Inhibition of the second phase of amyloidogenesis in a mouse model by a single-dose colchicine regimen

Citation
S. Shtrasburg et al., Inhibition of the second phase of amyloidogenesis in a mouse model by a single-dose colchicine regimen, J LA CL MED, 138(2), 2001, pp. 107-111
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
ISSN journal
0022-2143 → ACNP
Volume
138
Issue
2
Year of publication
2001
Pages
107 - 111
Database
ISI
SICI code
0022-2143(200108)138:2<107:IOTSPO>2.0.ZU;2-V
Abstract
Amyloidogenesis consists of two stages. In the first, amyloid enhancing fac tor (AEF) is generated, and in the second, deposition of amyloid fibrils oc curs. Colchicine is a known inhibitor of amyloidosis of familial Mediterran ean fever (FMF) and of mouse experimental amyloidosis, but the timing and m echanism of its effect are still unclear. The aim of this study is to deter mine whether colchicine inhibits the second phase of amyloidogenesis and to study the time correlate of such an effect. To that end, amyloid was induc ed in Swiss male mice with AEF and AgNO3 (an inflammatory stimulus), a meth od that skips the first phase of amyloidogenesis. Two amyloid induction pro tocols were used: a standard protocol, in which AEF and AgNO3 were administ ered concurrently, and a prolonged protocol, in which the administration of AgNO3 was delayed by 24 hours or 7 days. To study the inhibitory effect of colchicine on the second phase of amyloidogenesis, a single dose of colchi cine (30 mug) was injected intravenously before, during, or after administr ation of AgNo3 in both the standard and prolonged amyloid induction protoco ls. The amount of amyloid deposition in the spleens was determined with the crush-and-smear technique and a 5-grade scale. Colchicine was found to inh ibit the second phase of amyloidogenesis. Its best effect was achieved when administered 48 hours after initiation of AgNO3 injections. The pattern of colchicine-inhibition-in-time in the standard and the prolonged amyloid in duction protocols was similar, indicating that colchicine exerts inhibition through its effect on the inflammatory stimulus (AgNO3). These findings su ggest that (1) colchicine suppresses amyloidogenesis in the late (second) s tage and that (2) this suppression is possibly related to the anti-inflamma tory effect of colchicine.