Curcumin Attenuates the Pathogenicity of Entamoeba histolytica by Regulating the Expression of Virulence Factors in an Ex-Vivo Model Infection.

Itzia Azucena Rangel-Castañeda,Nancy Elena Guzmán-Delgado,Sirenia González-Pozos,José Manuel Hernández-Hernández,Pilar Carranza-Rosales,Armando Pérez-Rangel,Araceli Castillo-Romero

doi:10.3390/pathogens8030127

Itzia Azucena Rangel-Castañeda, Nancy Elena Guzmán-Delgado + Show 5 more

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https://doi.org/10.3390/pathogens8030127

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Abstract

Infection with the enteric protozoan Entamoeba histolytica is still a serious public health problem, especially in developing countries. Amoebic liver abscess (ALA) is the most common extraintestinal manifestation of the amoebiasis, and it can lead to serious and potentially life-threatening complications in some people. ALA can be cured by metronidazole (MTZ); however, because it has poor activity against luminal trophozoites, 40–60% of treated patients get repeated episodes of invasive disease and require repeated treatments that can induce resistance to MTZ, this may emerge as an important public health problem. Anti-virulence strategies that impair the virulence of pathogens are one of the novel approaches to solving the problem. In this study, we found that low doses of curcumin (10 and 50 μM) attenuate the virulence of E. histolytica without affecting trophozoites growth or triggering liver injury. Curcumin (CUR) decreases the expression of genes associated with E. histolytica virulence (gal/galnac lectin, ehcp1, ehcp5, and amoebapore), and is correlated with significantly lower amoebic invasion. In addition, oxidative stress is critically involved in the etiopathology of amoebic liver abscess; our results show no changes in mRNA expression levels of superoxide dismutase (SOD) and catalase (CAT) after E. histolytica infection, with or without CUR. This study provides clear evidence that curcumin could be an anti-virulence agent against E. histolytica, and makes it an attractive potential starting point for effective treatments that reduce downstream amoebic liver abscess.

Highlights

The protozoa Entamoeba histolytica causes several clinical syndromes, ranging from dysentery of acute colitis to amoebic liver abscess (ALA), and other extra-intestinal diseases [1,2,3]
We found that CUR at low concentrations (10 and 50 μM) displayed direct activity against E. histolytica, inhibiting the virulence factors expression and pathogenicity of this parasite; histopathological analysis and microscopy images revealed that the presence of CUR during the infection prevents liver amoebic invasion
E. histolytica has been associated with around 100 million cases of amoebic dysentery, colitis, and Amoebic liver abscess (ALA) that lead to almost 50,000 deaths each year [32,33]

Summary

Introduction

The protozoa Entamoeba histolytica causes several clinical syndromes, ranging from dysentery of acute colitis to amoebic liver abscess (ALA), and other extra-intestinal diseases [1,2,3]. Diverse in vitro and in vivo studies have demonstrated that multiple molecules from E. histolytica are involved directly. The complete sequence of morphologic events during ALA formation has been studied in vivo and in vitro models. The use of precision-cut hamster liver slices has brought remarkable contributions, from the lodgment of amebas in the hepatic sinusoids to the development of extensive liver necrosis. The ex vivo models have contributed to use reduction of experimental animals [10,11,12]

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