Effects of iron chelating agent on Schistosoma mansoni infected murine model

Biomed Pharmacother. 2019 Jan:109:28-38. doi: 10.1016/j.biopha.2018.10.036. Epub 2018 Nov 2.

Abstract

Schistosomiasis is one of the major health problems in many tropical and developing countries. Infection takes place once cerceriae penetrate human skin, then it changed into schistosomules. The schistosomules takes iron in the form of heme from host's haemoglobin, ferritin and transferrin. Iron is a vital element not only for growth and sexual maturity of schistosomules to adults but also for oogenesis. Since the trapped eggs are the pathological causative agent for most of pathogenesis and complications, the current work was designed to study the effects of early deprivation of schistosomules from iron in the host (in vivo) by chelating it with deferoxamine (DFO). The iron chelation has effects on growth, maturity and egg deposition, as well as it has ameliorative effects on liver pathology such as hepatic fibrosis. Mice were classified into four groups, normal control, DFO treated only, Schistosoma mansoni (S. mansoni) infected DFO untreated and S. mansoni infected DFO treated. The infected DFO treated mice showed significant reduction in fecal egg excretion with increased percentage of dead eggs and this was accompanied with a significant reduction of both total worm burden and hepatic egg load and increased dead egg percentage compared to the infected DFO untreated group. There was also a significant reduction in both serum and hepatic tissue ferritin concentrations in the infected DFO treated mice in comparison to the infected DFO untreated group. Additionally, a significant decrease in number and size of granulomas with subsequent improvement of liver fibrosis was recorded in the infected DFO treated group. This immunopathology was also associated with significant up regulation of Interlukine12 (IL12), Interferon gamma (IFN γ) and significant down regulation in interleukin4 (IL4), interleukin10 (IL10) in both serum and hepatic tissue in the infected DFO treated compared to other groups. Entirely, DFO succeeded in diminishing the growth, maturity and fecundity of S. mansoni with a subsequent improvement of hepatic pathology. As a result of the above findings, it can be concluded that DFO could be considered as a useful treatment against schistosomal infection.

Keywords: Cytokines; Heme; Histopathology; Iron chelation (deferoxamine); Schistosoma mansoni.

MeSH terms

  • Animals
  • Deferoxamine / pharmacology*
  • Disease Models, Animal
  • Granuloma / drug therapy
  • Granuloma / parasitology
  • Iron Chelating Agents / pharmacology*
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / parasitology
  • Liver Diseases / drug therapy
  • Liver Diseases / parasitology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Schistosoma mansoni / drug effects*
  • Schistosomiasis mansoni / drug therapy*

Substances

  • Iron Chelating Agents
  • Deferoxamine