| Toxoplasma gondii,an obligate intracellular protozoan parasite,is the causative agent of toxoplasmosis that has the ability to infect any endotherm of vertebrata.Approximately one third of the world~'s population has been infected with T.gondii.Toxoplasmosis is a widespread zoonosis which can cause great harms to humans and animal.Sulfadiazine Sodium(SDZ)is one of the best drugs of the world to treat toxoplasmosis.While,numerous studies have found these toxicity problems in the process of using sulfadiazine,while SDZ is still the dominating drug to improve toxoplasmosis.SDZ can block the folate biosynthesis pathway by restraining dihydrofolate reductase(DHFR),thereby interfering the parasite replication in body and reaching the purpose of treatment.In addition,it is yet to know whether sulfadiazine treatment of toxoplasmosis also affect the changes of physiological and pathological in the host.Therefore,the objectives of this study were to explore the serum metabolic changes of the host during the treatment of toxoplasmosis with SDZ and to find out the mechanism of the drug treatment of toxoplasmosis on the body;Moreover,explore the disease form acute to chronic recovery of SDZ-treated mice infected with the GT1 strain of T.gondii.This study used Balb/C mice to establish model of infection and treatment.Toxoplasmosis was treated by SDZ to achieve an acute-to-chronic outcome in mice infected with T.gondii(GT1)and the Toxoplasma cysts were detected in the mouse brain during chronic phase.In the present study,liquid chromatography-mass spectrometry(LC-MS/MS)was used to analyze the serum metabolomics of different experimental mice.In the positive and negative ion modes,9894 and 6532 ion peaks were detected,respectively,by principal component analysis(PCA)and partial least square analysis(PLS-DA).The mice that had not been treated with drugs appeared systemic metabolic disorder at 6 days after the infection with T.gondii.While,the mice treated by SDZ had only a small metabolic difference at the same period.After treatment for 12 days and then off drenching SDZ,the mice showed typical symptoms of acute phase,and the host's metabolism also were significantly disturbed.And then off drenching SDZ 16 days,the mice overall state gradually stabilized and the host's metabolic fluctuations also became moderate.This study demonstrates that the host's metabolic changes are consistent with the host's symptoms during treatment.Lipid latent markers were identified by receiver operating characteristic(ROC)analysis in the Acute in comparison with Control.The metabolites of the mouse serum and its affected metabolic pathways during the course of treatment were analyzed and revealed that“lipids and lipid molecules”accounted for more than half of the total metabolites,and also discovered during the entire experiment through topological analysis,affected linoleic acid metabolism,?-linoleic acid metabolism,sphingolipid metabolism,and glycerophospholipid metabolism are the five metabolic pathways.It was found that the evasion mechanism of T.gondii in the host or SDZ may direct or indirect affect the phospholipase A2(PLA2)-mediated inflammatory mechanism.This study explored the disease recovery of SDZ-treated mice infected with the GT1strain of T.gondii,and the Toxoplasma cysts were detected in the mouse brain during chronic phase for the first time.Which may make possible for the establishment of a model of oral infection by infecting with GT1 cyst in mice and the study of post-infection pathophysiological immunology and may also provide an opportunity to analyze the transformation process of the GT1 parasite from the tachyzoite to the bradyzoite stage and gene expression for control this process.The present study also examined the serum metabolic changes of T.gondii infected mice in SDZ treatment.The results have important implications for better understanding of the therapeutic effects of SDZ and may also provide useful data support for discovery of new ways for the treatment of toxoplasmosis. |
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