Effects of Auranofin on the proliferation of Toxoplasma gondii by promoting autophagy

Abstract:

Objective：To study the effect of Auranofin on Toxoplasma gondii tachyzoites and the autophagy in mice infected with Tox－oplasma gondii. Methods：The changes of Toxoplasma gondii ultrastructure were observed before and after treatment by transmission electron microscopy. The changes of autophagy protein LC3 in brain tissue with Toxoplasma gondii were detected by immunofluores－cence，immunohistochemistry and immunoblotting. The changes of Toxoplasma gondii tachyzoites in the brain of mice were ob－served by HE staining. Results：The transmission electron microscopy showed that in 10 ?滋g/mL group（group B），the internal struc－ture of Toxoplasma tachyzoite was destroyed，the cell membrane of the worm was ruptured，and the cytoplasm structure changed，while in 20 ?滋g/mL group（group C），the insect body content overflowed，the mitochondria and rough endoplasmic reticulum disappeared，karyopyknosis was shown，nuclear membrane was ruptured，many vacuoles presented in the cytoplasm，and in more serious situation，the insect body collapsed and presented a homogenous change. The results of immunofluorescence showed that the expression of LC3 protein in the experimental group（77.49±15.68） was significantly higher than that in the control group（53.81±15.24）（P=0.001）. The results of immunohistochemistry showed that the expression of LC3 protein was significantly increased after treatment（1 208.55±580.07 vs. 544.54±225.04）（P=0.000）. The results of immunoblotting assay showed that after treatment，the expression of LC3 protein was significantly higher（41 738.52±0.00） than that in the control group（25 383.88±607.34）（P=0.000）. After treatment，the proliferation of Toxoplasma gondii Tachyzoites in the brain of mice was significantly less（218.80±21.17） than that in the control group（495.40±31.91）（P=0.000）. Conclusions：Auranofin can destroy Toxo－plasma gondii tachyzoites in vitro，and meanwhile promote the autophagy of mice infected with Toxoplasma gondii to inhibit the proliferation of Toxoplasma gondii.