of F on the bowel. Considering that each segment of the small intestine has distinct anatomical, histological and physiological characteristics with functional implications[14], this study evaluated the morphology of distinct subtypes of enteric neurons of the jejunum after chronic exposure to F. Quantitative label-free proteomics tools were employed to evaluate the changes on the pattern of protein profile of the jejunum, after exposure to F, in attempt to provide mechanistic explanations for the effects of this ion in the intestine
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