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Auranofin attenuates Schistosoma mansoni egg-induced liver granuloma and fibrosis in mice

Published online by Cambridge University Press:  06 December 2023

A.F. Atia
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
N.M. Abou-Hussien
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
D.M. Sweed
Affiliation:
Pathology Department, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt
E. Sweed*
Affiliation:
Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
N.A. Abo-khalil
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
*
Corresponding author: E. Sweed; Email: eman.sweed@med.menofia.edu.eg

Abstract

Schistosomiasis is a serious tropical disease. Despite extensive research into the etiology of liver fibrosis, effective therapeutic options remain limited. This study aims to assess the effectiveness of auranofin in treating hepatic granuloma and fibrogenesis produced by Schistosoma (S.) mansoni eggs. Auranofin is a gold complex that contains thioglucose tetraacetate and triethylphosphine. Eighty BALB/c male mice were divided into four groups (n=20/group): negative control (GI), positive control (GII), and early (GIII) and late (GIV) treatment groups with oral auranofin according to beginning of treatment 4th week and 6th week post-infection. Mice were infected subcutaneously in a dose of 60±10 cercariae/mouse. Worm counts, egg loads, and oogram patterns were determined. Biochemical, histological, and immunostaining of interleukin-1β (IL-1β), Sirtuin 3 (SIRT3), and smooth muscle actin (SMA) were assessed. GIII showed a significant decrease in the total S. mansoni worm burden and ova/gram in liver tissue (with reduction percent of 63.07% and 78.26%, respectively). Schistosomal oogram patterns, immature and mature ova, also showed a significant decrease. The reduction in granuloma number and size was 40.63% and 48.66%, respectively, in GIII, whereas in GIV, the reduction percent was 76.63% and 67.08%. In addition, the degree of fibrosis was significantly diminished in both treated groups. GIV showed significant reduction in IL-1β and SMA expression and increase in SIRT3 expression. These findings reveal how auranofin suppresses the development of liver fibrosis. Therefore, it is crucial to take another look at auranofin as a prospective medication for the treatment of S. mansoni egg-induced hepatic granuloma and consequent fibrosis.

Type
Research Paper
Copyright
© The Author(s), 2023. Published by Cambridge University Press

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