Synergistic effects of resveratrol (free and inclusion complex) and sulfamethoxazole-trimetropim treatment on pathology, oxidant/antioxidant status and behavior of mice infected with Toxoplasma gondii

Bottari, Nathieli B.; Baldissera, Matheus D.; Tonin, Alexandre A.; Rech, Virgínia Cielo; Alves, Catiane B.; D'Avila, Fernanda; Thomé, Gustavo R.; Guarda, Naiara S.; Moresco, Rafael Noal; Camillo, Giovana; Vogel, Fernanda Silveira Flores; Luchese, Cristiane; Schetinger, Maria Rosa Chitolina; Morsch, Vera Maria; Tochetto, Camila; Fighera, Rafael A.; Nishihira, Vivian Shinobu Kishimoto; Silva, Aleksandro S. Da

doi:10.1016/j.micpath.2016.04.002

Cited by 25 publications

(25 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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). Recently, it has also been considered to be a therapy for congenital toxoplasmosis because of its ability to restore the neurogliogenesis of neural progenitor cells infected by T. gondii (33).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies indicated the potential activity of resveratrol against both promastigotes and amastigotes of Leishmania parasites (20). Moreover, resveratrol has also been shown to reduce oxidative damage and to prevent the behavior changes seen in T. gondii-infected mice when administered together with traditional therapeutic drugs (21)(22)(23). However, the mechanism behind the interactions between the compound, the parasites, and host cells remains unclear.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Chen

Dong

Qin

et al. 2019

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Chen

Dong

Qin

et al. 2019

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Interestingly, Bottari et al reported that the treatment of T. gondii-infected mice with sulfamethoxazole-trimethoprim partly rescued the behavioral changes associated with T. gondii infection, suggesting that the degree of brain inflammation affects these behavioral changes (44). Therefore, to investigate whether the degree of inflammation in each brain region affected the behavioral changes in the infected mice, we examined the correlation between the expression of IFN-␥ and the percentage of time that the mice spent freezing in the fear-conditioning test.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala

et al. 2016

View full text Add to dashboard Cite

cChronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection.T oxoplasma gondii is one of the most successful brain parasites, infecting approximately one-third of the human population (1). T. gondii can persist in brain and muscle throughout the host's life, and chronic infection is asymptomatic in immunocompetent humans (2). However, recent studies have suggested that T. gondii infection is a risk factor for developing mental diseases, such as schizophrenia and depression, as well as human behavior and personality changes and suicide (3, 4). Interestingly, T. gondii infection increases the risk of schizophrenia roughly 2.7 times, which is higher than that for genes associated with schizophrenia (5). Several studies have also suggested that rodents infected with T. gondii exhibit decreased avoidance behavior in response to cat odors, indicating manipulation of the host's behavior by T. gondii to facilitate the parasite's transmission and complete sexual replication in the definitive host (6-11).To date, research on the mechanism(s) underlying behavioral changes following T. gondii infection has been conducted primarily from two points of view. First, the relationship between parasite localization in the brain and behavioral changes has been investigated, with a previous study reporting that T. gondii has no obvious tropism in the brain (12-15). However, another study found that tissue cyst density in amygdalar areas (the medial and basolateral amygdala) is 2-fold higher than that in nonamygdalar areas (9), whereas the presence of tissue cy...

show abstract

“…Resveratrol also inhibits STAT3 signaling pathway [ 14 ], the mTOR signaling [ 15 ], and the hedgehog signaling pathway [ 16 ]. Furthermore, resveratrol reportedly constrains infections caused by multiple pathogens, such as Helicobacter pylori [ 17 ], Staphylococcus aureus [ 18 ] or Toxoplasma gondii [ 19 ]. Interestingly, resveratrol has been demonstrated to exert antiviral effects against various viral infections, including Epstein-Barr virus (EBV) [ 20 , 21 ], enterovirus 71 (EV71) [ 22 ], and herpes simplex virus (HSV) [ 23 ], as well as respiratory viral infections caused by influenza [ 24 ], respiratory syncytial virus (RSV) [ 25 , 26 ], and rhinovirus [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Effective inhibition of MERS-CoV infection by resveratrol

et al. 2017

View full text Add to dashboard Cite

BackgroundMiddle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that causes severe morbidity and mortality. Up to date, there is no approved or licensed vaccine or antiviral medicines can be used to treat MERS-CoV-infected patients. Here, we analyzed the antiviral activities of resveratrol, a natural compound found in grape seeds and skin and in red wine, against MERS-CoV infection.MethodsWe performed MTT and neutral red uptake assays to assess the survival rates of MERS-infected Vero E6 cells. In addition, quantitative PCR, western blotting, and immunofluorescent assays determined the intracellular viral RNA and protein expression. For viral productivity, we utilized plaque assays to confirm the antiviral properties of resveratrol against MERS-CoV.ResultsResveratrol significantly inhibited MERS-CoV infection and prolonged cellular survival after virus infection. We also found that the expression of nucleocapsid (N) protein essential for MERS-CoV replication was decreased after resveratrol treatment. Furthermore, resveratrol down-regulated the apoptosis induced by MERS-CoV in vitro. By consecutive administration of resveratrol, we were able to reduce the concentration of resveratrol while achieving inhibitory effectiveness against MERS-CoV.ConclusionIn this study, we first demonstrated that resveratrol is a potent anti-MERS agent in vitro. We perceive that resveratrol can be a potential antiviral agent against MERS-CoV infection in the near future.

show abstract

Synergistic effects of resveratrol (free and inclusion complex) and sulfamethoxazole-trimetropim treatment on pathology, oxidant/antioxidant status and behavior of mice infected with Toxoplasma gondii

Cited by 25 publications

References 38 publications

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

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

Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala

Effective inhibition of MERS-CoV infection by resveratrol

Contact Info

Product

Resources

About