Montazeri Mahbobeh, Emami Saeed, Asgarian-Omran Hossein, Azizi Soheil, Sharif Mehdi, Sarvi Shahabeddin, Rezaei Fatemeh, Sadeghi Mitra, Gohardehi Shaban, Daryani Ahmad
Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran; Department of Parasitology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Exp Parasitol. 2019 May;200:7-12. doi: 10.1016/j.exppara.2019.03.009. Epub 2019 Mar 20.
As current toxoplasmosis chemotherapies have many side effects along with toxicity on patients, we examined the anti-Toxoplasma effect of a biologically important natural antibiotic, kojic acid, in vitro and in vivo. Vero cells were incubated with different concentrations of kojic acid or pyrimethamine (positive control), and the cellular viability was determined. Next, Vero cells were infected with T. gondii (RH strain) and treated with drugs. Then, we calculated the infection index, T. gondii intracellular proliferation and the number and measure of plaque. Moreover, the effect of kojic acid on survival times, serum levels of IFN-γ and TNF-α and histopathological changes in the liver and spleen of Balb/c mice infected with T. gondii were determined. Kojic acid reduced the infection index, intracellular proliferation, the number and measure of plaque in vitro when compared to untreated infected cells. Kojic acid (100 mg/kg/day) also showed a better survival rate than infected untreated control mice (P < 0.05). IFN-γ and TNF-α secretions were significantly increased by kojic acid treatment in comparison to untreated groups (P < 0.05). In addition, its inhibitory effects on inflammatory alterations, apoptosis, and necrosis have been shown in sections of liver and spleen. We conclude that kojic acid exhibit potent anti-Toxoplasma activity with direct and indirect effects on the parasite, although further studies are needed before consideration of clinical trials.
由于目前的弓形虫病化疗方法对患者有许多副作用以及毒性，我们在体外和体内研究了一种具有重要生物学意义的天然抗生素曲酸对弓形虫的作用。将Vero细胞与不同浓度的曲酸或乙胺嘧啶（阳性对照）孵育，并测定细胞活力。接下来，用弓形虫（RH株）感染Vero细胞并用药物处理。然后，我们计算感染指数、弓形虫细胞内增殖以及噬斑的数量和大小。此外，还测定了曲酸对感染弓形虫的Balb/c小鼠的存活时间、血清中IFN-γ和TNF-α水平以及肝脏和脾脏组织病理学变化的影响。与未处理的感染细胞相比，曲酸在体外降低了感染指数、细胞内增殖、噬斑的数量和大小。曲酸（100mg/kg/天）也显示出比未处理的感染对照小鼠更好的存活率（P<0.05）。与未处理组相比，曲酸处理显著增加了IFN-γ和TNF-α的分泌（P<0.05）。此外，在肝脏和脾脏切片中显示了其对炎症改变、凋亡和坏死的抑制作用。我们得出结论，曲酸对弓形虫具有强大的抗弓形虫活性，对寄生虫有直接和间接作用，尽管在考虑进行临床试验之前还需要进一步研究。
