TY - JOUR
T1 - Inhibition of the second phase of amyloidogenesis in a mouse model by a single-dose colchicine regimen
AU - Shtrasburg, Shmuel
AU - Pras, Mordechai
AU - Gal, Rivka
AU - Salai, Moshe
AU - Livneh, Avi
PY - 2001
Y1 - 2001
N2 - Amyloidogenesis consists of two stages. In the first, amyloid enhancing factor (AEF) is generated, and in the second, deposition of amyloid fibrils occurs. Colchicine is a known inhibitor of amyloidosis of familial Mediterranean fever (FMF) and of mouse experimental amyloidosis, but the timing and mechanism of its effect are still unclear. The aim of this study is to determine whether colchicine inhibits the second phase of amyloidogenesis and to study the time correlate of such an effect. To that end, amyloid was induced in Swiss male mice with AEF and AgNO3 (an inflammatory stimulus), a method that skips the first phase of amyloidogenesis. Two amyloid induction protocols were used: a standard protocol, in which AEF and AgNO3 were administered 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 colchicine (30 μg) was injected intravenously before, during, or after administration of AgNO3 in both the standard and prolonged amyloid induction protocols. 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 inhibit 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 induction protocols was similar, indicating that colchicine exerts inhibition through its effect on the inflammatory stimulus (AgNO3). These findings suggest that (1) colchicine suppresses amyloidogenesis in the late (second) stage and that (2) this suppression is possibly related to the anti-inflammatory effect of colchicine.
AB - Amyloidogenesis consists of two stages. In the first, amyloid enhancing factor (AEF) is generated, and in the second, deposition of amyloid fibrils occurs. Colchicine is a known inhibitor of amyloidosis of familial Mediterranean fever (FMF) and of mouse experimental amyloidosis, but the timing and mechanism of its effect are still unclear. The aim of this study is to determine whether colchicine inhibits the second phase of amyloidogenesis and to study the time correlate of such an effect. To that end, amyloid was induced in Swiss male mice with AEF and AgNO3 (an inflammatory stimulus), a method that skips the first phase of amyloidogenesis. Two amyloid induction protocols were used: a standard protocol, in which AEF and AgNO3 were administered 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 colchicine (30 μg) was injected intravenously before, during, or after administration of AgNO3 in both the standard and prolonged amyloid induction protocols. 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 inhibit 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 induction protocols was similar, indicating that colchicine exerts inhibition through its effect on the inflammatory stimulus (AgNO3). These findings suggest that (1) colchicine suppresses amyloidogenesis in the late (second) stage and that (2) this suppression is possibly related to the anti-inflammatory effect of colchicine.
UR - http://www.scopus.com/inward/record.url?scp=0034921116&partnerID=8YFLogxK
U2 - 10.1067/mlc.2001.116488
DO - 10.1067/mlc.2001.116488
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:0034921116
SN - 0022-2143
VL - 138
SP - 107
EP - 111
JO - Journal of Laboratory and Clinical Medicine
JF - Journal of Laboratory and Clinical Medicine
IS - 2
ER -