Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentiev Ave., Novosibirsk 630090, Russia.
Shanghai Tenth People's Hospital, Institute for Infectious Diseases and Vaccine Development, Tongji University School of Medicine, 301 Middle Yanchang Road., Shanghai 200072, China.
Acta Trop. 2021 Aug;220:105954. doi: 10.1016/j.actatropica.2021.105954. Epub 2021 May 9.
Anthelmintic praziquantel (PZQ) is the drug of the choice for opisthorchiasis, schistosomiasis and other trematodiases therapy for several decades. Despite its good therapeutic performance and effective control of trematode infections, PZQ has some shortcomings; its inability to counteract disease sequelae necessitates novel therapeutic strategies. Testing of antioxidants that have proven themselves in clinical practice, in combination with this anthelmintic drug, offers new opportunities for developing alternatives to PZQ monotherapy. The effects of two antioxidants combined with PZQ on histological parameters of liver tissue were evaluated in a hamster model of opisthorchiasis felinea. Liver pathology including the parenchyma state, accumulation of neutral lipids and 4-Hydroxy-2-nonenal as a lipid peroxidation product, biochemical characteristics of hamster blood serum, and mRNA expression of inflammation- and fibrogenesis-associated genes were determined. PZQ and opisthorchiasis caused liver accumulation of lipids and glycogen. The combination of PZQ with resveratrol (RSV) or 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) significantly reduced hepatocyte changes (P = 0.009 and P = 0.009, respectively, Mann-Whitney U test) as compared with infected hamsters treated only with PZQ. RSV and SkQ1 significantly reduced cholangiocyte hyperplasia, bile duct proliferation, fibrosis, and lipid droplet and glycogen granule accumulation. The downregulation of 4-hydroxynonenal was also observed. The combinations of the anthelmintic drug with antioxidants RSV and SkQ1 ameliorate host oxidative stress and mitigate adverse effects of PZQ on hepatic parenchyma. The use of drug combinations may improve the action of standard anthelmintic agents, such as PZQ, which still remains the most effective agent against adult trematodes.
抗蠕虫药吡喹酮 (PZQ) 作为一种药物，在过去几十年中一直被用于治疗华支睾吸虫病、血吸虫病和其他吸虫病。尽管它具有良好的治疗效果和对吸虫感染的有效控制，但 PZQ 也存在一些缺点；它无法对抗疾病的后遗症，这就需要新的治疗策略。在临床实践中已经证明有效的抗氧化剂的测试，与这种驱虫药物结合使用，为开发替代 PZQ 单一疗法的新方法提供了新的机会。在猫后睾吸虫病的仓鼠模型中，评估了两种抗氧化剂与 PZQ 联合使用对肝组织组织学参数的影响。评估了包括肝实质状态、中性脂质积累和脂质过氧化产物 4-羟基-2-壬烯醛在内的肝病理学、仓鼠血清的生化特征以及与炎症和纤维化相关的基因的 mRNA 表达。PZQ 和后睾吸虫病导致肝内脂质和糖原积累。与仅用 PZQ 治疗的感染仓鼠相比，PZQ 与白藜芦醇 (RSV) 或 10-(6'-质体醌基) 癸基三苯基膦 (SkQ1) 的组合显著降低了肝细胞变化 (P=0.009 和 P=0.009，Mann-Whitney U 检验)。RSV 和 SkQ1 显著减少了胆管细胞增生、胆管增殖、纤维化以及脂滴和糖原颗粒的积累。还观察到 4-羟壬烯醛的下调。驱虫药与抗氧化剂 RSV 和 SkQ1 的组合可改善宿主氧化应激并减轻 PZQ 对肝实质的不良影响。药物组合的使用可能会改善标准驱虫药物（如 PZQ）的作用，PZQ 仍然是治疗成虫吸虫最有效的药物。
