Effects of Chronic Fluoride Exposure on the Jejunum of Rats

Objectives: The gastrointestinal tract (GIT) is the main route of exposure to fluoride (F) and gastrointestinal symptoms are the first signs of F toxicity. In the present study we evaluated the effects of chronic F exposure on the jejunum of rats using morphological and proteomic analyses.
Methods: Male Wistar rats received water containing 0, 10 or 50 mgF/L for 30 days. These F concentrations correspond to ~2 and 10 mg/L in the drinking water for humans. Immunofluorescence techniques were performed in the myenteric plexus of the jejunum to detect HuC/D, neuronal Nitric Oxide (nNOS), Vasoactive Intestinal Peptide (VIP), Calcitonin Gene Related Peptide (CGRP), and Substance P (SP). Proteomic analysis of jejunum was performed using nanoAcquity UPLC-Xevo QTof MS system and the ProteinLynx Global Server (PLGS) software. For bioinformatics analysis, the Cytoscape software and the Cluster Marker and Cluego pluggins were used.
Results: The 50 mgF/L group presented a significant decrease in the density of nNOS-IR neurons (compared to both control and 10 mgF/L groups) and a significant increase in the VIP-IR varicosities (compared to control). Significant morphological alterations were also observed in the density of HUC/D-IR neurons and in the area of SP-IR varicosities for both groups (10 and 50 mgF/L) compared to control. Proteomic analysis of the jejunum demonstrated alterations in the abundance of several proteins correlated with important biological processes, such as protein synthesis, glucose homeostasis and energy metabolism.
Conclusions: These findings provide new insights into the mechanisms involved in F toxicity in the intestin.