TY - JOUR
T1 - Rabeprazole inhibits several functions of Entamoeba histolytica related with its virulence
AU - Martínez-Pérez, Yoalli
AU - Nequiz-Avendaño, Mario
AU - García-Torres, Itzhel
AU - Gudiño-Zayas, Marco E.
AU - López-Velázquez, Gabriel
AU - Enríquez-Flores, Sergio
AU - Mendoza, Edith
AU - Saavedra, Emma
AU - Pérez-Tamayo, Ruy
AU - León-Avila, Gloria
AU - Olivos-García, Alfonso
N1 - Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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 pathogenic-related functions affected by Rb strongly suggest that its molecular structure can be used as scaffold to design new antiamoebic compounds with lower IC50 values.
AB - 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 pathogenic-related functions affected by Rb strongly suggest that its molecular structure can be used as scaffold to design new antiamoebic compounds with lower IC50 values.
KW - Amoebic virulence
KW - Entamoeba histolytica
KW - Liver abscess
KW - Reactive oxygen species
KW - Thioredoxin reductase
UR - http://www.scopus.com/inward/record.url?scp=85090133927&partnerID=8YFLogxK
U2 - 10.1007/s00436-020-06868-0
DO - 10.1007/s00436-020-06868-0
M3 - Artículo
C2 - 32886229
AN - SCOPUS:85090133927
SN - 0932-0113
VL - 119
SP - 3491
EP - 3502
JO - Parasitology Research
JF - Parasitology Research
IS - 10
ER -