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Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats

Tetrathiomolybdate (TM), a drug developed for Wilson's disease, produces an anti-angiogenic and anti-inflammatory effect by reducing systemic copper levels. TM therapy has proved effective in inhibiting the growth of tumors in animal tumor models and in cancer patients. We have hypothesized tha...

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Autores principales: Omoto, Atsushi, Kawahito, Yutaka, Prudovsky, Igor, Tubouchi, Yasunori, Kimura, Mizuho, Ishino, Hidetaka, Wada, Makoto, Yoshida, Makie, Kohno, Masataka, Yoshimura, Rikio, Yoshikawa, Toshikazu, Sano, Hajime
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297562/
https://www.ncbi.nlm.nih.gov/pubmed/16277669
http://dx.doi.org/10.1186/ar1801
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author Omoto, Atsushi
Kawahito, Yutaka
Prudovsky, Igor
Tubouchi, Yasunori
Kimura, Mizuho
Ishino, Hidetaka
Wada, Makoto
Yoshida, Makie
Kohno, Masataka
Yoshimura, Rikio
Yoshikawa, Toshikazu
Sano, Hajime
author_facet Omoto, Atsushi
Kawahito, Yutaka
Prudovsky, Igor
Tubouchi, Yasunori
Kimura, Mizuho
Ishino, Hidetaka
Wada, Makoto
Yoshida, Makie
Kohno, Masataka
Yoshimura, Rikio
Yoshikawa, Toshikazu
Sano, Hajime
author_sort Omoto, Atsushi
collection PubMed
description Tetrathiomolybdate (TM), a drug developed for Wilson's disease, produces an anti-angiogenic and anti-inflammatory effect by reducing systemic copper levels. TM therapy has proved effective in inhibiting the growth of tumors in animal tumor models and in cancer patients. We have hypothesized that TM may be used for the therapy of rheumatoid arthritis and have examined the efficacy of TM on adjuvant-induced arthritis in the rat, which is a model of acute inflammatory arthritis and inflammatory cachexia. TM delayed the onset of and suppressed the severity of clinical arthritis on both paw volume and the arthritis score. Histological examination demonstrated that TM significantly reduces the synovial hyperplasia and inflammatory cell invasion in joint tissues. Interestingly, TM can inhibit the expression of vascular endothelial growth factor in serum synovial tissues, especially in endothelial cells and macrophages. Moreover, the extent of pannus formation, which leads to bone destruction, is correlated with the content of vascular endothelial growth factor in the serum. There was no mortality in TM-treated rat abnormalities. TM also suppressed inflammatory cachexia. We suggest that copper deficiency induced by TM is a potent approach both to inhibit the progression of rheumatoid arthritis with minimal adverse effects and to improve the well-being of rheumatoid arthritis patients.
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spelling pubmed-12975622005-12-01 Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats Omoto, Atsushi Kawahito, Yutaka Prudovsky, Igor Tubouchi, Yasunori Kimura, Mizuho Ishino, Hidetaka Wada, Makoto Yoshida, Makie Kohno, Masataka Yoshimura, Rikio Yoshikawa, Toshikazu Sano, Hajime Arthritis Res Ther Research Article Tetrathiomolybdate (TM), a drug developed for Wilson's disease, produces an anti-angiogenic and anti-inflammatory effect by reducing systemic copper levels. TM therapy has proved effective in inhibiting the growth of tumors in animal tumor models and in cancer patients. We have hypothesized that TM may be used for the therapy of rheumatoid arthritis and have examined the efficacy of TM on adjuvant-induced arthritis in the rat, which is a model of acute inflammatory arthritis and inflammatory cachexia. TM delayed the onset of and suppressed the severity of clinical arthritis on both paw volume and the arthritis score. Histological examination demonstrated that TM significantly reduces the synovial hyperplasia and inflammatory cell invasion in joint tissues. Interestingly, TM can inhibit the expression of vascular endothelial growth factor in serum synovial tissues, especially in endothelial cells and macrophages. Moreover, the extent of pannus formation, which leads to bone destruction, is correlated with the content of vascular endothelial growth factor in the serum. There was no mortality in TM-treated rat abnormalities. TM also suppressed inflammatory cachexia. We suggest that copper deficiency induced by TM is a potent approach both to inhibit the progression of rheumatoid arthritis with minimal adverse effects and to improve the well-being of rheumatoid arthritis patients. BioMed Central 2005 2005-08-08 /pmc/articles/PMC1297562/ /pubmed/16277669 http://dx.doi.org/10.1186/ar1801 Text en Copyright © 2005 Omoto et al.; licensee BioMed Central Ltd.
spellingShingle Research Article
Omoto, Atsushi
Kawahito, Yutaka
Prudovsky, Igor
Tubouchi, Yasunori
Kimura, Mizuho
Ishino, Hidetaka
Wada, Makoto
Yoshida, Makie
Kohno, Masataka
Yoshimura, Rikio
Yoshikawa, Toshikazu
Sano, Hajime
Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats
title Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats
title_full Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats
title_fullStr Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats
title_full_unstemmed Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats
title_short Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats
title_sort copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297562/
https://www.ncbi.nlm.nih.gov/pubmed/16277669
http://dx.doi.org/10.1186/ar1801
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