Effect of Fasciola hepatica proteins on the functioning of rat hepatocytes

Abstract

Fasciolosis is a hepatic parasitic infection that affects many mammal species and creates a great economic and veterinary problem. Molecular mechanisms of parasite–hepatocyte interactions have not been precisely characterized yet. Therefore, the aim of the study was to investigate alterations in the metabolic activity of rat liver cells exposed to Fasciola hepatica somatic proteins. Hepatocytes were incubated with 0–1 mg/ml of fluke's somatic proteins for various periods of time. Afterward, changes in hepatocytes metabolic activity were determined with MTT and enzyme leakage tests. Hepatocytes' capacity to synthesize albumin was also investigated. It was observed that protein concentration, as well as longevity of their action, influenced metabolic activity of rat liver cells. Diminution of hepatocytes survival rate, an increase in enzyme leakage and altered synthetic capacity after treatment with parasite's proteins were reported. It is concluded that somatic proteins of F. hepatica may play an important role in liver cell damaging.

Excretory/secretory products of Fasciola hepatica but not recombinant phosphoglycerate kinase induce death of human hepatocyte cells

“…Our results are consistent with those achieved by Gajewska et al (2006) who showed that rat hepatocyte cell death is caused by FhES products. Similar results have also been obtained when rat liver cells were treated with homogenate of adult F. hepatica (Wesołowska et al 2012). Several proteomic studies on the composition of F. hepatica ES have been undertaken in recent years, and numerous proteins have been found in adult F. hepatica ES, the most abundant of which appear to be the cathepsin L proteases which have been shown to digest basement membrane and extracellular matrix proteins including collagen, fibronectin and laminin, suggesting Fasciola hepatica ES (A) produced dose-dependent death of Hep-G2 cells, whereas this effect was not observed for cells treated with FhPGK (B) Cytotoxicity of Fasciola hepatica ES 217 roles in migration (Berasain et al 1997;Norbury et al 2011).…”

“…It is now known that FhES components can induce alternatively activated macrophages (Donnelly et al 2005;Flynn et al 2007), and apoptosis of peritoneal macrophages (Guasconi et al 2012) and eosinophils (Serradell et al 2009). There are only limited data concerning the effects of F. hepatica proteins on hepatocytes; it has been shown that both somatic (Wesołowska et al 2012) and FhES (Gajewska et al 2006) fractions influence survival of rat hepatocytes in vitro. In this study we determined the cytotoxic potential of FhES and the strictly intracellular protein -phosphoglycerate kinase (FhPGK) on Hep-G2 cells (a human hepatocyte cell line).…”

“…The results of the current study clearly indicate that somatic FhPGK has no role in decreased hepatocyte cell survival in vitro. Wesołowska et al (2012) reported that adult fluke somatic proteins diminished rat hepatocyte viability in vitro even with a concentration of 20 µg/ml. This effect may have been caused due to other undefined somatic compounds and/or secretory proteins still present in secretory glands of the fluke.…”

Dynamics of liver enzymes in rabbits experimentally infected with <i>Fasciola</i> sp. (Intermediate form from Japan)

“…The highest ALP activity is found on the border membranes of the bile duct whereas GGT is found in the hepatocytes and biliary epithelial cell [ 8 , 12 ]. Increased level of these enzymes is an indicator of hepatobiliary injury, epithelial damage and stasis of the bile duct [ 8 , 17 , 27 ]. There are many previous studies on serum liver enzymes of sheep, cattle and monkey infected with F. hepatica and F. gigantica, but few on dynamics of serum liver enzymes in rabbit fascioliasis [ 5 , 6 , 7 , 9 , 17 , 24 , 25 , 29 ].…”

The immune modulatory peptide FhHDM‐1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages

“…The resultant uncontrolled and excessive production of IL‐1κ mediates several proinflammatory disorders with severe pathologic outcomes (37). The migration of F. he‐ patica through the host's liver results in significant tissue damage (38, 39), and the parasite's secretions can induce hepatocyte cell death (40, 41). Inflammation and fibrosis in the liver is typically associated with excessive NLRP3 inflammasome activity, culminating in hepatocyte destruction via pyroptosis and IL‐1β secretion (42).…”