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UK Against Fluoridation

Saturday, February 17, 2018

Chronic treatment with fluoride affects the jejunum: insights from proteomics and enteric innervation analysis

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. Wistarrats 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........

In conclusion, chronic exposure to F, especially to the highest concentration evaluated, increased the thickness of the tunica muscularis and altered the pattern of protein expression. Extensive downregulation of several isoforms of histones might have contributed to the alterations found in the morphology of enteric neurons in response to F exposure. Additionally, changes in proteins involved in energy metabolism indicate a shift from aerobic to anaerobic metabolism upon exposure to the highest F concentration. These findings provide new insights into the mechanisms involved in F toxicity in the intestine.




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