Peroxynitrite and Peroxiredoxin in the Pathogenesis of Experimental Amebic Liver Abscess

Abstract

The molecular mechanisms by which Entamoeba histolytica causes amebic liver abscess (ALA) are still not fully understood. Amebic mechanisms of adherence and cytotoxic activity are pivotal for amebic survival but apparently do not directly cause liver abscess. Abundant evidence indicates that chronic inflammation (resulting from an inadequate immune response) is probably the main cause of ALA. Reports referring to inflammatory mechanisms of liver damage mention a repertoire of toxic molecules by the immune response (especially nitric oxide and reactive oxygen intermediates) and cytotoxic substances released by neutrophils and macrophages after being lysed by amoebas (e.g., defensins, complement, and proteases). Nevertheless, recent evidence downplays these mechanisms in abscess formation and emphasizes the importance of peroxynitrite (ONOO−). It seems that the defense mechanism of amoebas against ONOO−, namely, the amebic thioredoxin system (including peroxiredoxin), is superior to that of mammals. The aim of the present text is to define the importance of ONOO− as the main agent of liver abscess formation during amebic invasion, and to explain the superior capacity of amoebas to defend themselves against this toxic agent through the peroxiredoxin and thioredoxin system.

Differential expression of pathogenic genes of Entamoeba histolytica vs E. dispar in a model of infection using human liver tissue explants

“…dispar infection. These enzymes have the capacity to protect parasites under certain conditions of oxidative and thermal stress [ 52 – 54 ], which indicates that E . dispar cannot adapt and survive in the hostile environment of liver parenchyma.…”

“…Several strategies have been developed by prokaryotic and eukaryotic organisms to protect themselves against oxygen toxicity, employing enzymes that destroyperoxides and superoxide anions, as well as small molecules as antioxidants (e.g., vitamins E and C), and thiol groups as scavengers of transient free radicals. They possess several enzymes to defend from oxidative stress, such as peroxiredoxin (Prx), superoxide dismutase, flavoprotein A, ferredoxin, thioredoxin (Trx), and Trx reductase, capable of catalyzing the conversion of superoxide to O 2 and hydrogen peroxide (H 2 O 2 ) [ 53 , 54 ], and a flavin reductase (NADPH: flavin oxidoreductase) also able to reduce O 2 to H 2 O 2 [ 55 ].…”

Nitric oxide maintains cell survival of Trichomonas vaginalis upon iron depletion

“…The up-regulation of NO in parallel with elevated antioxidant capacity suggests that NO signaling might be critical for iron-deficient T. vaginalis [ 37 ]. NO serves as a regulator to protect the cells from iron shortage-mediated damages [ 38 ].…”

The effect of IFN-γ and TGF-β in the functional activity of mononuclear cells in the presence of Entamoeba histolytica

“…Phagocytosis and microbicidal activity by phagocytes, with the production of active oxygen metabolites such as free radicals, make up an important defense mechanism against a number of bacterial [ 8 , 10 , 12 ], fungal [ 30 ] and protozoal infections [ 9 , 26 , 31 ]. Cytokines such as IFN-γ primarily act on monocytes/macrophages by activating their phagocytic and microbicidal abilities [ 32 ].…”