Pathogenesis of hepatic septal fibrosis associated with Capillaria hepatica infection of rats

Abstract

Septal fibrosis is a common form of hepatic fibrosis, but its etiology and pathogenesis are poorly understood. Rats infected with the helminth Capillaria hepatica constitute a good experimental model of such fibrosis. To investigate the pathogenetic contribution of the several parasitic factors involved, the following procedures were performed in rats: a) regarding the role of eggs, these were isolated and injected either into the peritoneal cavity or directly into the liver parenchyma; b) for worms alone, 15-day-old infection was treated with mebendazole, killing the parasites before oviposition started; c) for both eggs and worms, rats at the 30th day of infection were treated with either mebendazole or ivermectin. Eggs only originated focal fibrosis from cicatricial granulomas, but no septal fibrosis. Worms alone induced a mild degree of perifocal septal fibrosis. Systematized septal fibrosis of the liver, similar to that observed in the infected controls, occurred only in the rats treated with mebendazole or ivermectin, with dead worms and immature eggs in their livers. Thus, future search for fibrogenic factors associated with C. hepatica infection in rats should consider lesions with both eggs and worms.

Experimental hepatic fibrosis due to Capillaria hepatica infection (differential features presented by rats and mice)

“…Actually, the C. hepatica and the pig-serum models are the two models of septal fibrosis being used in experimental investigations. C. hepatica-induced-septal fibrosis has been revealed as a good model for testing anti-fibrosis drugs and for studies on pathogenesis of hepatic fibrosis (Souza et al 2000, 2001, Santos et al 2001, Lemos et al 2003.…”

“…Besides the focal necro-inflammatory parasitic lesions, caused by groups of worms that usually die and disintegrate within the liver soon after egg lying, there also occurs the development of septal fibrosis throughout the liver, a change that appears in all infected rats (Oliveira & Andrade 2001). The model has permitted studies on pathogenesis (Santos et al 2001, Lemos et al 2003, on response to drugs (Souza et al 2000,2001) and on other aspects (Ferreira & Andrade 1993, Oliveira & Andrade 2001. However, the potential of the model is somewhat limited by the peculiarities connected with the experimental host -the rat -because of the difficulties related to the obtaining of commercial kits to study cytokines, chemokines, receptors, growth factors, cells and extra-cellular tissue markers, and so on.…”

Capillaria hepatica in rats: focal parasitic hepatic lesions and septal fibrosis run independent courses

“…However, these two lesions are related to a same cause. If the worms are destroyed by chemotherapy before egg lying or if the parasitic focal lesions are induced by the direct injections of immature eggs into the peritoneal cavity, portal vein or into the liver tissue itself, focal lesions are formed, but septal fibrosis fails to develop (Santos et al 2001). Therefore, lesions produced by both worms and eggs are necessary for the development of septal fibrosis.…”

Production of septal fibrosis of the liver by means of foreign protein injections into rats

“…septal fibrosis in rats 16 . By injecting purified immature eggs directly into the liver, or by killing the worms before oviposition by means of chemotherapy, Santos et al 15 demonstrated that the presence of lesions containing both disintegrating worms and eggs appeared essential for the full development of disseminated or systematized C. hepatica-induced septal fibrosis of the liver in rats. Therefore, not only the parasitic elements, but the products originated from host-parasite interactions, appeared to play a decisive role in the pathogenesis of septal fibrosis of the liver associated with C. hepatica infection of rats.…”