Search Results (38)

Toxoplasma gondii, an obligate intracellular protozoan parasite infecting nucleated cells of warm-blooded vertebrates, causes severe complications in immunocompromised hosts. Current therapies remain limited by suboptimal efficacy and toxicity, necessitating novel anti-toxoplasmic agents. Piceatannol (PIC), a natural stilbenoid, demonstrates multifaceted bioactivity including antimicrobial and anti-parasitic effects, suggesting therapeutic potential against T. gondii. Our previous study revealed PIC’s potent anti-parasitic activity, selectively inhibiting T. gondii proliferation and altering parasite morphology without host cytotoxicity. In this study, mechanistic analyses indicated that PIC disrupts mitochondrial integrity in tachyzoites, reducing mitochondrial membrane potential and ATP production while elevating ROS levels. Transcriptomic profiling identified significant suppression of oxidative phosphorylation-related genes, consistent with mitochondrial dysfunction. These findings establish PIC as a promising candidate targeting T. gondii through the mechanism of mitochondrial impairment. Full article

Depressive disorder during pregnancy is a common condition, affecting approximately 10–15% of pregnant women, and is associated with adverse pregnancy outcomes such as inadequate prenatal care, substance abuse, and fetal growth restriction. Beyond neurotransmitter disturbances, increasing evidence suggests that infectious agents may play a role in the pathophysiology of depression through immune system modulation. Toxoplasma gondii infection has been linked to various mental disorders in the general population, including depression and anxiety. This study aimed to investigate whether depressive disorder during pregnancy is associated with chronic T. gondii infection by analyzing cytokine levels involved in inflammatory response modulation. Serum levels of TNF, IFN-γ, TGF-β1, IL-6, IL-8, IL-10, and MIF were measured in 79 pregnant women (18–40 years old) during the third trimester of an uncomplicated pregnancy. Participants were divided into four groups: Group I—depressive disorder and T. gondii seropositive (n = 19); Group II—no depressive disorder and T. gondii seropositive (n = 20); Group III—depressive disorder and T. gondii seronegative (n = 20); and Group IV—no depressive disorder and T. gondii seronegative (n = 20). Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) during routine prenatal visits, and blood samples were collected during standard prenatal examinations. Significant differences in cytokine levels were observed among the study groups. Notably, the group with both depressive disorder and chronic T. gondii infection exhibited a distinct cytokine profile characterized by significantly elevated TNF, IL-6, and IL-10 levels and significantly reduced IL-8 and MIF levels compared to the other groups. These findings suggest that pregnant women with depressive disorder and chronic T. gondii infection exhibit an altered balance of pro- and anti-inflammatory cytokines. This is the first study to investigate the association between serum cytokine levels, depressive disorder, and chronic T. gondii infection in pregnant women. Further research is needed to evaluate the potential of these immunobiomarkers as diagnostic tools or for monitoring therapeutic and prognostic strategies in this context. Full article

Background/Objectives: Acridine, an aromatic heterocyclic compound, serves as a basis for the synthesis of potent bioactive derivatives, displaying a broad spectrum of biological activity, such as antibacterial, antitumor, and antiparasitic activity. With the ability to undergo various types of electrophilic substitutions, introducing different side chains could lead to compounds being active towards various and potentially multiple biotargets. Toxoplasma gondii, a ubiquitous protozoan parasite with worldwide distribution, poses a major health threat, particularly in immunocompromised patients and fetuses. Current treatment options for toxoplasmosis are scarce, with notable limitations, especially regarding side myelotoxicity and inactivity towards T. gondii cysts, causing a need for novel drug candidates. The aim of this study was to evaluate selected N-(9-acrydinil) amino acid derivatives as potential anti-T. gondii agents. Methods: Synthesis of new derivatives was performed using a two-step method, with the initial mixing of 9-chloroacridine with methanol and sodium alkoxide solution and subsequent adding of appropriate amino acids. Cytotoxicity of the tested compounds was evaluated on the Vero cell line using a MTT assay, while their anti-T. gondii activity was investigated using T. gondii RH strain tachyzoites. Results: CC₅₀ values of the derivatives ranged from 41.72 to 154.10 µM. Anti-T. gondii activity, displayed as a reduction in the number of viable tachyzoites compared to the untreated control, ranged from 0 to 33.3%. One of the derivatives displayed activity comparable to the standard treatment option while retaining acceptable cytotoxicity. Esterification, presence of aromatic substituents and the length of the amino acid side chain were identified as key factors that affect both toxicity and activity of these derivatives. Conclusions: Promising results obtained throughout this study provide guidelines for further structural modifications of N-(9-acrydinil) amino acid derivatives in order to synthesize drug candidates competitive to standard treatment options for toxoplasmosis. Full article

Pleopeltis crassinervata has demonstrated antimicrobial effects, including anti-Toxoplasma activity, which has been attributed to the presence of compounds such as terpenes and fatty acid methyl esters. In this study, the effects of P. crassinervata hexane subfraction one (Hsf1) on the Toxoplasma gondii tachyzoite ultrastructure were evaluated using TEM and SEM, and lytic cycle processes such as adhesion, invasion, and proliferation were evaluated using phase-contrast microscopy. Additionally, the antioxidant capacity of the subfraction and its main compounds (phytol and hexadecenoic acid methyl ester) were determined as well as their effects on parasite viability. Hsf1 exhibited a dose-dependent inhibitory effect on the lytic process at a concentration of 47.2 µg/mL. Among the eighteen compounds identified in this subfraction, six were evaluated, of which two (phytol and hexadecanoic acid methyl ester) significantly reduced the viability of T. gondii to 0.11% and 16.6%, respectively, at a concentration of 100 µg/mL. Additionally, Hsf1 demonstrated an antioxidant capacity of 30% as assessed using the ORAC method. The two active compounds also exhibited antioxidant properties, with antioxidant capacities of 13.33% and 33% for hexadecanoic acid methyl ester and phytol, respectively, at concentrations up to 15.4 mg/mL. Hsf1 showed membrane damage and conoid extrusion in T. gondii tachyzoites, suggesting direct interference with the lytic cycle of the parasite. These findings underscore the therapeutic potential of Hsf1 as a promising tool for controlling infections caused by T. gondii, thereby providing an alternative in the search for new antiparasitic agents. However, further research is required to determine the in vivo pharmacological effects and properties of these compounds with potential anti-Toxoplasma activity. Full article

Toxoplasmosis is a significant zoonotic parasitic disease. Currently, there is no effective vaccine available to prevent human infection, and treatment primarily relies on chemotherapy. However, the lack of specific therapeutic agents and the limitations of existing drugs highlight the urgent need for novel, safe, and effective anti-Toxoplasma gondii (T. gondii) medications. In this study, we evaluated the toxicity of ICA (N-(pyridin-2-yl)-4-(pyridine-2-yl)thiazol-2-amine) to host cells and assessed its inhibitory and anti-proliferative effects on T. gondii tachyzoites. We further investigated the impact of ICA on the ultrastructure of T. gondii using transmission electron microscopy (TEM). Additionally, we measured alterations in mitochondrial membrane potential, superoxide levels, and ATP levels in T. gondii to assess the effect of ICA on mitochondrial function. Our findings demonstrated that ICA exhibits a safe and effective inhibitory effect on T. gondii, with a selectivity index (SI) of 258.25. Notably, ICA demonstrated a more potent anti-proliferative effect than pyrimethamine (PYR). Ultrastructural observations revealed that ICA induces mitochondrial swelling and membrane rupture in T. gondii. Further investigations confirmed that ICA leads to mitochondrial dysfunction in T. gondii. In conclusion, our results suggest that ICA possesses the potential to serve as a lead compound for the development of novel anti-T. gondii therapies. Full article

Signal-dependent transport into and out of the nucleus mediated by members of the importin (IMP) superfamily is crucial for eukaryotic function, with inhibitors targeting IMPα being of key interest as anti-infectious agents, including against the apicomplexan Plasmodium species and Toxoplasma gondii, causative agents of malaria and toxoplasmosis, respectively. We recently showed that the FDA-approved macrocyclic lactone ivermectin, as well as several other different small molecule inhibitors, can specifically bind to and inhibit P. falciparum and T. gondii IMPα functions, as well as limit parasite growth. Here we focus on the FDA-approved antiparasitic moxidectin, a structural analogue of ivermectin, for its IMPα-targeting and anti-apicomplexan properties for the first time. We use circular dichroism and intrinsic tryptophan fluorescence measurements to show that moxidectin can bind directly to apicomplexan IMPαs, thereby inhibiting their key binding functions at low μM concentrations, as well as possessing anti-parasitic activity against P. falciparum in culture. The results imply a class effect in terms of IMPα’s ability to be targeted by macrocyclic lactone compounds. Importantly, in the face of rising global emergence of resistance to approved anti-parasitic agents, the findings highlight the potential of moxidectin and possibly other macrocyclic lactone compounds as antimalarial agents. Full article

Toxoplasma gondii is a protozoan, and the etiologic agent of toxoplasmosis, a disease that causes high mortality in immunocompromised individuals and newborns. Despite the medical importance of toxoplasmosis, few drugs, which are associated with side effects and parasite resistance, are available for its treatment. Here, we show a screening of molecules present in COVID-Box to discover new hits with anti-T. gondii activity. COVID-Box contains 160 molecules with known or predicted activity against SARS-CoV-2. Our analysis selected 23 COVID-Box molecules that can inhibit the tachyzoite forms of the RH strain of T. gondii in vitro by more than 70% at 1 µM after seven days of treatment. The inhibitory curves showed that most of these molecules inhibited the proliferation of tachyzoites with IC₅₀ values below 0.80 µM; Cycloheximide and (-)-anisomycin were the most active drugs, with IC₅₀ values of 0.02 μM. Cell viability assays showed that the compounds are not toxic at active concentrations, and most are highly selective for parasites. Overall, all 23 compounds were selective, and for two of them (apilimod and midostaurin), this is the first report of activity against T. gondii. To better understand the effect of the drugs, we analyzed the effect of nine of them on the ultrastructure of T. gondii using transmission electron microscopy. After treatment with the selected drugs, the main changes observed in parasite morphology were the arrestment of cell division and organelle alterations. Full article

Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis. It may produce severe damage in immunocompromised individuals, as well as congenital infection and intrauterine growth restriction (IUGR). Previous reports have associated interleukin IL-33 with miscarriage, fetal damage, and premature delivery due to infections with various microorganisms. However, IL-33 has not been associated with congenital toxoplasmosis. The sST2 receptor has been reported in patients who have had recurrent miscarriages. On the other hand, IL-1β was not found in acute Toxoplasma infection. Our aim was to analyze the associations between the serum levels of IL-33 and IL-1β in IUGR and toxoplasmosis during pregnancy. Eighty-four serum samples from pregnant women who had undergone 26 weeks of gestation were grouped as follows: with anti-Toxoplasma antibodies, without anti-Toxoplasma antibodies, IUGR, and the control group. IgG and IgM anti-T. gondii antibodies, as well as IL-33, ST2, and IL-1β, were determined using an ELISA assay. Statistical analyses were performed using the Pearson and Chi-square correlation coefficients, as well as the risk factors and Odds Ratios (ORs), with a confidence interval of 95% (CI 95). The results showed that 15/84 (17.8%) of cases were positive for IgG anti-Toxoplasma antibodies and 2/84 (2.38%) of cases were positive for IgM. A statistically significant difference was found between IUGR and IL-33 (p < 0.001), as well as between ST2 and IUGR (p < 0.001). In conclusion, IUGR was significantly associated with IL-33 and ST2 positivity based on the overall IUGR grade. No significant association was found between IUGR and the presence of anti-Toxoplasma antibodies. There was no association between IL-1β and IUGR. More research is needed to strengthen the utility of IL-33 and ST2 as biomarkers of IUGR. Full article

Toxoplasmosis is a globally prevalent zoonotic disease with significant clinical implications, including neurotoxoplasmosis, a leading cause of cerebral lesions in AIDS patients. The current pharmacological treatments for toxoplasmosis face clinical limitations, necessitating the urgent development of new therapeutics. Natural sources have yielded diverse bioactive compounds, serving as the foundation for clinically used derivatives. The exploration of marine bacteria-derived natural products has led to marinoquinolines, which feature a pyrroloquinoline core and demonstrate in vitro and in vivo anti-Plasmodium activity. This study investigates the in vitro anti-Toxoplasma gondii potential of six marinoquinoline derivatives. Additionally, it conducts absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, and evaluates the in vivo efficacy of one selected compound. The compounds displayed half-maximal effective concentration (EC₅₀) values between 1.31 and 3.78 µM and half-maximal cytotoxic concentration (CC₅₀) values ranging from 4.16 to 30.51 µM, resulting in selectivity indices (SI) from 3.18 to 20.85. MQ-1 exhibiting the highest in vitro SI, significantly reduced tachyzoite numbers in the peritoneum of RH-infected Swiss mice when it was orally administered at 12.5 mg/kg/day for eight consecutive days. Also, MQ-1 significantly reduced the cerebral parasite burden in chronically ME49 infected C57BL/6 mice when it was orally administered at 25 mg/kg/day for 10 consecutive days. These findings underscore the promising anti-T. gondii activity of marinoquinolines and their potential as novel therapeutic agents against this disease. Full article

Cytomegalovirus (CMV), in addition to other agents, is part of the TORCH complex (Toxoplasma gondii, Rubella virus, Cytomegalovirus, Herpes simplex viruses, and other agents). CMV infection is the most frequent cause of congenital malformations. This study aimed to establish the variation of prevalence of anti-CMV antibodies in pregnant women from the South-West region of Romania, according to demographic factors, such as age and area of residence, in two separate time periods (2013–2016 and 2019–2022). We collected from the hospital records the age, place of residence, and anti-CMV antibody test results using immune electrochemiluminescence and chemiluminescence. This study found that the seroprevalence of anti-CMV IgM antibodies increased slightly from 2013–2016 to 2019–2022, from 1.92% to 2.26%, and for IgG antibodies from 93.68% to 94.96%. In both groups was observed a descending trend of anti-CMV IgM seroprevalence with an increase in age, showing a decrease in seroprevalence from 3.57% to 1.09% in pregnant women from rural areas in the 31–35 years age group, while in urban areas, we observed a decrease in seroprevalence from 11.11% to 3.06% in the <20 years age group. The IgG seroprevalence showed an increase both in rural areas (from 93.97% to 95.52%) and urban areas (from 93.52% to 94.27%). In both groups, seroprevalence was higher in rural areas compared to urban regions. These results show a high rate of immunization against CMV in pregnant women in South-West Romania, which led to a low risk of acquiring the primary infection during pregnancy. However, the increase in the rate of primary CMV infections in pregnancy suggests the need for prioritizing screening programs and improving the existing protocols to enhance maternal and child healthcare. Full article

Maternal–fetal infectious pathology—notably the TORCH panel (Toxoplasma gondii, rubella, Cytomegalovirus, and herpes simplex viruses)—critically impacts maternal and neonatal health. This review collates data on the seroprevalence of IgG and IgM antibodies against TORCH agents in Romanian women, aiming to discern regional and population differences and identify risk factors. Twenty studies were included in the review, revealing variable seroprevalence rates across the country. Regions such as Moldavia and Banat showed higher anti-T. gondii IgG seroprevalence rates than Bihor, with notable declines in Banat. Rural, older, and multiparous women showed elevated T. gondii IgG rates. Anti-rubella vaccine introduction significantly reduced the prevalence of anti-rubella IgG antibodies, but recent vaccination coverage decreases raise concerns. CMV and HSV seroprevalence varied geographically, with rural areas generally showing higher CMV rates and HSV influenced by factors like education level and number of sexual partners. Concurrent seroprevalence of multiple TORCH components in some cases underscores potential common risk factors. This study highlights the importance of continuous monitoring and preventive measures such as vaccinations and awareness campaigns to mitigate the health impact on the pregnant population. Full article

Toxoplasma gondii and Neospora caninum are obligate intracellular intestinal coccidia distributed worldwide, and are causative agents of toxoplasmosis and neosporosis, respectively. The aim of this study was to evaluate the prevalence of anti-T. gondii and anti-N. caninum antibodies and the factors associated with infections in beef cattle intended for human consumption in an Amazonian area of North Brazil. We collected blood samples of 387 cattle from 50 herds located in different municipalities of the State of Rondônia. An epidemiological questionnaire was distributed to farmers, with regard to nutritional, sanitary and reproductive herd management. The samples were identified, refrigerated and sent for serological analyses via IFAT (Immunofluorescent Antibody Test). Among the 387 analyzed animals, 91 (23.5%; CI 95%: 18.8–27.2) were positive for anti-T. gondii antibodies, with titers varying from 1:64 (75.8%) to 1:512 (2.2%). For anti-N. caninum antibodies, only four animals (1%; CI 95%: 0–2.7) were positive, with titers ranging from 1:400 (50%) to 1:1600 (25%). We observed a significant rate of anti-T. gondii antibodies in the variables “pure breed” and “contact with free-range chickens” (p < 0.2). There were no risk factors associated with the presence of anti-T. gondii or anti-N. caninum antibodies. In conclusion, there was a high prevalence of anti-T. gondii antibodies in beef cattle intended for human consumption in the State of Rondônia, Brazil, and a low prevalence of anti-N. caninum antibodies. Longitudinal studies can better elucidate the cause of these prevalence levels and how they could be better prevented and controlled. Full article

SARS-CoV-2 is the causal agent of COVID-19; the first report of SARS-CoV-2 infection was in December 2019 in Wuhan, China. This virus has since caused the largest pandemic in history, and the number of deaths and infections has been significant. Nevertheless, the development of vaccines has helped to reduce both deaths and infections. Comorbidities such as diabetes, hypertension, heart and lung diseases, and obesity have been identified as additional risk factors for infection and the progression of COVID-19. Additionally, latent toxoplasmosis has been reported to be a risk factor for acquiring COVID-19 in some studies, but other studies have suggested a negative association between these two infections. Furthermore, in patients after vaccination or with COVID-19 and coinfection, an increase in the lethality and mortality of toxoplasmosis has been observed. Therefore, the objective of the current study is to determine the association of toxoplasmosis with COVID-19 in patients diagnosed with COVID-19. Serum samples from 384 patients previously diagnosed with COVID-19 using IgG antibodies against the S1/S2 antigens of SARS-CoV-2 were collected. Subsequently, anti-Toxoplasma IgG and IgM antibodies were analyzed with ELISA. Statistical analysis was performed using SPSS Version 20.0 frequencies, percentages, 2 × 2 tables, and the Pearson correlation coefficient. IgG and IgM anti-Toxoplasma antibodies were positive in 105/384 (27.34%) and (26/191) 13.6% of patients, respectively. The positivity for both infections was higher in patients aged >40 years old. Subjects who were overweight or obese were mainly positive for both IgG antibodies against S1/S2 SARS-CoV-2 and Toxoplasma antibodies. In conclusion, the coinfection rate was 21.7%. The prevalence of S1/S2 SARS-CoV-2 was 308/384 (80.2%), and the percentage of Toxoplasma antibodies was 27.34%. Full article

Currently, toxoplasmosis affects nearly one-third of the world’s population, but the available treatments have several limitations. This factor underscores the search for better therapy for toxoplasmosis. Therefore, in the current investigation, we investigated the potential of emodin as a new anti-Toxoplasma gondii while exploring its anti-parasitic mechanism of action. We explored the mechanisms of action of emodin in the presence and absence of an in vitro model of experimental toxoplasmosis. Emodin showed strong anti-T. gondii action with an EC₅₀ value of 0.03 µg/mL; at this same effective anti-parasite concentration, emodin showed no appreciable host cytotoxicity. Likewise, emodin showed a promising anti-T. gondii specificity with a selectivity index (SI) of 276. Pyrimethamine, a standard drug for toxoplasmosis, had an SI of 2.3. The results collectively imply that parasite damage was selective rather than as a result of a broad cytotoxic effect. Furthermore, our data confirm that emodin-induced parasite growth suppression stems from parasite targets and not host targets, and indicate that the anti-parasite action of emodin precludes oxidative stress and ROS production. Emodin likely mediates parasite growth suppression through means other than oxidative stress, ROS production, or mitochondrial toxicity. Collectively, our findings support the potential of emodin as a promising and novel anti-parasitic agent that warrants further investigation. Full article

The uncontrolled increasing clinical resistance to the current anti-parasitic drugs towards important protozoan parasites (Plasmodium, Leishmania, Trypanosoma and Toxoplasma) has stimulated the search for novel and safe therapeutic agents at affordable prices for countries in which these parasites are endemic. For the past few decades, the criticality of the cationic lipid stearylamine (SA) in liposomes has been explored in these human parasites. Previously, SA was incorporated in the liposomal formulation to impart a net positive charge for enhanced cellular uptake. However, the discovery of SA in liposomes alone elicits a strong anti-parasitic activity with immunomodulatory potential. Additionally, the SA liposome possesses a significant inhibitory potential on multiple life stages of the parasite cycle and delivers an equal effect on both drug-sensitive and resistant parasites. Moreover, the delivery of standard anti-parasitic drugs using SA liposome vesicles has enhanced the efficacy of drugs due to the synergistic impacts without causing any apparent toxicity on the host cells. In addition, the delivery of antigens as vaccine candidates using SA liposomes elicits a pronounced immune response in clearing the infection compared to other cationic lipids and SA-free liposomes. Nonetheless, SA liposome mediates its anti-parasitic activity by targeting the negatively charged phosphatidylserine-exposed infected host cell surface or by interaction with negatively charged sialic acid of free-living parasites. Overall, SA liposome confers its protection by acting as a chemotherapeutic agent with immunomodulatory activity. Therefore, a broadly acting anti-parasitic agent (SA liposome) is promising in tackling the deadly parasitic infections in endemic regions and warrants further clinical investigations. Full article