Antioxidant Effects of the Quercetin in the Jejunal Myenteric Innervation of Diabetic Rats

Abstract

PurposeEnteric glial cells (EGCs) exert a critical role in the structural integrity, defense, and metabolic function of enteric neurons. Diabetes mellitus is a chronic disease characterized by metabolic disorders and chronic autonomic neuropathy. Quercetin supplementation, which is a potent antioxidant, has been used in order to reduce the effects of diabetes-induced oxidative stress. The purpose of this research was to investigate the effects of quercetin supplementation in the drinking water at a daily dose of 40 mg on the glial cells and neurons in the jejunum of diabetic rats.Materials and methodsTwenty 90-day-old male adult Wistar rats were split into four groups: normoglycemic control (C), normoglycemic control supplemented with quercetin (Q), diabetic (D), and diabetic supplemented with quercetin (DQ). After 120 days, the jejunums were collected, and immunohistochemical technique was performed to label S-100-immunoreactive glial cells and HuC/D-immunoreactive neurons.ResultsAn intense neuronal and glial reduction was observed in the jejunum of diabetic rats. Quercetin displayed neuroprotective effects due to reduced cell body areas of neurons and glial cells in Q and DQ groups compared to their controls (C and D groups). Interestingly, quercetin prevented the glial and neuronal loss with a higher density for the HuC/D-immunoreactive neurons (23.06%) and for the S100-immunoreactive glial cells (14.55%) in DQ group compared to D group.ConclusionQuercetin supplementation promoted neuroprotective effects through the reduction of neuronal and glial body areas and a slight prevention of neuronal and glial density reduction.

Enteric glial cell activation protects enteric neurons from damage due to diabetes in part via the promotion of neurotrophic factor release

“…Correspondingly, the change in c‐fos, an indicator of activated EGCs, was also consistent with that found in EGCs. These findings contrast with those noting injury of EGCs during diabetic disease pathology; this difference is likely due to the involvement of different tissue segments and the nerve plexus used in experiments, as reports have demonstrated that there are variations in the effect of diabetes in different regions and plexus of the GI tract . However, several studies have provided evidence in favor of our results.…”

“…Although ENS damage in diabetic animals has been reported in several studies, our results did not show significant changes in PGP9.5‐immunopositive cells in the ilea of rats 1, 4, 8, or 16 weeks after the induction of diabetes. Similar to our results, a previous study demonstrated that a longer period, up to 19 weeks, is necessary to cause total loss of neurons in the ilea of diabetic rats .…”

Does the Rheumatoid Arthritis Affect the Enteric Nervous System?

“…Furthermore, CGRP has antioxidant and anti-inflammatory effects (22,33,34) . In this study, the reduction of VIP-IR varicosity areas may indicate the presence of inflammatory process in the ileum induced by the AR, which may lead to a decrease of production and release of this neuropetide (24,30) . Furthermore, NO induces the release of VIP in the myenteric plexus (35,36) , and both morphometric reductions may indicate correlations with decrease in the production of the neuronal NO and VIP.…”

“…In the ENS, neuronal NOS-derived NO acts as neurotransmitter, which mediates the relaxing components of bowel peristalsis (29) . These phenotypic changes may indicate a compensatory mechanism to either GI dysfunctions or neurons loss in order to balance its bowel activity closer to ideal (30) . However, in our study, the reduction of somatic area of the nNOS-IR myenteric neurons suggests a negative effect induced by the AR since no alterations were observed in the nitrergic density.…”

“…The hypertrophy of the neuronal size is commonly associated with an increased enzymatic synthesis as a compensatory mechanism against the neuronal density loss, whereas the neuronal atrophy may indicate negative effects by the reduction of production of the neurotransmitter and oxidative injury induced by the disease on the ENS, resulting in a decrease of gastrointestinal function (28,30) . In our study, no nitrergic changes were observed but associated with reduction of the neuronal body area of the nNOS-IR neurons, which may also suggest an arthritis-induced harmful effect.…”