Dataset Information

Treatment of Murine Toxoplasmosis with Oral and Parenteral Artemether and Following by Detection of B1 Gene by Quantitative Real-Time PCR (qPCR) for Evaluating Parasite Density.

ABSTRACT:

Background

Toxoplasma gondii is an obligate intracellular parasite that can infect humans and animals. As the choice drug have shown side effects, development a new drug with low toxicity will be necessary.

Methods

BALB/c mice were infected with tachyzoiets of T. gondii. After treatment by oral and parenteral artemether (250 μg/mice) and sulfadiazine (50 μg/mice), we evaluated the rates of survival in treated and control mice. The fold change of B1 gene (target gene) expression in liver and brain of mice treated with parenteral artemether (i.p.), oral artemether (via gavage) and sulfadiazine, were detected by using the Real-Time quantitative PCR.

Results

Both treatment with sulfadiazine and artemether showed significant prolongation in time to death of the infected mice compared to the control group. Median survival days for parenteral artemether, oral artemether, sulfadiazine and control group were 8, 11, 12 and 6 d respectively. Expression of B1 gene in liver and brain of mice after treatment with artemether and sulfadiazine were reduced in comparison to housekeeping gene (β-tubulin gene). The fold change (comparing to control group) for parenteral artemether, oral artemether, sulfadiazine is 0.034, 0.027 and 0.111 for liver and 0.220, 0.425 and 0.366 for brain respectively.

Conclusion

Artemether is effective to control the tachyzoites of T. godii in vivo conditions and oral treatment is more effective than parenteral treatment. Due to its low cytotoxicity and its high effective action against the tachyzoietes of T. godii in susceptible animals.

SUBMITTER: Mikaeiloo H

PROVIDER: S-EPMC9375721 | biostudies-literature | 2022 Jan-Mar

REPOSITORIES: biostudies-literature

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Publications

Treatment of Murine Toxoplasmosis with Oral and Parenteral Artemether and Following by Detection of <i>B1</i> Gene by Quantitative Real-Time PCR (qPCR) for Evaluating Parasite Density.

Mikaeiloo Hajar H Ghaffarifar Fatemeh F Dalimi Abdolhossein A Zuhair Hassan Mohammad M Sharifi Zohreh Z

Iranian journal of parasitology 20220101 1

<h4>Background</h4><i>Toxoplasma gondii</i> is an obligate intracellular parasite that can infect humans and animals. As the choice drug have shown side effects, development a new drug with low toxicity will be necessary.<h4>Methods</h4>BALB/c mice were infected with tachyzoiets of <i>T. gondii</i>. After treatment by oral and parenteral artemether (250 μg/mice) and sulfadiazine (50 μg/mice), we evaluated the rates of survival in treated and control mice. The fold change of B1 gene (target gene) ...[more]

PMID: 36046558

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Project description:Toxoplasma gondii, a protozoan parasite, causes toxoplasmosis, a widespread zoonotic and food-borne infection that poses significant risks, particularly in opportunistic and congenital cases. This obligate intracellular parasite is highly prevalent worldwide, largely due to its versatile life cycle, involving multiple hosts and transmission routes, and its ability to establish chronic infections. The presence of this neurotropic parasite in the brain poses a reactivation risk in immunocompromised individuals and might be associated with a higher likelihood of developing mental disorders. However, the role of the dormant bradyzoite stage in the pathophysiology of the disease is underexplored, mainly due to the lack of non-invasive detection methods and serologic tests targeting bradyzoite- or cyst-specific antigens. In this study, we performed an unbiased screening of the bradyzoite proteome and identified the Bradyzoite Serological Marker (BSM) as an additional serological biomarker, alongside the cyst-associated BCLA, to detect chronic stages in vivo. BSM and BCLA show high sensitivity and specificity in identifying cyst-bearing mice. However, in humans, these markers exhibit only moderate concordance, with a 30% positivity rate among individuals with prior immunity, suggesting variability in immune responses and complexities in diagnosing chronic toxoplasmosis. Importantly, bradyzoite serology helps differentiate recent from past infections by the teratogenic parasite Toxoplasma gondii, with BCLA improving the accuracy of pergestational infection diagnosis. Exploring the regulatory mechanisms controlling the expression of these markers revealed that the chromatin modifiers MORC and HDAC3 exert epistatic control over BFD1, a key regulator of bradyzoite development. While BFD1 governs a specific subset of bradyzoite markers, including BCLA, a sub-transcriptome comprising BSM relies on MORC/HDAC3 independently of BFD1. This complex gene regulation highlights the challenge in understanding Toxoplasma persistence, while offering new opportunities for improved serological diagnosis of congenital and chronic toxoplasmosis, particularly in individuals with mental health conditions or a risk of toxoplasmic reactivation.