Effect of mast cell stabilization on angiogenesis in primary and secondary experimental Trichinella spiralis infection

Marwa A El-Dardiry,Asmaa A Abdel-Aal,Amany A Abdel-Aal,Magda S A Abdeltawab,Shady E Anis,Bahaa-Eldin A Khaled,Manal Badawi,Abeer S Al-Antably,Mona El-Sherbini,Marwa A Hassan

doi:10.1186/s13071-021-05075-9

Abstract

BackgroundMast cells are known to affect the primary and secondary immune responses against parasites, and this effect is partially mediated through the release of pro-angiogenic mediators. The aim of this study was to explore the effect of the mast cell stabilizer (MCS), ketotifen, with and without albendazole, an anti-parasitic prescription medicine, on the inflammatory response against Trichinella spiralis, with the overall aim to investigate its effect on angiogenesis accompanying nurse cell formation.MethodsThe effect of ketotifen and albendazole was explored in eight groups of female BALB/c mice. Four groups were sensitized with a small dose of T. spiralis larvae. The drug regimen was then applied to both sensitized (challenged) and non-sensitized mice. The parasite load was assessed by histopathological examination of the small intestine and muscle tissue, and angiogenesis was assessed by immunohistochemistry to determine the expression of vascular endothelial growth factor (VEGF).ResultsSensitized mice showed a significantly lower parasite load and a more pronounced inflammatory response than mice receiving a single infective dose of T. spiralis larvae. All treated groups showed a significant reduction in parasite count compared to the control groups (groups IAa and IBa), reaching approximately an 98.8% reduction in adult parasite count in the sensitized group treated with albendazole (groups IIAb and IIBb). MCS significantly decreased the parasite count during both the intestinal or muscular phases, reduced tissue inflammation, and decreased local VEGF expression, both in the non-sensitized and sensitized groups.ConclusionSensitization with a low dose of T. spiralis larvae was found to confer a partial protective immunity against re-infection and to positively affect the study outcomes, thus underlining the importance of vaccination, but after extensive studies. The anti-angiogenic effect of MCS protects against larval encystation during the muscle phase. The anti-angiogenic potential of albendazole suggests that the action of this anti-helminthic during trichinellosis is not confined to structural damage to the parasite cuticle but includes an effect on host immunopathological response.Graphical

Highlights

Mast cells are known to affect the primary and secondary immune responses against parasites, and this effect is partially mediated through the release of pro-angiogenic mediators
The present study explores the effect of the mast cell stabilizer (MCS) ketotifen on the inflammatory response during the intestinal and muscular phases related to both primary and secondary experimental T. spiralis infection
MCS reduced intestinal worm burden more efficiently in sensitized mice than in non‐sensitized mice, while in the muscle phase, it was more effective in reducing the larval load in non‐sensitized mice In non-sensitized mice receiving MCS only, the adult intestinal count was 56.7 ± 6.61/100 ml intestinal fluid, which is a reduction of 25.39% compared to the control non-sensitized group

Summary

Introduction

Mast cells are known to affect the primary and secondary immune responses against parasites, and this effect is partially mediated through the release of pro-angiogenic mediators. Trichinella infection in all affected hosts, including humans, passes through two phases: the intestinal phase and the muscular phase Subsequent complications, such as cardiac or neurological problems, result from the aggressive pathogenesis caused by the larval stages and may lead to a fatal outcome [10, 20]. Benzimidazoles, such as albendazole and mebendazole, are the most common anti-helminthics used in the management of T. spiralis infection. In addition to its anti-helminthic activity, albendazole has been found to have an anti-angiogenic effect in both cancerous and non-cancerous models of angiogenesis These effects are mediated, partially, by through a decrease in the level of vascular endothelial growth factor (VEGF) and the downregulation of VEGF-2 receptors [22]. VEGF plays an important role in the pathological process of angiogenesis during inflammation or cancer [26]

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