Tropical Pathology and Public Health Institute, Federal University of Goias, Goiás, Rua 235, S/n, Setor Leste Universitário, CEP 74605-050, Brazil.
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiás, Rua 235, S/n, Setor Leste Universitário, CEP 74605-050, Brazil.
Exp Parasitol. 2020 Jan;208:107792. doi: 10.1016/j.exppara.2019.107792. Epub 2019 Nov 7.
Nitazoxanide (NTZ) is a broad-spectrum drug used in intestinal infections, but still poorly explored in the treatment of parasitic tissular infections. This study aimed to evaluate the in vitro responses of the energetic metabolism of T. crassiceps cysticerci induced by NTZ. The organic acids of the tricarboxylic acid cycle, products derived from fatty acids oxidation and protein catabolism were analyzed. These acids were quantified after 24 h of in vitro exposure to different NTZ concentrations. A positive control group was performed with albendazole sulfoxide (ABZSO). The significant alterations in citrate, fumarate and malate concentrations showed the NTZ influence in the tricarboxylic acid (TCA) cycle. The non-detection of acetate confirmed that the main mode of action of NTZ is effective against T. crassiceps cysticerci. The statistical differences in fumarate, urea and beta-hydroxybutyrate concentrations showed the NTZ effect on protein catabolism and fatty acid oxidation. Therefore, the main energetic pathways such as the TCA cycle, protein catabolism and fatty acids oxidation were altered after in vitro NTZ exposure. In conclusion, NTZ induced a significant metabolic stress in the parasite indicating that it may be used as an alternative therapeutic choice for cysticercosis treatment. The use of metabolic approaches to establish comparisons between anti parasitic drugs mode of actions is proposed.
硝唑尼特(NTZ)是一种广谱药物,用于治疗肠道感染,但在寄生虫组织感染的治疗方面研究甚少。本研究旨在评估硝唑尼特(NTZ)诱导的曼氏血吸虫囊蚴能量代谢的体外反应。分析三羧酸循环中的有机酸、脂肪酸氧化和蛋白质分解代谢的产物。在体外暴露于不同浓度的 NTZ 24 小时后,对这些酸进行定量。用阿苯达唑亚砜(ABZSO)进行阳性对照。柠檬酸、富马酸和苹果酸浓度的显著变化表明 NTZ 对三羧酸(TCA)循环有影响。未检测到醋酸盐证实 NTZ 的主要作用模式对曼氏血吸虫囊蚴有效。富马酸、尿素和β-羟基丁酸浓度的统计学差异表明 NTZ 对蛋白质分解代谢和脂肪酸氧化有影响。因此,TCA 循环、蛋白质分解代谢和脂肪酸氧化等主要能量途径在体外 NTZ 暴露后发生了改变。总之,硝唑尼特在寄生虫中诱导了显著的代谢应激,表明它可能被用作囊尾蚴病治疗的替代治疗选择。建议使用代谢方法来建立抗寄生虫药物作用模式之间的比较。