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Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model

Yasmine Amr Issa1, Samar Nabil El Achy2, Rasha Fadly Mady3

  • 1University of Alexandria, Alexandria Faculty of Medicine, Medical Biochemistry Department, Alexandria, Egypt.

Memorias Do Instituto Oswaldo Cruz
|August 8, 2019
PubMed
Abstract

Insights

Combining praziquantel (PZQ) with CB1 receptor antagonists significantly reversed schistosomiasis-associated liver fibrosis (SSLF) in mice. This novel therapeutic approach offers a promising strategy for treating liver damage caused by Schistosoma mansoni infection.

Area of Science:

  • Hepatology
  • Immunology
  • Parasitology

Background:

  • Schistosomiasis-associated liver fibrosis (SSLF) results from granulomatous inflammation around Schistosoma ova.
  • Praziquantel (PZQ), the current treatment, does not effectively reverse established SSLF.
  • Cannabinoid (CB) receptors are implicated in the pathogenesis of liver fibrosis.

Purpose of the Study:

  • To evaluate the efficacy of CB1 receptor antagonism in ameliorating SSLF.
  • To assess the combined therapeutic effect of PZQ and a CB1 antagonist in a murine model of Schistosoma mansoni infection.

Main Methods:

  • 100 male Swiss albino mice were allocated into five groups: control, infected, PZQ-treated, rimonabant (RIM)-treated, and combined PZQ+RIM treated.
  • Histopathological examination, alpha-1 smooth muscle actin (α-SMA) immunostaining, and CB1 receptor expression analysis via RT-PCR were performed on liver sections.

Main Results:

  • Combined PZQ and RIM treatment (group V) demonstrated the most significant reduction in fibrotic markers and granuloma load.
  • This combination therapy led to significant decreases in CB1 receptor expression, α-SMA-positive cells, hepatic portal fibrosis, and granuloma number (p < 0.001 for all).

Conclusions:

  • Combined treatment with PZQ and CB1 receptor antagonists is highly effective in reversing SSLF.
  • This study is the first to report the successful use of this combined regimen in a Schistosoma mansoni infection model.

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