Graduate Program in Health Sciences, Center for Biological and Health Sciences, Federal University of Maranhão, São Luís, MA, Brazil.
Graduate Program in Health Sciences, Center for Biological and Health Sciences, Federal University of Maranhão, São Luís, MA, Brazil; Department of Education, Federal Institute of Education, Science and Technology of Maranhão, Zé Doca, MA, Brazil.
Mol Biochem Parasitol. 2022 Nov;252:111531. doi: 10.1016/j.molbiopara.2022.111531. Epub 2022 Nov 11.
Praziquantel (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis, although its mechanisms of action are not completely understood. PZQ acts largely on adult worms. This narrative literature review describes what is known about the mechanisms of action of PZQ against schistosomes from in vitro and in vivo studies and highlights the molecular targets in parasites and immune responses induced in definitive hosts by this drug. Moreover, new therapeutic uses of PZQ are discussed. Studies have demonstrated that in addition to impacting voltage-operated Ca2 + channels, PZQ may interact with other schistosome molecules, such as myosin regulatory light chain, glutathione S-transferase, and transient receptor potential channels. Following PZQ administration, increased T regulatory type 1 (Tr1) cell differentiation and decreased inflammation were observed, indicating that PZQ promotes immunoregulatory pathways. Although PZQ is widely used in mass drug administration schemes, the existence of resistant parasites has not been proven; however, it is a concern that should be constantly investigated in human populations. In addition, we discuss studies that evaluate health applications of PZQ (other than helminth infection), such as its effect in cancer therapy and its adjuvant action in vaccines against viruses.
吡喹酮(PZQ)是治疗所有形式血吸虫病的首选药物,尽管其作用机制尚不完全清楚。PZQ 主要作用于成虫。本综述描述了从体外和体内研究中已知的 PZQ 对血吸虫作用机制,并强调了该药物在寄生虫中的分子靶标和在终宿主中诱导的免疫反应。此外,还讨论了 PZQ 的新治疗用途。研究表明,除了影响电压门控 Ca2+通道外,PZQ 还可能与其他血吸虫分子相互作用,如肌球蛋白调节轻链、谷胱甘肽 S-转移酶和瞬时受体电位通道。在给予 PZQ 后,观察到调节性 T 细胞 1 型(Tr1)分化增加和炎症减少,表明 PZQ 促进免疫调节途径。尽管 PZQ 广泛用于大规模药物治疗方案中,但尚未证明存在耐药寄生虫;然而,应该在人类群体中不断调查这一令人关注的问题。此外,我们还讨论了评估 PZQ 的健康应用(除了寄生虫感染)的研究,例如其在癌症治疗中的作用及其在针对病毒的疫苗中的佐剂作用。