Capillaria hepatica-induced septal fibrosis in rats: a contribution to the study of liver fibrogenesis

Valter Lucas Chaves Barbosa,Zilton De Araújo Andrade

doi:10.1590/s0037-86822010000500006

Valter Lucas Chaves Barbosa, Zilton De Araújo Andrade

Open Access

https://doi.org/10.1590/s0037-86822010000500006

Copy DOI

Abstract

Septal fibrosis of the liver regularly develops in rats infected with the nematode Capillaria hepatica. Curative treatment of the infection prevents the development of septal fibrosis when intervention occurs up to postinfection day (PID) 15, but not later. The present investigation aimed to demonstrate which parasitic factors are present when the process of septal fibrosis can no longer be prevented by curative treatment. Wistar rats were infected with 600 embryonated eggs of C. hepatica administered by gavage and treated with ivermectin and mebendazole in separate groups at PIDs 10, 12, 15, 17 or 20. Rats from each group and their nontreated controls, were killed and examined 40 days after the end of treatment. Findings by PID 15 were compatible with the stage of complete maturation of infection, when worms and eggs were fully developed and a complex host-parasite multifocal necroinflammatory reaction showed greater intensity, but with no signs of septal fibrosis, which appeared from PID 17 onward. Since the worms spontaneously died by PID 15, not only septal fibrosis production, but also its maintenance and further development appeared dependent on the presence of eggs, which were the only parasitic factor remaining thereafter.

Highlights

Septal fibrosis of the liver regularly develops in rats infected with the nematode Capillaria hepatica
By postinfection day (PID) 21, all adult worms were exhibiting signs of disintegration. This process of septal fibrosis became evident in specimens examined following day 17 of infection, when connections between portal to portal spaces occurred at several instances (Figure 3)
Rats treated after PID 17 presented a characteristic picture of septal fibrosis, when examined 40 days after treatment and cure

Summary

Introduction

Septal fibrosis of the liver regularly develops in rats infected with the nematode Capillaria hepatica. The experimental model for hepatic septal fibrosis, which invariably develops in rats following infection with the nematode Capillaria hepatica, has already been applied to the study of several aspects of the pathogenesis of hepatic fibrosis[1,2,3,4,5,6] since its first description in 19937 One advantage of this experimental method lies on its regularity of development, since hepatic fibrosis starts around 16-20 days following infection, establishing portal to portal connections and soon involving the entire liver. Some type of unknown chemical mediator or mediators seems to be at play in between the focal parenchymal parasite-dependent lesions and the portal spaces Another curious detail is that, the infection is self-limited, since the worms die and disintegrate soon after egg-laying, the process of fibrosis continues to present signs of progression thereafter. These are intriguing aspects related to the pathogenesis of fibrosis in this model, which require investigation

Methods

Results

Conclusion