Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Treatment of experimental amyloidosis with antirheumatic drugs

Treatment of experimental amyloidosis with antirheumatic drugs Treatment of experimental amyloidosis with antirheumatic drugs Background. Because at present there is no known specific effective therapy for secondary amyloidosis, the aim of this study was to determine whether antirheumatic drugs inhibit the development of experimental AA amyloidosis induced in C57BL/6 mice by casein and fibrin injections. Materials and methods. Monotherapy with sulfasalazine (SSL) and diclofenac (D) and a combined treatment with diclofenac and prednisolone (D/P) according to prophylactic and therapeutic treatment protocols were investigated. The drugs were administered through intragastric gavage 5 times a week for 5 or 4 weeks in the following doses: D - 1 mg/kg, P - 10 mg/kg, and SSL - 100 mg/kg. A histopathological examination of splenic, kidney and hepatic tissues of mice was performed. The amount of amyloid was assessed semi-quantitatively by polarizing microscopy after Congo red staining. Results. Our study indicated that no positive effect of the prophylactic treatment with D could be seen on amyloid deposition in the target organs. Prophylactic combined treatment with D/P resulted in a significant improvement of disease symptoms and markedly reduced amyloid deposits in the spleen, kidneys and liver (p < 0.02-0.001). SSL therapy alone was more successful in the prophylactic treatment of experimental amyloidosis: the decrease of amyloid deposits was statistically significant in all examined organs (p < 0.04-0.001), and the suppression of amyloid formation was most significant in the kidneys and liver (p < 0.004-0.001). In the therapeutic treatment of experimental amyloidosis, combined treatment with D/P showed the most pronounced inhibition of amyloid formation in the internal organs (p < 0.006-0.001). The suppression (by 86.7%; p < 0.001) of amyloid deposits was most notable in the liver. Treatment of mice with D alone produced a significant reduction in amyloid deposition only in the liver (p < 0.03) and with SSL only in the spleen (p < 0.03). Conclusions. These findings suggest that D/P and SSL at relevant doses suppress amyloidogenesis, and this suppression is possibly related to the anti-inflammatory effect of antirheumatic drugs. Although these drugs cannot completely inhibit the disease in this model, a possibility remains that they may be clinically useful in rheumatic diseases associated with the formation of amyloidogenic derivatives. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Acta Medica Lithuanica de Gruyter

Treatment of experimental amyloidosis with antirheumatic drugs

Download PDF
13 pages

Loading next page...
 
/lp/de-gruyter/treatment-of-experimental-amyloidosis-with-antirheumatic-drugs-GvJuPNaVGn
Publisher
de Gruyter
Copyright
Copyright © 2010 by the
ISSN
1392-0138
eISSN
2029-4174
DOI
10.2478/v10140-010-0003-y
Publisher site
See Article on Publisher Site

Abstract

Treatment of experimental amyloidosis with antirheumatic drugs Background. Because at present there is no known specific effective therapy for secondary amyloidosis, the aim of this study was to determine whether antirheumatic drugs inhibit the development of experimental AA amyloidosis induced in C57BL/6 mice by casein and fibrin injections. Materials and methods. Monotherapy with sulfasalazine (SSL) and diclofenac (D) and a combined treatment with diclofenac and prednisolone (D/P) according to prophylactic and therapeutic treatment protocols were investigated. The drugs were administered through intragastric gavage 5 times a week for 5 or 4 weeks in the following doses: D - 1 mg/kg, P - 10 mg/kg, and SSL - 100 mg/kg. A histopathological examination of splenic, kidney and hepatic tissues of mice was performed. The amount of amyloid was assessed semi-quantitatively by polarizing microscopy after Congo red staining. Results. Our study indicated that no positive effect of the prophylactic treatment with D could be seen on amyloid deposition in the target organs. Prophylactic combined treatment with D/P resulted in a significant improvement of disease symptoms and markedly reduced amyloid deposits in the spleen, kidneys and liver (p < 0.02-0.001). SSL therapy alone was more successful in the prophylactic treatment of experimental amyloidosis: the decrease of amyloid deposits was statistically significant in all examined organs (p < 0.04-0.001), and the suppression of amyloid formation was most significant in the kidneys and liver (p < 0.004-0.001). In the therapeutic treatment of experimental amyloidosis, combined treatment with D/P showed the most pronounced inhibition of amyloid formation in the internal organs (p < 0.006-0.001). The suppression (by 86.7%; p < 0.001) of amyloid deposits was most notable in the liver. Treatment of mice with D alone produced a significant reduction in amyloid deposition only in the liver (p < 0.03) and with SSL only in the spleen (p < 0.03). Conclusions. These findings suggest that D/P and SSL at relevant doses suppress amyloidogenesis, and this suppression is possibly related to the anti-inflammatory effect of antirheumatic drugs. Although these drugs cannot completely inhibit the disease in this model, a possibility remains that they may be clinically useful in rheumatic diseases associated with the formation of amyloidogenic derivatives.

Journal

Acta Medica Lithuanica – de Gruyter

Published: Jun 29, 2010

References

  • Natural history and outcome in systemic AA amyloidosis
    H. Lachman
  • Amyloidosis and auto-inflammatory syndromes
    C. Grateou
  • Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism
    K. Lundmark
  • Amyloidosis in a nationwide series of 1666 subjects with rheumatoid arthritis who died during 1989 in Finland
    R. Myllykangas-Lousujarvi
  • Phenotypes and fibril types in systemic amyloidosis. Clinicopathology of Amyloidosis
    P. Hawkins
  • Clinical strategies for amyloid A amyloidosis secondary to rheumatoid arthritis
    T. Nakamura
  • AA amyloidogenesis a progress report and possible future directions
    R. Kisilevsky
  • Inactivation of amyloid-enhancing factor (AEF): study on experimental murine AA amyloidosis
    M. Omoto
  • Lovastatin inhibits formation of AA amyloid
    J. Van der Hilst
  • Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model
    P. Westermark
  • Anti-amyloid drugs: potential in the treatment of diseases associated with aging
    R. Kisilevsky
  • AA-amyloidosis can be transferred by peripheral blood monocytes
    J. Sponarova
  • Fibrate inhibits reactive AA-amyloidosis in mice
    T. Yamada
  • Colchicine treatment of AA amyloidosis of familian Mediterranean fever
    A. Livneh
  • Experimental AA-Amyloidosis in mice is inhibited by treatment with the anti-rheumatic drug tenidap
    A. Husebekk
  • Inhibition of the second phase of amyloidogenesis in a mouse model by a single-dose colchicine regimen
    S. Shtrasburg
  • Influence of dextran sulphate, fibrin, and ubiquitin on the development of casein-induced experimental AA amyloidosis in C57BL/6 mice
    L. Leonaviciene
  • Staining of amyloid by buffered Congo red in 50% ethanol
    H. Eastwood
  • An ancillary tool for the diagnosis of animal AA amyloidosis
    S. Shtrasburg
  • Prevalence of secondary amyloidosis in Asian North Indian patients with rheumatoid arthritis
    A. Wakhlu
  • Kinetics of proteoglycans and glycosaminoglycans in AA amyloidosis
    T. Wien
  • AA amyloid deposition is complement independent
    W. Hutchinson
  • New thoughts on proteinuria and management of glomerulonephritis
    G. Grauer
  • Clinical features associated with correction of T-cell senescence: increased acute-phase response, amyloidosis and arthritis
    J. Mountz
  • COX-2 inhibition: not too hot, not too cold - (perhaps) just right
    V. Bakowsky
  • Distinct isoforms (COX-1 and COX-2) of cyclooxygenase: possible physiological and therapeutic implications
    M. Pairet
  • Cyclooxygenase-2 inhibitors: rationale and therapeutic potential for Alzheimer's disease
    P. McGeer
  • Experimental models used to investigate the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2 by non-steroidal anti-inflammatory drugs
    M. Pairet
  • Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal antiinflammatory drug-related nephrotoxicity
    K. Khan
  • Clinical experience with specific COX-2 inhibitors in arthritis
    L. Crofford
  • Induction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity to nonsteroid anti-inflammatory drugs
    D. Simmons
  • Nonsteroidal anti-inflammatory drugs, acetaminophen, cyclooxygenase 2, and fever
    D. Simmons