Experimental schistosomiasis mansoni: modulation of granulomas by inhibition of collagen cross-link formation. Preliminary report.

Abstract

beta-Aminopropionitrile (BAPN) is an inhibitor of the lysyl oxidase required for cross-link formation in collagen maturation. The efficacy of BAPN, alone or in association with the anti-schistosomal drug, praziquantel (PZQ), was primarily assessed by measuring the reduction in liver and intestinal egg loads in murine schistosomiasis mansoni. Depending on the treatment group (PZQ, BAPN, BAPN + PZQ), organ-specific effects were observed using microscope image analysis. Most notable was the relatively small size of granulomas in the livers of BAPN-treated mice, which contrasted with the relatively large size and irregular shape of the granulomas in the intestinal tissues of these mice. Mice treated with the combination of BAPN and PZQ had decreased liver and spleen weights, and a significant reduction in the number of eggs trapped in both the liver (86%) and the intestine (99.1%), compared with untreated mice and those given PZQ alone. The lowest number of living eggs/g of tissue in both the liver and intestine was recorded in the combined BAPN + PZQ-treated group. These results suggest that the concurren treatment of infected mice with PZQ and BAPN enhances the release of eggs trapped in the intestine and also results in a significant reduction of liver egg load. The mechanism by which BAPN reduces the number of liver granulomas in PZQ-treated mice is currently being investigated.