TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and Inflammation

SUMMARY: Rheumatoid arthritis (RA) is considered an autoimmune disease distinguished by chronic synovial membrane inflammation, degraded cartilage, as well as bone destruction, which lead to joints pain and stiffness. The pathogenesis of RA involved at least two mechanisms: Cellular proliferation an...

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Autor principal:	Dawood,Amal F
Lenguaje:	English
Publicado:	Sociedad Chilena de Anatomía 2021
Materias:	Rheumatoid arthritis TDZD-8 Bax Inflammation Rat model
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000100311
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spelling	oai:scielo:S0717-950220210001003112021-03-01TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and InflammationDawood,Amal F Rheumatoid arthritis TDZD-8 Bax Inflammation Rat model SUMMARY: Rheumatoid arthritis (RA) is considered an autoimmune disease distinguished by chronic synovial membrane inflammation, degraded cartilage, as well as bone destruction, which lead to joints pain and stiffness. The pathogenesis of RA involved at least two mechanisms: Cellular proliferation and activation of glycogen synthase kinase-3β (GSK3β) enzyme. Thus, we tested the hypothesis that the GSK3binhibitor, TDZD-8, can treat the synovial tissue toward collagen type II (COII)-mediated RA linked to apoptosis induction and biomarker suppression of inflammation. Wistar rats were immunized with COII (the model group) for 21 days. Matched immunized rats were daily injected with TDZD-8 (1 mg/kg; i.p) for three additional weeks (COII+TDZD- 8).After 42 days of post-immunization, blood and tissues were collected. Histology (H&E) and immunohistochemistry (CD45; leukocyte common antigen) images showed that COII induced RA was demonstrated by profound damage to the synovial tissue and infiltration of the inflammatory cells, which were substantially ameliorated with TDZD-8. In addition, COII immunization caused the induction of rheumatoid factor (RF), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin 1 beta (IL-1β) that were substantially (p<0.05) suppressed by TDZD-8. Whereas, TDZD-8 augmented the apoptotic biomarker, Bcl-2-associated X protein (Bax), which was significantly (p<0.05) ameliorated by RA. We also showed a substantial relationship (p<0.001) between the blood levels of RF and the synovial tissue levels of TNF-α (r = 0.759), IL-1b (r = 0.969), IL-6 (r = 0.749), and Bax (r = - 0.914). These results indicate effective treatment of the injured synovial tissue by TDZD-8 against COII-induced RA in rats, which also decreases inflammatory biomarkers and augmentation of apoptosis.info:eu-repo/semantics/openAccessSociedad Chilena de AnatomíaInternational Journal of Morphology v.39 n.1 20212021-02-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000100311en10.4067/S0717-95022021000100311
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Rheumatoid arthritis TDZD-8 Bax Inflammation Rat model
spellingShingle	Rheumatoid arthritis TDZD-8 Bax Inflammation Rat model Dawood,Amal F TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and Inflammation
description	SUMMARY: Rheumatoid arthritis (RA) is considered an autoimmune disease distinguished by chronic synovial membrane inflammation, degraded cartilage, as well as bone destruction, which lead to joints pain and stiffness. The pathogenesis of RA involved at least two mechanisms: Cellular proliferation and activation of glycogen synthase kinase-3β (GSK3β) enzyme. Thus, we tested the hypothesis that the GSK3binhibitor, TDZD-8, can treat the synovial tissue toward collagen type II (COII)-mediated RA linked to apoptosis induction and biomarker suppression of inflammation. Wistar rats were immunized with COII (the model group) for 21 days. Matched immunized rats were daily injected with TDZD-8 (1 mg/kg; i.p) for three additional weeks (COII+TDZD- 8).After 42 days of post-immunization, blood and tissues were collected. Histology (H&E) and immunohistochemistry (CD45; leukocyte common antigen) images showed that COII induced RA was demonstrated by profound damage to the synovial tissue and infiltration of the inflammatory cells, which were substantially ameliorated with TDZD-8. In addition, COII immunization caused the induction of rheumatoid factor (RF), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin 1 beta (IL-1β) that were substantially (p<0.05) suppressed by TDZD-8. Whereas, TDZD-8 augmented the apoptotic biomarker, Bcl-2-associated X protein (Bax), which was significantly (p<0.05) ameliorated by RA. We also showed a substantial relationship (p<0.001) between the blood levels of RF and the synovial tissue levels of TNF-α (r = 0.759), IL-1b (r = 0.969), IL-6 (r = 0.749), and Bax (r = - 0.914). These results indicate effective treatment of the injured synovial tissue by TDZD-8 against COII-induced RA in rats, which also decreases inflammatory biomarkers and augmentation of apoptosis.
author	Dawood,Amal F
author_facet	Dawood,Amal F
author_sort	Dawood,Amal F
title	TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and Inflammation
title_short	TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and Inflammation
title_full	TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and Inflammation
title_fullStr	TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and Inflammation
title_full_unstemmed	TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and Inflammation
title_sort	tdzd-8 suppresses rheumatoid arthritis induced by collagen type ii in rats: potential role of apoptosis and inflammation
publisher	Sociedad Chilena de Anatomía
publishDate	2021
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000100311
work_keys_str_mv	AT dawoodamalf tdzd8suppressesrheumatoidarthritisinducedbycollagentypeiiinratspotentialroleofapoptosisandinflammation
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TDZD-8 Suppresses Rheumatoid Arthritis Induced by Collagen Type II in Rats: Potential Role of Apoptosis and Inflammation

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