Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica

Abstract

Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound) on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis.

Direct and Indirect Inhibition Effects of Resveratrol against Toxoplasma gondii Tachyzoites In Vitro

“…The polyphenol resveratrol has been widely studied for its potential for the treatment of multiple different diseases. The biological features of this compound enable it to act against several medically important protozoa, including leishmania and amoeba (12,20). It has been demonstrated that resveratrol has antitoxoplasma activity as well as a synergistic therapeutic effect that is able to alleviate liver damage, regulate oxidant and antioxidant levels, and prevent the alteration of the behavior of infected mice in vivo as a result of its antioxidant and anti-inflammatory functions (21).…”

“…Resveratrol (3,4=,5-trihydroxystilbene) is a polyphenol naturally found in plants and fruits, including black grapes, mulberries, and also peanuts (12)(13)(14)(15). Considered a powerful antioxidant, this biological compound has been reported to have antibacterial, antifungal, anticancer, and antiparasite activities (12,(15)(16)(17)(18). Furthermore, it is well tolerated at a relatively high dose (19,20).…”

Cell death offers exceptional cellular and molecular windows for pharmacological interventions in protozoan parasites

“…Amoebapore and cysteine proteases may serve to directly activate caspase 3. Relatedly, resveratrol treated -E. histolytica trophozoites leads to activated calpain, phosphatidylserine externalization and DNA fragmentation (apoptosis-like death) [61]. Interestingly, for malaria parasites of the genus Plasmodium that is transmitted through an infected mosquito bite, apoptosis of both the Plasmodium parasite (limiting the infection load to prevent vector death before sporozoite maturation) and cells in the mosquito vector (changing in resource partitioning via follicular epithelial cell death, thus fecundity reduction) work together to augment the probability of consecutive Plasmodium transmission.…”

Antiamoebic Activity of Adenophyllum aurantium (L.) Strother and Its Effect on the Actin Cytoskeleton of Entamoeba histolytica

“…Important processes in the pathogenicity of E. histolytica such as fibronectin adhesion and erythrophagocytosis were inhibited; these activities strongly depend on a functional actin cytoskeleton. Furthermore, the reduction in the number of vacuoles by Aa EaR as observed for other antiamoebics ( Velázquez-Domínguez et al, 2013 ; Pais-Morales et al, 2016 ) implies that vesicular traffic might have been decreased or abolished. Vesicular traffic is a highly specialized function, and in E. histolytica , it is closely synchronized with the actin cytoskeleton organization.…”