Cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin

Abstract

The purpose of this study was to determine cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin. The study was conducted upon 100 mice that were divided into five groups; 20 each: uninfected control group, Schistosoma mansoni infected untreated mice (infected control), infected mice treated with praziquantel (PZQ), infected mice treated with silymarin and infected mice treated with both praziquantel and silymarin. 10 mice from each group were sacrificed at 10th and 18th weeks post infection respectively. Histopathological investigations were performed. Liver sections were stained with hematoxylin-eosin and Masson's trichrome stain to evaluate changes of granuloma sizes and numbers. Serum levels of the cytokines (TNF-a, IFN-c, IL-4 and TGF-b1) were assessed in the sera of all groups by immunoassay. The measured levels of cytokines (IFN-c, IL-4, TNF-a, TGF-b1) were found to be significantly increased in infected mice compared to normal control. At the same time, treated groups with silymarin alone or combined with PZQ showed significant decrease in IL-4, TNF-a and TGF-b1 levels compared to infected control. On the other hand, there was a significant increase in IFN-c level observed in all treated groups compared to infected control. In addition, the histopathological examination of the liver in the group treated with PZQ showed a reduction in the number of livers eggs granuloma at all periods of sacrification compared with the infected untreated group. However, there was more decrease in granulomas diameter in both silymarin treated group or combined with PZQ at all periods of sacrification when compared to infected untreated group. In conclusion; treatment with silymarin combined with PZQ in murine schistosomiasis could reduce hepatic fibrosis by their action on the production of pro-inflammatory cytokines.

Immunopathological effects of some Biomphalaria pfeifferi proteins against Schistosoma mansoni infection in BALB/c mice

“…TNF is also responsible to hosts response to infectious agents and recruitment of leukocytes at the inflammation sites (El-Sayed et al, 2016). In this study, the levels of TNF were present throughout the experiment period.…”

“…This could explain the low recovery of worms due to the fact that it is responsible for recruitment of leukocytes and the presence of IFN-γ. It could also explain why there was no granuloma observed in the experimental groups since it is responsible for down regulation of granuloma formation as pointed out by El-Sayed et al (2016) that the cytokine has been implicated in the up-regulation of adhesion molecule expression of vascular endothelial which aggregates leukocytes that block parasite migration.…”

Antiparasitic effects of selected isoflavones on flatworms

“…To date, the direct in vitro activity of silymarin or individual silymarin´s flavonolignans on trematodes has not been documented. However, there is an increasing number of studies reporting on the effect of silymarin administration alone or in combination with praziquantel on the infections induced by Schistosoma species in vivo (for example : El-Lakkany et al ., 2012 ; El-Sayed et al ., 2016 ; El-Hawary et al ., 2018 ).…”

“…IFN-γ inhibits fibrosis by antagonizing the pro-fibrotic activity of TGF-β1 whereas the TNF-α is proinflammatory cytokine which activation must be tightly controlled because it can lead to the host-tissue damage ( Szekanecz & Koch, 2007 ). The levels of IL-4, TNF-α, TGF-β1 cytokines were significantly increased in S. mansoni infected group and treatment with silymarin alone or combined with praziquantel resulted in a significant decrease in IL-4, TNF-α and TGF-β1 levels and subsequent significant elevation in serum IFN-γ levels ( El-Sayed et al ., 2016 ). Based on the experimental results the treatment with silymarin combined with praziquantel could reduce hepatic fibrosis also by downregulation of profibrotic cytokines due to its immunomodulatory activity on various cell types in murine schistosomiasis.…”

The role of microRNAs in the pathogenesis, grading and treatment of hepatic fibrosis in schistosomiasis

“…These drugs can inhibit HSC activation and reduce collagen and TGF-β production [107, 108]. Both taurine supplementation and combining PZQ with silymarin substantially ameliorate liver fibrosis, likely by downregulating relevant cytokines or chemokines and reducing the endoplasmic reticular stress response [109, 110]. Mesenchymal stem cell therapy can significantly improve and reverse fibrosis in liver tissues of S. mansoni -infected mice [111].…”