Effect of colchicine on experimental amyloidosis in two CBA/J mouse models. Chronic inflammatory stimulation and administration of amyloid-enhancing factor during acute inflammation.
|
| Abstract |
To investigate the mechanism of action of colchicine in blocking amyloid deposition, two model systems of amyloidosis in CBA/J mice were studied. In experimental chronic inflammation, daily injection of silver nitrate (AgNO3) resulted in the deposition of 667 +/- 68 ng of amyloid A protein (AA)/mg of spleen after 25 days. Treatment with 10 micrograms of colchicine daily decreased AgNO3-induced AA deposition to 12 +/- 1 ng of AA/mg of spleen (p less than 0.001). Colchicine diminished the acute phase serum amyloid A protein (SAA) response after 24 hours. Over a 25-day period, SAA concentrations declined and approached baseline both in colchicine-treated and (unexpectedly) in control mice. This suggested that suppression of SAA levels was not the primary event inhibiting amyloid deposition. In a model of accelerated amyloid deposition, injection of preformed amyloid-enhancing factor along with AgNO3 induced the deposition of 974 +/- 46 ng of AA/mg of spleen 48 hours later. Colchicine only partially decreased amyloid-enhancing factor-induced amyloid deposition to 578 +/- 91 ng of AA/mg of spleen, while blunting the acute phase SAA response. These results suggest that colchicine inhibits amyloidosis in the predeposition phase, possibly by blocking formation of amyloid-enhancing factor.
|
|---|---|
| Authors | S R Brandwein, J D Sipe, M Skinner, A S Cohen |
| Journal | Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 52 Issue 3 Pg. 319-25 (Mar 1985) ISSN: 0023-6837 [Print] United States |
| PMID | 3974202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!