Effects of Antirheumatic Drugs on the Development of Experimental AA Amyloidosis in C57BL/6 Mice

  • L Leonaviciene Institute of Experimental and Clinical Medicine of Vilnius University
  • D Povilenaite Institute of Experimental and Clinical Medicine of Vilnius University
  • R Bradunaite Institute of Experimental and Clinical Medicine of Vilnius University
  • D Vaitkiene Institute of Experimental and Clinical Medicine of Vilnius University and Faculty of Medicine, Vilnius University

Abstract

Because there is no known specific effective therapy for secondary amyloidosis at the present time, the aim  of this study was to determine whether antirheumatic drugs inhibit the development of experimental AA  amyloidosis, induced in a C57BL/6 mice by injections of casein and fibrin. Monotherapy with sulfasalazine  (SSL) and diclofenac (D) and combined treatment with diclofenac and prednisolone (D/P) by using  prophylactic and therapeutic treatment protocols were investigated. The drugs were administered through  intragastric gavage 5 times a week for 5 or 6 weeks in the following doses: D - 1 mg/kg, P - 10 mg/kg,  and SSL - 100 mg/kg. 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. 

Our study indicated that no positive effect from prophylactic treatment with D could be seen on amyloid  deposition in investigated organs. Prophylactic combined treatment with D/P resulted in significant improvement  of disease symptoms and markedly reduced amyloid deposits in the spleen, kidneys, and liver (P  < 0.02-0.001). SSL therapy alone has been more successful in the prophylactic treatment of experimental  amyloidosis: the decrease of amyloid deposits was statistically significant in all investigated organs (P <  0.04 – 0.001) and the most suppression of amyloid formation in the kidneys and liver was observed (P <  0.004-0.001). In therapeutic treatment of experimental amyloidosis, combined treatment with D/P showed  the most inhibition of amyloid formation in the internal organs (P < 0.006 – 0.001). The highest suppression  (by 86.7%; P < 0.001) of amyloid deposits was observed 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). 

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. 

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