Effect of Colchicine on Schistosoma-lnduced Renal Amyloidosis in Syrian Golden Hamsters

Abstract

Seventy Syrian golden hamsters were infected with Schistosoma haematobium, and 10 uninfected hamsters served as negative controls. Of the schistosome-infected hamsters, 10 served as positive controls (infected but untreated) and the rest (60 hamsters) received treatment. In 30 hamsters treatment was given 9 weeks after infection (before the appearance of renal amyloidosis) and in the other 30 it was given after the appearance of amyloid deposits, 15 weeks after infection. Each treatment group was subdivided into 3 groups (10 hamsters each) in which treatment was either antischistosomal alone, combined anti-schistosomal and colchicine, or colchicine alone. Eighteen weeks after infection half of the animals in each group were sacrificed, while the rest were sacrificed 24 weeks after infection. Kidney specimens were evaluated semiquantitatively for renal amyloid deposits. Significant reductions in renal amyloid deposits and proteinuria were observed when combined treatment was given. This was nearly complete with early treatment and only partial when treatment was given late. When colchicine was given alone, a partial but significant reduction in proteinuria with no recognizable effect on renal amyloid deposits was observed. We conclude that colchicine is effective for the prevention and cure of schistosome-related renal amyloidosis in golden hamsters.

Colchicine Suppresses Osteopontin Expression and Inflammatory Cell Infiltration in Chronic Cyclosporine Nephrotoxicity

“…Favari et al [25]and Kershenobich et al [26]reported that a number of liver injuries can be improved by colchicine intervention. In the kidney, colchicine has been shown to prevent various renal injuries, including amyloidosis with proteinuria [27], renal scarring postbacterial infection [28], antiglomerular basement membrane nephritis [29]and chronic CsA nephrotoxicity [30]. However, its modes of action have not been fully explored.…”

Effect of Colchicine on Chronic Ciclosporin Nephrotoxicity in Sprague-Dawley Rats

“…Colchicine has been recently reported to prevent amyloidosis secondary to familial Mediterranean fever in humans [15] and amyloidosis secondary to Schistosoma infection in hamsters [5]. More specific to our target is that colchicine has been reported to suppress renal scarring in E. coli infected rats [6] and to be effective in preventing the acute progression of renal insufficiency and tubulointerstitial fibrosis in an experimental model of glomerulonephritis in the rabbit [8].…”

“…Colchicine, which is an old drug used essentially for the alleviation of pain in acute gout and to suppress attacks of familial Mediterranean fever, has been recently reported to prevent schistosoma-related amyloidosis in Syrian golden hamsters [5] and renal scarring induced in rats by Escherichia coli pyelonephritis [6]. In addition, colchicine has been used with some success in the management of experimental and clinical hepatic fibrosis [7].…”

The changing face of schistosomal glomerulopathy

“…Amyloidosis occurs with prolonged active infection with either S. hematobium or S. mansoni in humans, as it does in several animal models [33]. Like other inflammation-associated amyloids, AA beta-pleated fibrils are deposited preferentially in the kidney, liver, subcutaneous fat, and gums.…”

“…The kidneys are shrunken in 25% of patients, in whom there is associated schistosomal interstitial fibrosis. No evidence indicates that the course of schistosoma-associated amyloidosis can be modified by any form of treatment [33].…”