Original Article
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World J Gastroenterol. Oct 14, 2013; 19(38): 6416-6426
Published online Oct 14, 2013. doi: 10.3748/wjg.v19.i38.6416
Diabetic neuropathy: An evaluation of the use of quercetin in the cecum of rats
Paulo Emilio Botura Ferreira, Cláudia Regina Pinheiro Lopes, Angela Maria Pereira Alves, Éder Paulo Belato Alves, David Robert Linden, Jacqueline Nelisis Zanoni, Nilza Cristina Buttow
Paulo Emilio Botura Ferreira, Cláudia Regina Pinheiro Lopes, Angela Maria Pereira Alves, Éder Paulo Belato Alves, Jacqueline Nelisis Zanoni, Nilza Cristina Buttow, Department of Morphological Sciences, Universidade Estadual de Maringá, Maringá, PR. CEP 87020-900, Brazil
David Robert Linden, Department of Physiology and Biomedical Engineering and Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
Author contributions: Ferreira PEB collected data and wrote the paper; Lopes CRP collected data; Alves AMP, Alves EPB and Buttow NC designed the study and edited the manuscript; Linden DR critically analyzed the paper; Zanoni JN analyzed the data.
Supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES, Brasil; NIH grant, No. DK76665
Correspondence to: Nilza Cristina Buttow, PhD, Department of Morphological Sciences, Universidade Estadual de Maringá, Av. Colombo, 5790 Bloco H-79, Maringá, PR. CEP 87020-900, Brazil. ncbuttow@gmail.com
Telephone: +55-44-30114705 Fax: +55-44-30114340
Received: February 15, 2013
Revised: May 20, 2013
Accepted: June 19, 2013
Published online: October 14, 2013
Processing time: 231 Days and 21.8 Hours
Abstract

AIM: To investigate the effect of quercetin supplementation on the myenteric neurons and glia in the cecum of diabetic rats.

METHODS: Total preparations of the muscular tunic were prepared from the ceca of twenty-four rats divided into the following groups: control (C), control supplemented with quercetin (200 mg/kg quercetin body weight) (CQ), diabetic (D) and diabetic supplemented with quercetin (DQ). Immunohistochemical double staining technique was performed with HuC/D (general population)/nitric oxide synthase (nNOS), HuC-D/S-100 and VIP. Density analysis of the general neuronal population HuC/D-IR, the nNOS-IR (nitrergic subpopulation) and the enteric glial cells (S-100) was performed, and the morphometry and the reduction in varicosity population (VIP-IR) in these populations were analyzed.

RESULTS: Diabetes promoted a significant reduction (25%) in the neuronal density of the HuC/D-IR (general population) and the nNOS-IR (nitrergic subpopulation) compared with the C group. Diabetes also significantly increased the areas of neurons, glial cells and VIP-IR varicosities. Supplementation with quercetin in the DQ group prevented neuronal loss in the general population and increased its area (P < 0.001) and the area of nitrergic subpopulation (P < 0.001), when compared to C group. Quercetin induced a VIP-IR and glial cells areas (P < 0.001) in DQ group when compared to C, CQ and D groups.

CONCLUSION: In diabetes, quercetin exhibited a neuroprotective effect by maintaining the density of the general neuronal population but did not affect the density of the nNOS subpopulation.

Keywords: Diabetes; Myenteric plexus; Neuroprotection; Neuronal nitric oxide synthase; Vasoactive intestinal polypeptide; Enteric glia

Core tip: The present study is the first to report a neuroprotective effect of the flavonoid quercetin in the general population of enteric neurons in the cecum of rats with experimental diabetes mellitus. Quercetin did not reduce the loss of nitrergic neurons in the diabetic rats. This observation suggests that selective changes in the neurochemical code of enteric neurons occur in the presence of quercetin. We propose a causal link between the area and number of glial cells and the size of VIP-IR (reduction in varicosity population) varicosities. Although this link is not fully understood, these observations provide a basis for further studies to clarify the link between glia and VIP-IR varicosities.