Rabeprazole inhibits several functions of Entamoeba histolytica related with its virulence
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PROTOZOOLOGY - ORIGINAL PAPER
Rabeprazole inhibits several functions of Entamoeba histolytica related with its virulence Yoalli Martínez-Pérez 1,2 & Mario Nequiz-Avendaño 2 & Itzhel García-Torres 3 & Marco E. Gudiño-Zayas 2 & Gabriel López-Velázquez 3 & Sergio Enríquez-Flores 3 & Edith Mendoza 2 & Emma Saavedra 4 & Ruy Pérez-Tamayo 2 & Gloria León-Avila 1 & Alfonso Olivos-García 2 Received: 18 May 2020 / Accepted: 26 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Amoebiasis is a human parasitic disease caused by Entamoeba histolytica. The parasite can invade the large intestine and other organs such as liver; resistance to the host tissue oxygen is a condition for parasite invasion and survival. Thioredoxin reductase of E. histolytica (EhTrxR) is a critical enzyme mainly involved in maintaining reduced the redox system and detoxifying the intracellular oxygen; therefore, it is necessary for E. histolytica survival under both aerobic in vitro and in vivo conditions. In the present work, it is reported that rabeprazole (Rb), a drug widely used to treat heartburn, was able to inhibit the EhTrxR recombinant enzyme. Moreover, Rb affected amoebic proliferation and several functions required for parasite virulence such as cytotoxicity, oxygen reduction to hydrogen peroxide, erythrophagocytosis, proteolysis, and oxygen and complement resistances. In addition, amoebic pre-incubation with sublethal Rb concentration (600 μM) promoted amoebic death during early liver infection in hamsters. Despite the high Rb concentration used to inhibit amoebic virulence, the wide E. histolytica pathogenicrelated functions affected by Rb strongly suggest that its molecular structure can be used as scaffold to design new antiamoebic compounds with lower IC50 values. Keywords Entamoeba histolytica . Reactive oxygen species . Thioredoxin reductase . Amoebic virulence . Liver abscess
Introduction In memoriam of Alfonso Olivos-García. May 26th, 2020. Handling Editor: Julia Walochnik Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00436-020-06868-0) contains supplementary material, which is available to authorized users. * Yoalli Martínez-Pérez [email protected] 1
Departamento de Zoología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N. Col. Casco de Santo Tomás, Ciudad de México 11340, México
2
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, México
3
Grupo de Investigación en Biomoléculas y Salud Infantil, Laboratorio de EIMyT, Instituto Nacional de Pediatría, Ciudad de México 04530, México
4
Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, México
Entamoeba histolytica is a unicellular parasite that causes amoebic colitis and extraintestinal amoebiasis in liver, lung, heart, or brain (Lohia 2003). This parasite is responsible for 100,000 deaths per year worldwide
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