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Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen
Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease associated with oxidative stress that causes excruciating pain, discomfort, and joint destruction. Ebselen (EB), a synthesized versatile organo-selenium compound, protects cells from reactive oxygen species (ROS)-induced injury...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352177/ https://www.ncbi.nlm.nih.gov/pubmed/37131046 http://dx.doi.org/10.1007/s10787-023-01238-5 |
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author | Thabet, Noura M. Abdel-Rafei, Mohamed K. Amin, Mohamed M. |
author_facet | Thabet, Noura M. Abdel-Rafei, Mohamed K. Amin, Mohamed M. |
author_sort | Thabet, Noura M. |
collection | PubMed |
description | Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease associated with oxidative stress that causes excruciating pain, discomfort, and joint destruction. Ebselen (EB), a synthesized versatile organo-selenium compound, protects cells from reactive oxygen species (ROS)-induced injury by mimicking glutathione peroxidase (GPx) action. This study aimed to investigate the antioxidant and anti-inflammatory effects of EB in an arthritic irradiated model. This goal was achieved by subjecting adjuvant-induced arthritis (AIA) rats to fractionated whole body γ-irradiation (2 Gy/fraction once per week for 3 consecutive weeks, for a total dose of 6 Gy) and treating them with EB (20 mg/kg/day, p.o) or methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) as a reference anti-RA drug. The arthritic clinical signs, oxidative stress and antioxidant biomarkers, inflammatory response, expression of NOD-like receptor protein-3 (NLRP-3) inflammasome, receptor activator of nuclear factor κB ligand (RANKL), nuclear factor-κB (NF-κB), apoptotic indicators (caspase 1 and caspase 3), cartilage integrity marker (collagen-II), and histopathological examination of ankle joints were assessed. EB notably improved the severity of arthritic clinical signs, alleviated joint histopathological lesions, modulated oxidative stress and inflammation in serum and synovium, as well as reduced NLRP-3, RANKL, and caspase3 expression while boosting collagen-II expression in the ankle joints of arthritic and arthritic irradiated rats with comparable potency to MTX. Our findings suggest that EB, through its antioxidant and anti-inflammatory properties, has anti-arthritic and radioprotective properties in an arthritic irradiated model. |
format | Online Article Text |
id | pubmed-10352177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-103521772023-07-19 Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen Thabet, Noura M. Abdel-Rafei, Mohamed K. Amin, Mohamed M. Inflammopharmacology Original Article Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease associated with oxidative stress that causes excruciating pain, discomfort, and joint destruction. Ebselen (EB), a synthesized versatile organo-selenium compound, protects cells from reactive oxygen species (ROS)-induced injury by mimicking glutathione peroxidase (GPx) action. This study aimed to investigate the antioxidant and anti-inflammatory effects of EB in an arthritic irradiated model. This goal was achieved by subjecting adjuvant-induced arthritis (AIA) rats to fractionated whole body γ-irradiation (2 Gy/fraction once per week for 3 consecutive weeks, for a total dose of 6 Gy) and treating them with EB (20 mg/kg/day, p.o) or methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) as a reference anti-RA drug. The arthritic clinical signs, oxidative stress and antioxidant biomarkers, inflammatory response, expression of NOD-like receptor protein-3 (NLRP-3) inflammasome, receptor activator of nuclear factor κB ligand (RANKL), nuclear factor-κB (NF-κB), apoptotic indicators (caspase 1 and caspase 3), cartilage integrity marker (collagen-II), and histopathological examination of ankle joints were assessed. EB notably improved the severity of arthritic clinical signs, alleviated joint histopathological lesions, modulated oxidative stress and inflammation in serum and synovium, as well as reduced NLRP-3, RANKL, and caspase3 expression while boosting collagen-II expression in the ankle joints of arthritic and arthritic irradiated rats with comparable potency to MTX. Our findings suggest that EB, through its antioxidant and anti-inflammatory properties, has anti-arthritic and radioprotective properties in an arthritic irradiated model. Springer International Publishing 2023-05-02 2023 /pmc/articles/PMC10352177/ /pubmed/37131046 http://dx.doi.org/10.1007/s10787-023-01238-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Thabet, Noura M. Abdel-Rafei, Mohamed K. Amin, Mohamed M. Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen |
title | Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen |
title_full | Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen |
title_fullStr | Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen |
title_full_unstemmed | Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen |
title_short | Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen |
title_sort | fractionated whole body γ-irradiation aggravates arthritic severity via boosting nlrp3 and rankl expression in adjuvant-induced arthritis model: the mitigative potential of ebselen |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352177/ https://www.ncbi.nlm.nih.gov/pubmed/37131046 http://dx.doi.org/10.1007/s10787-023-01238-5 |
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