Antioxidant defense of Nrf2vspro-inflammatory system of NF-κB during the amoebic liver infection in hamster

Abstract

Entamoeba histolytica is the causative agent of amoebic liver abscess (ALA), which course with an uncontrolled inflammation and nitro-oxidative stresses, although it is well known that amoeba has an effective defence mechanisms against this toxic environment, the underlying molecular factors responsible for progression of tissue damage remain largely unknown. The purpose of the present study was to determine during the acute stage of ALA in hamsters, the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-kappa B (NF-κB), which are activated in response to oxidative stress. From 12 h post-infection the ALA was visible, haematoxylin-eosin and Masson's trichrome stains were consistent with these observations, and alanine aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase serum activities were increased too. At 48 h after infection, liver glycogen content was significantly reduced. Western blot analyses showed that 4-Hydroxy-2-nonenal peaked at 12 h, while glycogen synthase kinase-3β, cleaved caspase-3, pNF-κB, interleukin-1β and tumour necrosis factor-α were overexpressed from 12 to 48 h post-infection. Otherwise, Nrf2 and superoxide dismutase-1, decreased at 48 h and catalase declined at 36 and 48 h. Furthermore, heme oxygenase-1 was increased at 12 and 24 h and decreased to normal levels at 36 and 48 h. These findings suggest for the first time that the host antioxidant system of Nrf2 is influenced during ALA.

Adrenergic regulation during acute hepatic infection withEntamoeba histolyticain the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB

“…Our results show that amebic liver lesions are visible at 12 h, which was consistent with increased serum enzyme activity for ALT and γ-GTP; these results agreed with previous findings [ 1 ]. ALT is an enzyme located in the cytosol of hepatocytes [ 49 ], and in the present study, we observed slightly elevated levels, possibility because serum evaluation was performed at 12 h post-liver infection (ALA group).…”

“…It is known that at 12 h of amebic liver infection, the amount of polymorphonuclear leukocytes infiltrated and the lesion size are increased, forming microabscesses [ 63 ]. In addition, in a previous study [ 1 ], we reported that at this time, the increase in oxidative stress is greatest and the NF-κB pro-inflammatory pathway is activated. Moreover, the effect of the SNS and PNS during the early and late stages of amebic infection has also begun to be studied [ 3 , 42 , 51 ], but there is little knowledge on their participation and their relationship with the oxidative stress that is generated during the first hours of amebic infection.…”

“…Additionally, our present results showed that chemical denervation did not increased protein expression of Nrf2 and HO-1, as compared to healthy controls. Recently, our group reported that during acute liver infection by E. histolytica, the Nrf2 pathway was inactivated, which may favor overactivation of NF-κB and the progression of liver damage [ 1 ]. Therefore, our results suggest that chemical sympathectomy reduced ALA progression as a result of a compensatory response by activating intrinsic autoregulatory mechanisms controlled by the PNS, although more studies are needed to confirm this hypothesis.…”

“…Oxidative stress is commonly associated with several liver diseases including ALA [ 1 , 55 ]. Therefore, we measured intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) in liver samples using an EnzyChrom TM GSH/GSSG Assay Kit, (Bioassay Systems, Hayward, CA, USA).…”

“…Moreover, recently we demonstrated that during the acute phase of ALA, the pro-inflammatory system of NF-κB is activated while the host antioxidant system of Nrf2 is decreased, inducing uncontrolled inflammation and oxidative stress. This contributes to increased disease severity [ 1 ]. Nrf2 is a transcriptional factor that controls the antioxidant defense system through induction of several stress response proteins, such as HO-1 [ 37 ].…”