Department of Parasitology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt.
Department of Histology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt.
Parasitol Res. 2023 Dec 18;123(1):57. doi: 10.1007/s00436-023-08077-x.
Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis.
旋毛虫病是一种全球性食源性寄生虫病,可导致严重的组织损伤。传统上用于治疗旋毛虫病的药物对疾病肌肉期的囊包幼虫疗效有限。因此,本研究旨在评估阿托伐他汀和间充质干细胞联合伊维菌素对实验感染小鼠旋毛虫不同阶段的作用。总共将 120 只雄性瑞士白化病小鼠分为两个主要组(每组 60 只),即肠道期和肌肉期。然后,每个组进一步分为 10 个亚组(每组 6 只);未感染对照、未感染未治疗对照、感染伊维菌素治疗、感染阿托伐他汀治疗、感染间充质干细胞治疗、感染联合伊维菌素和阿托伐他汀治疗、感染联合间充质干细胞和伊维菌素治疗、感染联合间充质干细胞和阿托伐他汀治疗、感染联合间充质干细胞和全剂量(伊维菌素和阿托伐他汀)治疗、感染联合间充质干细胞和半剂量(伊维菌素和阿托伐他汀)治疗。感染后第 5 天和第 35 天分别对肠道期和肌肉期的小鼠进行处死。通过多种参数进行评估,包括计数肠道成虫和肌肉囊包幼虫,以及对潜在组织进行组织病理学检查。此外,还进行了炎症和氧化应激标志物水平的生化分析。此外,还研究了肌肉期作为血管生成标志物的免疫组化 CD31 和 VEGF 基因表达水平。联合伊维菌素的间充质干细胞和阿托伐他汀显示出对成虫和囊包幼虫计数的最大显著减少,对组织病理学变化的最显著改善,最强的抗炎(最低 IL-17 水平)和抗血管生成(最低 CD31 和 VEGF 表达)作用,并且还显示出缓解氧化应激(最低 SOD、GSH 和脂质过氧化物酶水平)的高效性。这些观察结果表明,联合间充质干细胞和阿托伐他汀可增强伊维菌素的治疗效果,为旋毛虫病提供了一种有前途的治疗候选药物。