Dehydroepiandrosterone Effect on Toxoplasma gondii: Molecular Mechanisms Associated to Parasite Death

Muñiz-Hernández, Saé; Luna-Nophal, Angélica; León, Carmen T Gómez-De; Domínguez-Ramírez, Lenin; Patrón-Soberano, Olga Araceli; Nava-Castro, Karen Elizabeth; Ostoa‐Saloma, Pedro; Morales‐Montor, Jorge

doi:10.3390/microorganisms9030513

Cited by 5 publications

(7 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The combination of 17β-estradiol and progesterone significantly reduced Toxoplasma gondii replication and the percentage of infected neurons; this may be due to the major expression of classical estrogen receptors [ 39 ], E2 plus progesterone modulating the viability of extracellular parasites and the passive invasion to neurons. This result is similar to host cells infected with tachyzoites treated with dehydroepiandrosterone (DHEA) [ 13 , 56 , 57 ].…”

Section: Discussionsupporting

confidence: 69%

“…The combination of progesterone and Mif exerted a lesser effect on Toxoplasma infected neurons compared with progesterone alone. One explanation could be a change in progesterone membrane receptors as well as in their affinity [ 13 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…The administration of testosterone to females reduced parasite burdens and lesions [ 12 ]. Furthermore, dehydroepiandrosterone (DHEA) can reduce the passive invasion and viability of extracellular Toxoplasma tachyzoites in vitro [ 13 ]. These results suggest the participation of an essential steroid hormone in Toxoplasma gondii infection.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of 17β-Estradiol, Progesterone, and Tamoxifen on Neurons Infected with Toxoplasma gondii In Vitro

et al. 2021

View full text Add to dashboard Cite

Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis, which produces damage in the central nervous system (CNS). Toxoplasma–CNS interaction is critical for the development of disease symptoms. T. gondii can form cysts in the CNS; however, neurons are more resistant to this infection than astrocytes. The probable mechanism for neuron resistance is a permanent state of neurons in the interface, avoiding the replication of intracellular parasites. Steroids regulate the formation of Toxoplasma cysts in mice brains. 17β-estradiol and progesterone also participate in the control of Toxoplasma infection in glial cells in vitro. The aim of this study was to evaluate the effects of 17β-estradiol, progesterone, and their specific agonists–antagonists on Toxoplasma infection in neurons in vitro. Neurons cultured were pretreated for 48 h with 17β-estradiol or progesterone at 10, 20, 40, 80, or 160 nM/mL or tamoxifen 1 μM/mL plus 17β-estradiol at 10, 20, 40, 80, and 160 nM/mL. In other conditions, the neurons were pretreated during 48 h with 4,4′,4″-(4-propyl-[1H] pyrozole-1,3,5-triyl) trisphenol or 23-bis(4-hydroxyphenyl) propionitrile at 1 nM/mL, and mifepristone 1 µM/mL plus progesterone at 10, 20, 40, 80, and 160 nM/mL. Neurons were infected with 5000 tachyzoites of the T. gondii strain RH. The effect of 17β estradiol, progesterone, their agonists, or antagonists on Toxoplasma infection in neurons was evaluated at 24 and 48 h by immunocytochemistry. T. gondii replication was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. 17β-Estradiol alone or plus tamoxifen reduced infected neurons (50%) compared to the control at 48 h. Progesterone plus estradiol decreased the number of intracellular parasites at 48 h of treatment compared to the control (p < 0.001). 4,4′,4″-(4-propyl-[1H] pyrozole-1,3,5-triyl) trisphenol and 23-bis(4-hydroxyphenyl) propionitrile reduced infected neurons at 48 h of treatment significantly compared to the control (p < 0.05 and p < 0.001, respectively). The Toxoplasma infection process was decreased by the effect of 17β-estradiol alone or combined with tamoxifen or progesterone in neurons in vitro. These results suggest the essential participation of progesterone and estradiol and their classical receptors in the regulation of T. gondii neuron infection.

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of 17β-Estradiol, Progesterone, and Tamoxifen on Neurons Infected with Toxoplasma gondii In Vitro

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Next, the pretreated extracellular parasites were mixed thoroughly, 100 µl of the mixture was added into 6-well plates containing coverslips with confluent hTERT cells supplemented with 2 ml of fresh medium and allowed to infect the host cells for 1 h, followed by washing away the extracellular parasites using sterilized 1× PBS, performed 3 times, fixed with 100% ethanol, and incubated overnight at 4°C. The next day, the ethanol was taken out followed by three washes with 1× PBS, then stained with hematoxylin for 10 min, washed with 50% ethanol-H 2 O for 5 min, then stained with Eosin for 5 min, and washed with 50% ethanol-H 2 O ( León-Nava et al., 2016 ; Muñiz-Hernández et al., 2021 ). Plates containing stained parasites were visualized for parasitophorous vacuole (PV) formation using the Zeiss 100 phase-contrast fluorescence microscope coupled with an Amscope camera.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Toxoplasma gondii Growth by Dihydroquinine and Its Mechanisms of Action

Huffman

Ayariga

Napier

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Toxoplasma gondii is a zoonotic parasite that infects the brain of humans and causes cerebral toxoplasmosis. The recommended drugs for the treatment or prophylaxis of toxoplasmosis are pyrimethamine (PY) and sulfadiazine (SZ), which have serious side effects. Other drugs available for toxoplasmosis are poorly tolerated. Dihydroquinine (DHQ) is a compound closely related to quinine-based drugs that have been shown to inhibit Plasmodium falciparum and Plasmodium berghei in addition to its anti-arrhythmia properties. However, little is known about the effect of DHQ in T. gondii growth and its mechanism of action in vitro. In this study, we report the anti-Toxoplasma and anti-invasion properties of DHQ. DHQ significantly inhibited T. gondii tachyzoite growth with IC50s values of 0.63, 0.67, and 0.00137 µM at 24, 48, and 72 h, respectively. Under similar conditions, SZ and PY, considered as the gold standard drugs for the treatment of toxoplasmosis, had IC50s values of 1.29, 1.55, and 0.95 and 3.19, 3.52, and 2.42 µM, respectively. The rapid dose-dependent inhibition of T. gondii tachyzoites by DHQ compared to the standard drugs (SZ and PY) indicates that DHQ has high selective parasiticidal effects against tachyzoite proliferation. Remarkably, DHQ had an excellent selectivity index (SI) of 149- and 357-fold compared to 24- and 143-fold for PY and SZ, respectively, using fibroblast cells. In addition, DHQ disrupted T. gondii tachyzoite mitochondrial membrane potential and adenosine triphosphate (ATP) production and elicited high reactive oxygen species (ROS) generation. Taking all these findings together, DHQ promises to be an effective and safe lead for the treatment of toxoplasmosis.

show abstract

“…Despite being a hormone, it has proven to be a highly effective antiparasite medication. In vitro, low levels of DHEA prevent Entamoeba trophozoites from proliferating, adhering to one another, and moving about, whereas high levels drive the parasite's lysis [9]. DHEA possesses toxoplasmicidal actions on extracellular tachyzoites.…”

Section: Introductionmentioning

confidence: 99%

Role of IL-1β, Prolactin and DHEA in men Patients Infected with Toxoplasmosis

Ali faieq,

Al-Hadraawy

2024

BIO Web Conf.

View full text Add to dashboard Cite

Toxoplasma gondii has a worldwide distribution and it is one of the most prevalent infectious agents in Iraq, as it is found in various mammals, fish, and terrestrial and water birds. Cats are the only definitive host for the parasite that throws the infective phase into the environment. The primary aim of this study was to determine the serum levels of IL-1β, prolactin, Dehydroepiandrosterone (DHEA) in patients and healthy group.The study was conducted on 260 Males suspected of Toxoplasmosis ages ranging from 20-50 years old. All these cases were examined by measuring Toxo IgG serum levels, who attended AL-Hakeem hospital, and (30) healthy males as the control group, collected randomly from AL-Najaf province, these samples were collected from March 2023 to August 2023. Any patient was using the drug or undergoing disease removal from the current study. The current study revealed that the concentration of IL-1β inpatients infected with Toxoplasmosis were significant increase (P<0.05) compared to the control group, but the concentration of (prolactin) in patients infected with toxoplasmosis were significant decrease (P<0.05) is compared to the control group. Also, it revealed that the DHEA levels were elevated but non significantly in samples infected with Toxoplasmosis compared to the control group. The current study has concluded that infection with Toxoplasmosis may be a risk factor. A chronic T. gondii infection is associated with variations in levels of serum prolactin and these variations may influence the immune system by IL-1β increase the susceptibility to Toxoplasmosis infection.

show abstract

Dehydroepiandrosterone Effect on Toxoplasma gondii: Molecular Mechanisms Associated to Parasite Death

Cited by 5 publications

References 48 publications

Effect of 17β-Estradiol, Progesterone, and Tamoxifen on Neurons Infected with Toxoplasma gondii In Vitro

Effect of 17β-Estradiol, Progesterone, and Tamoxifen on Neurons Infected with Toxoplasma gondii In Vitro

Inhibition of Toxoplasma gondii Growth by Dihydroquinine and Its Mechanisms of Action

Role of IL-1β, Prolactin and DHEA in men Patients Infected with Toxoplasmosis

Contact Info

Product

Resources

About