PMID- 31622607 OWN - NLM STAT- MEDLINE DCOM- 20191217 LR - 20191217 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 238 DP - 2019 Dec 1 TI - Rheumatoid arthritis induces enteric neurodegeneration and jejunal inflammation, and quercetin promotes neuroprotective and anti-inflammatory actions. PG - 116956 LID - S0024-3205(19)30883-5 [pii] LID - 10.1016/j.lfs.2019.116956 [doi] AB - AIMS: The aim of our study was to study the pathological mechanisms induced by the rheumatoid arthritis (RA) on the Enteric Nervous System (ENS). MAIN METHODS: We evaluated the effect of the chronic arthritis and its treatment with 50 mg/kg quercetin alone (AQ) and combined with 17.5 mg/kg ibuprofen (AIQ) for 60 days on neurons, glial cells and intestinal wall. Other groups were used: control (C), arthritic (A) and arthritic treated with 17.5 mg/kg ibuprofen (AI). After 60 days, the jejunum was removed and processed for immunohistochemical techniques. Immunostainings were performed for HuC/D and S100 (myenteric and submucosal plexuses), and GFAP (only myenteric plexus), while immunolabeling for CD45 and CD20 lymphocytes was performed using cryosections. Western blot was performed for GDNF, S100 and GFAP. KEY FINDINGS: A group yielded a remarkable density decrease of the neurons and glial cells with morphometric changes in the myenteric and submucosal plexuses, reduction of the GDNF expression and GFAP-related parameters (GFAP expression, occupancy area and GFAP-expressing glial cells) and intestinal inflammation and atrophy of the mucosa and intestinal wall. AQ group substantially reversed most of these effects, except for intestinal atrophy of the jejunum. The AI and AIQ groups displayed lower beneficial results than AQ for parameters related to the neurons and glial cells, although AIQ did not prevent the inflammation of the mucosa. SIGNIFICANCE: The severe chronic rheumatoid arthritis induced severe effects on ENS and mucosa, and quercetin treatment continues to be an important antioxidant supplement preventing the progression of the RA severity. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Piovezana Bossolani, Gleison Daion AU - Piovezana Bossolani GD AD - Department of Morphological Sciences, Universidade Estadual de Maringa, 87020-900, Maringa, Parana, Brazil. FAU - Silva, Bruna Thais AU - Silva BT AD - Department of Morphological Sciences, Universidade Estadual de Maringa, 87020-900, Maringa, Parana, Brazil. FAU - Colombo Martins Perles, Juliana Vanessa AU - Colombo Martins Perles JV AD - Department of Morphological Sciences, Universidade Estadual de Maringa, 87020-900, Maringa, Parana, Brazil. FAU - Lima, Mariana Machado AU - Lima MM AD - Department of Morphological Sciences, Universidade Estadual de Maringa, 87020-900, Maringa, Parana, Brazil. FAU - Vieira Frez, Flavia Cristina AU - Vieira Frez FC AD - Department of Morphological Sciences, Universidade Estadual de Maringa, 87020-900, Maringa, Parana, Brazil. FAU - Garcia de Souza, Sara Raquel AU - Garcia de Souza SR AD - Department of Morphological Sciences, Universidade Estadual de Maringa, 87020-900, Maringa, Parana, Brazil. FAU - Sehaber-Sierakowski, Camila Caviquioli AU - Sehaber-Sierakowski CC AD - Department of Morphological Sciences, Universidade Estadual de Maringa, 87020-900, Maringa, Parana, Brazil. FAU - Bersani-Amado, Ciomar Aparecida AU - Bersani-Amado CA AD - Department of Pharmacology and Therapeutic, Universidade Estadual de Maringa, Maringa, Parana, Brazil. FAU - Zanoni, Jacqueline Nelisis AU - Zanoni JN AD - Department of Morphological Sciences, Universidade Estadual de Maringa, 87020-900, Maringa, Parana, Brazil. Electronic address: jnzanoni@uem.br. LA - eng PT - Journal Article DEP - 20191014 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Neuroprotective Agents) RN - 9IKM0I5T1E (Quercetin) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Antioxidants/pharmacology MH - Arthritis, Experimental/chemically induced/*complications MH - Arthritis, Rheumatoid/*complications MH - Enteric Nervous System/drug effects/pathology MH - Inflammation/*drug therapy/etiology/pathology MH - Jejunum/*drug effects/immunology/pathology MH - Male MH - Neurodegenerative Diseases/*drug therapy/etiology/pathology MH - Neuroprotection/drug effects MH - Neuroprotective Agents/*pharmacology MH - Quercetin/*pharmacology MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Enteric nervous system OT - Glia OT - Quercetin OT - Rheumatoid arthritis EDAT- 2019/10/18 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/10/18 06:00 PHST- 2019/08/21 00:00 [received] PHST- 2019/10/08 00:00 [revised] PHST- 2019/10/10 00:00 [accepted] PHST- 2019/10/18 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/10/18 06:00 [entrez] AID - S0024-3205(19)30883-5 [pii] AID - 10.1016/j.lfs.2019.116956 [doi] PST - ppublish SO - Life Sci. 2019 Dec 1;238:116956. doi: 10.1016/j.lfs.2019.116956. Epub 2019 Oct 14.