Rodrigues Débora Caroline do Nascimento, Porto Jhonatas Cley Santos, Dos Santos Ingredy Lopes, Filho José Ivo Araújo Beserra, Ferreira Paulo Michel Pinheiro
Laboratory of Experimental Cancerology (LabCancer), Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piauí (UFPI), Universitaria Avenue, Teresina, Piauí, 64049-550, Brazil.
Inflammopharmacology. 2025 Feb;33(2):551-571. doi: 10.1007/s10787-024-01605-w. Epub 2024 Nov 26.
Acute, uncontrolled and/or long-lasting inflammation causes a breakdown in immunological tolerance, leading to chronicity and contributing to a series of significant local or systemic tissue changes. Anti-inflammatory efficacy, fewer adverse effects, improved selectivity, and curative action are imminent issues for patients suffering from chronic inflammation-related pathologies. Then, we performed a complete and critical review about anthelmintics, discussing the main classes and the available preclinical evidence on repurposing to treat inflammation-based conditions. Despite low bioavailability, many benzimidazoles (albendazole and mebendazole), salicylanilides (niclosamide), macrocyclic lactones (avermectins), pyrazinoisoquinolones (praziquantel), thiazolides (nitazoxanide), piperazine derivatives, and imidazothiazoles (levamisole) indicate that repositioning is a promising strategy. They may represent a lower cost and time-saving course to expand anti-inflammatory options. Although mechanisms of action are not fully elucidated and well-delineated, in general, anthelmintics disrupt mitogen-activated protein kinases, the synthesis of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-12, and IFN-γ), the migration and infiltration of leukocytes, and decrease COX-2 expression, which impacts negatively on the release of prostanoids and leukotrienes. Moreover, some of them reduce nuclear accumulation of NF-κB (niclosamide, albendazole, and ivermectin), levels of nitric oxide (nitazoxanide and albendazole), and mucus, cytokines, and bronchoconstriction in experimental inflammatory pulmonary diseases (ivermectin and niclosamide). Considering the linking between cytokines, bradykinin, histamine, and nociceptors with algesia, anthelmintics also stand out for treating inflammatory pain disorders (ivermectin, niclosamide, nitazoxanide, mebendazole, levamisole), including for cancer-related pain status. There are obstacles, including the low bioavailability and the first-pass metabolism.
急性、失控性和/或持续性炎症会导致免疫耐受的破坏，进而引发慢性炎症，并促使一系列显著的局部或全身组织变化。对于患有慢性炎症相关病症的患者而言，抗炎疗效、更少的不良反应、更高的选择性以及治疗作用是亟待解决的问题。随后，我们对驱虫药进行了全面且批判性的综述，探讨了主要类别以及关于其用于治疗炎症性疾病的现有临床前证据。尽管生物利用度较低，但许多苯并咪唑类药物（阿苯达唑和甲苯达唑）、水杨酰苯胺类药物（氯硝柳胺）、大环内酯类药物（阿维菌素）、吡嗪异喹啉类药物（吡喹酮）、噻唑类药物（硝唑尼特）、哌嗪衍生物以及咪唑并噻唑类药物（左旋咪唑）表明重新利用是一种有前景的策略。它们可能代表着一种成本更低且节省时间的途径，以扩展抗炎选择。尽管作用机制尚未完全阐明和明确，但一般来说，驱虫药会破坏丝裂原活化蛋白激酶、促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、白细胞介素-8、白细胞介素-12和干扰素-γ）的合成、白细胞的迁移和浸润，并降低环氧化酶-2的表达，这会对前列腺素和白三烯的释放产生负面影响。此外，其中一些药物会减少核因子-κB（氯硝柳胺、阿苯达唑和伊维菌素）的核内积累、一氧化氮水平（硝唑尼特和阿苯达唑），以及实验性炎症性肺病中的黏液、细胞因子和支气管收缩（伊维菌素和氯硝柳胺）。考虑到细胞因子、缓激肽、组胺和伤害感受器与疼痛之间的联系，驱虫药在治疗炎症性疼痛疾病（伊维菌素、氯硝柳胺、硝唑尼特、甲苯达唑、左旋咪唑）方面也表现突出，包括癌症相关的疼痛状态。但存在一些障碍，包括生物利用度低和首过代谢。
