Does Rheumatoid Arthritis Affects the Nitrergic Density and Somatic Area of the nNOS-Immunoreactive (IR) Myenteric Neurons, as well as the Morphometric Areas of CGRP and VIP-IR Varicosities of the Ileum of Arthritic Rats?

Ahmed S Ashour,Virginia K

doi:10.35248/2165-8048.19.9.311

Abstract

Few studies regarding arthritic diseases have been performed to verify the presence of the neurodegeneration. Given the increased oxidative stress and extra-articular effects of the rheumatoid arthritis, the gastrointestinal studies should be further investigated aiming a better understanding of the systemic effects the disease on enteric nervous system. To determine whether the rheumatoid arthritis affects the nitrergic density and somatic area of the nNOSimmunoreactive (IR) myenteric neurons, as well as the morphometric areas of CGRP and VIP-IR varicosities of the ileum of arthritic rats. Twenty 58-day-old male Holtzmann rats were distributed in two groups: control and arthritic. The arthritic group received a single injection of the Freund’s Complete Adjuvant in order to induce arthritis model. The whole-mount preparations of ileum were processed for immunohistochemistry to VIP, CGRP and nNOS. Quantification was used for the nitrergic neurons and morphometric analyses were performed for the three markers. The arthritic disease induced a reduction 6% in ileal area compared to control group. No significant differences were observed in nitrergic density comparing both groups. However, arthritic group yielded a reduction of the nitrergic neuronal somatic area and VIP-IR varicosity areas. However, an increase of varicosity CGRP-IR areas was also observed. Despite arthritis resulted in no alterations in the number of nitrergic neurons, the retraction of ileal area and reduction of nitrergic somatic and VIP-IR varicosity areas may suggest a negative impact the disease on the ENS.

Highlights

Rheumatoid arthritis (RA) is a progressive, chronic inflammatory, autoimmune and multi-systemic disease that affects several tissues, but mainly the joints, and reaches approximately 1% of the world’s population
The inflammatory process of RA is mediated by cytokines (e.g. IL-1, TNF-α, IL-1, IL-6, IL-17, etc) and reactive oxygen species (ROS) that modulates the activity of inflammatory cells [3,4,5,6,7,8,9,10]
Given that poor correlation between the extra-articular effects of RA on Enteric Nervous System (ENS) and susceptibility of enteric neurons to the RAinduced oxidative stress, the aim of this study was to investigate whether the RA affects the ENS evaluating quantitative and morphometric parameters of vasoactive intestinal polypeptide (VIP) and neuronal nitric oxide synthase and calcitonin gene-related peptide (CGRP)

Summary

Introduction

Rheumatoid arthritis (RA) is a progressive, chronic inflammatory, autoimmune and multi-systemic disease that affects several tissues, but mainly the joints, and reaches approximately 1% of the world’s population. The RA is characterized by the infiltration and activation of inflammatory cells in the tissues and fluids of the synovial joints [1,2,3,4]. Pro-inflammatory mediators promote and perpetuate chronic immune-mediated inflammation of soft tissue, resulting in joint destruction [2,5,6,7,8]. The inflammatory process of RA is mediated by cytokines (e.g. IL-1, TNF-α, IL-1, IL-6, IL-17, etc) and reactive oxygen species (ROS) that modulates the activity of inflammatory cells [3,4,5,6,7,8,9,10]. The ROS is produced by activated phagocytes, with a protective function against pathogenic invaders, these cells can promote tissue through intensifying the inflammation process. The synthesis ROS occurs due to the cycles of Received: September 14, 2019; Accepted: September 27, 2019; Published: October 07, 2019

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