In Vitro and in Vivo Effects of Nitrofurantoin on Experimental Toxoplasmosis

Abstract

Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.

Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites

“…A decrease in rectal temperatures has also been described in experiments testing toltrazuril against neosporosis in calves ( Kritzner et al, 2002 ) and monensin ( Buxton et al, 1988 ) or decoquinate ( Buxton et al, 1996 ) against toxoplasmosis in pregnant ewes. Additionally, since AST typically increases after T. gondii infection, indicating liver injury ( Yeo et al, 2016 ), the increased AST in G5 and not in G1 and G3 at the final time point might indicate that treated pregnant ewes exerted better control of N. caninum infection.…”

Synthesis and Anti-toxoplasma Activity in Vitro of Chrysin Derivatives

“…化合物 2 以二氯甲烷为溶剂, 与各种苄胺类、苯 胺类、脂肪胺类以及杂环类化合物于-10 ℃条件下反 应 [17] , 得到目标化合物 A1～A5、B1～B7、C1～C2、 D1～D4, 总收率 53.4%～72.4%. [15] .…”

“…本实验设计并合成了 4 个系列(A1～A5, B1～B7, C1～C2, D1～D4)共 18 个未见报道的白杨素衍生物. 在 体外实验中, 不同受试化合物的抗弓形虫活性我们用选 择性指数(SI)来表达 [15] . 由以上实验数据可知先导物白 杨素的 SI 值(0.82)略小于阳性对照药磺胺嘧啶的 SI 值 (0.91), 这表明白杨素具有一定的抗弓形虫活性, 但其 疗效略低于磺胺嘧啶.…”

Lectins from Synadenium carinatum (ScLL) and Artocarpus heterophyllus (ArtinM) Are Able to Induce Beneficial Immunomodulatory Effects in a Murine Model for Treatment of Toxoplasma gondii Infection

“…The strategies for toxoplasmosis treatment still show serious limitations, particularly due to the high degree of toxicity that has been associated with the current chemotherapy (Yeo et al, 2016). Also, the possibility to occur parasite drug resistance is an additional drawback to treat this disease based only on chemotherapy (Hui et al, 2015).…”