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

Abstract

Toxoplasma gondii is one of the most widespread obligatory parasitic protozoa and infects nearly all warm-blooded animals, leading to toxoplasmosis. The therapeutic drugs currently administered, like the combination of pyrimethamine and sulfadiazine, show high rates of toxic side effects, and drug resistance is encountered in some cases. Resveratrol is a natural plant extract with multiple functions, such as antibacterial, anticancer, and antiparasite activities. In this study, we evaluated the inhibitory effects of resveratrol on tachyzoites of the Toxoplasma gondii RH strain extracellularly and intracellularly. We demonstrate that resveratrol possesses direct antitoxoplasma activity by reducing the population of extracellularly grown tachyzoites, probably by disturbing the redox homeostasis of the parasites. Moreover, resveratrol was also able to release the burden of cellular stress, promote apoptosis, and maintain the autophagic status of macrophages, which turned out to be regulated by intracellular parasites, thereby functioning indirectly in eliminating T. gondii. In conclusion, resveratrol has both direct and indirect antitoxoplasma effects against RH tachyzoites and may possess the potential to be further evaluated and employed for toxoplasmosis treatment.

Resveratrol induces H2A.X phosphorylation and H4K16 de-acetylation inToxoplasma gondii

“…1) with an IC 50 value of 53 +/-4 M. This result agrees with those observed by Chen et al, [14], in which a 50 M of RSV blocked T. gondii intracellular growth. When intracellular tachyzoites were grown for 3 hours under normal conditions and were then treated for 96 hours with different doses of RSV, the maximum dose of 20 M only reduced a 50% the tachyzoite growth rate (Fig.…”

“…Interestingly, RSV also enhances the phosphorylation of SQE motif on T. gondii H2A.X, suggesting a link between the drugs with DNA damage and/or DNA replication stress. Our results add new evidence of putative effect of the multi-target drug RSV in addition to the redox homeostasis alteration suggested recently [14]. Fig 3).…”

“…Toxicity assay on hTERT monolayer and on tachyzoite growth RSV has already demonstrated its anti-T. gondii effect in vitro in two recent works [14,15]. In order to confirm these results in our study model, uninfected or infected hTERT host cell was incubated with different doses of RSV and in two incubation periods (24 and 96 hours).…”

“…In in vivo assays, it was shown that oral administration of RSV during acute T. gondii infection in mice would confer protection and survival [12] as well as moderate tissue inflammation and reduction of parasite replication [13]. Chen et al, [14] observed that incubation of extracellular tachyzoites with RSV during 24 hours affected their viability, probably by disturbing the redox homeostasis of the parasites. Of note, in addition to fork collapse, DNA can be damaged by oxidation.…”

Transcriptional changes in Toxoplasma gondii in response to treatment with monensin

“…Regarding humans, the first-line therapy for T. gondii infection is a combination of pyrimethamine and sulfadiazine. However, this regimen has some limitations because these drugs must be taken for a long duration, often cause side effects, and are incapable of eliminating the latent infection [11]. These drawbacks pose a major obstacle in conventional chemotherapy of toxoplasmosis in humans.…”