Development of a Novel Ex-vivo 3D Model to Screen Amoebicidal Activity on Infected Tissue

Area of Science:

• Parasitology
• Drug Discovery
• Toxicology

Background:

• Amoebiasis, caused by Entamoeba histolytica, is a significant cause of mortality.
• Drug resistance necessitates novel treatment strategies and screening methods for amoebiasis.

Purpose of the Study:

• To implement and validate a 3D ex vivo model using precision-cut hamster intestine and liver slices.
• To evaluate the efficacy and toxicity of novel amoebicidal compounds against E. histolytica.

Main Methods:

• Infection of ex vivo hamster intestine and liver slices with virulent E. histolytica trophozoites.
• Treatment of infected tissues with chemically synthesized compounds (T-001, T-011, T-016) and metronidazole.
• Histological examination to assess tissue damage and amoebae presence.
• Evaluation of compound-induced cytotoxicity in liver slices.

Main Results:

• The 3D ex vivo model successfully replicated intestinal ulcerations and liver microabscesses characteristic of amoebiasis.
• Compounds T-001 and T-016 demonstrated amoebicidal activity, reducing trophozoite counts and causing amoeba disintegration.
• Compound T-011 showed efficacy but also induced cytotoxicity in liver slices.
• Metronidazole served as a positive control, exhibiting similar amoebicidal effects.

Conclusions:

• Ex vivo precision-cut tissue slice cultures provide a reliable 3D model for evaluating novel amoebicidal compounds.
• This model allows for simultaneous assessment of drug efficacy and toxicity, potentially reducing animal use in research.
• The findings support the development of new therapeutic agents for amoebiasis.