The combined treatment of praziquantel with osteopontin immunoneutralization reduces liver damage inSchistosoma japonicum-infected mice

Abstract

The aim of this study was to evaluate the therapeutic effects of osteopontin neutralization treatment on schistosome-induced liver injury in BALB/C mice. We randomly divided 100 BALB/C mice into groups A, B, C, D and group E. Mice in all groups except group A were abdominally infected with schistosomal cercariae to induce a schistosomal hepatopathological model. Mice in group C, D and group E were respectively administered with praziquantel, praziquantel plus colchicine and praziquantel plus neutralizing osteopontin antibody. We extracted mouse liver tissues at 3 and 9 weeks after the 'stool-eggs-positive' day, observed liver histopathological changes by haematoxylin-eosin and Masson trichrome staining and detected the expression of osteopontin, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β1) by immunohistochemistry, RT-PCR and Western blot. We found that praziquantel plus neutralizing osteopontin antibody treatment significantly decreased the granuloma dimension, the percentage of collagen and the expression of osteopontin, α-SMA and TGF-β1 compared to praziquantel plus colchicine treatment in both the acute and chronic stage of schistosomal liver damage (P<0·05). So we believe that the combined regimen of osteopontin immunoneutralization and anti-helminthic treatment can reduce the granulomatous response and liver fibrosis during the schistosomal hepatopathologic course.

Transdermal praziquantel administration attenuates hepatic granulomatosis in mice infected with Schistosoma japonicum

“…On the other hand, without PZQ transdermal administration after killing adult worms, the hepatic fiber content increased in groups C and D (Fig. 6), which was consistent with a previous report (Chen et al 2012). Besides the indirect inhibition of hepatic fibrosis, PZQ could also suppress collagen directly.…”

“…Researchers found that PZQ can decrease the hepatic damage induced by schistosoma eggs, which may be attributed to not only its effect on reducing the number of eggs in the liver by killing adult worms but also its possible anti-granuloma formation and anti-inflammatory properties (Chen et al 2012;Huang et al 2011;Lei et al 2012). PZQ produces a rapid and remarkable improvement in cerebral schistosomiasis japonica and suppresses the inflammatory cells within granulomas in the lung, which cannot be explained on the basis of worm destruction.…”

Role of Osteopontin in Liver Diseases

“…Nevertheless, at late stages, OPN increases the size and the number of hepatic granulomas due to enhanced immune cells recruitment including macrophages, CD4 T cells and DCs into the liver and increased TNFα production 41. Otherwise, OPN neutralization reduces granulomatous response and liver damage via impaired chemotactic function and inflammatory response 42, which suggested that OPN neutralizer acts as the immunosuppression therapy for liver injury with granulomatous responses.…”

A novel green approach for treatment of immature Schistosomiasis Mansoni infection in mice; Arabic gum (Acacia Senegal) antischistosomal properties

“…TGF- β 1 promotes hepatic stellate cell (HSC) proliferation and collagen synthesis in the activated HSC [54] or modulates deposition of extracellular matrix (ECM) components and immune functions [55]. Furthermore, a number of researchers have recognized TGF- β 1 inhibition as one of the factors that can be used to evaluate the antifibrotic effects of drugs on hosts infected with Schistosoma japonicum [56]. Consequently, possible suppression of TGF- β 1 by AG could reverse the immunopathologic effect induced by Schistosoma eggs in the affected tissues as seen in in the current study.…”