Elsharkawy Amal M, Hassanein Faika, Abouelkheir Samia S, Masoud Inas M, Felefel Wael, Darwish Inas E
Faculty of Medicine, Department of Clinical Pharmacology, Alexandria University, Alexandria, Egypt.
Faculty of Dentistry, Department of Microbiology and Immunology, Pharos University in Alexandria, Alexandria, Egypt.
PLoS One. 2025 Jun 3;20(6):e0324191. doi: 10.1371/journal.pone.0324191. eCollection 2025.
Alzheimer's disease, affecting 7.24 million globally, requires combination therapies, including cholinesterase inhibitors and immunotherapy, for optimal management, emphasizing the benefits of these treatments. The current study investigated the potential synergy between superparamagnetic iron oxide nanoparticles (SPIONs) and a soluble product of Dipylidium caninum adult worms to enhance biochemical and cognitive changes in a colchicine-induced rat model of Alzheimer's disease. The study involved 50 male albino rats randomly assigned into five groups: group I, the negative control; group II, the positive control; group III, the soluble product of D. caninum excretory-secretory product (ESP)-intervened group; group IV, the SPION-intervened group; and group V, the combination of SPIONs and the soluble product of D. caninum adult worm ESP-intervened group. Each group consisted of 10 rats. The study compared the biochemical and cognitive abilities of the three intervention groups to the negative control using the MANOVA test, revealing a significant fit model (p = 0.000) and a large effect size (partial eta squared = 0.750) for the biochemical improvement. The same results were found for all biochemical tests, including amyloid beta (AB1-42), nuclear factor-kappa B (NF-kB), malondialdehyde (MDA), and superoxide dismutase (SOD). The effect sizes were large (0.551, 0.729, 0.674, and 0.445, respectively), and the fit models were significant (P = 0.000). When comparing the experimental groups pairwise, it was clear that group V was the most effective therapy, as it had the smallest mean difference across all biochemical markers when compared to the negative control group. Regarding cognitive changes, both the multivariate test and tests of between-subject effects of all seven cognitive parameters were significant, with P values ≤ 0.05 and a large effect size due to the partial eta squared values above 0.1. However, for the passive avoidance (PA) effect, initial latency and locomotor activity have medium effect sizes with values between 0.01 and 0.1 (0.061 and 0.018, respectively). Pairwise comparisons between intervention and negative control groups revealed that group IV (SPION-intervened) had the smallest values of cognitive parameters, making it the best intervention therapy for cognitive changes. The Log Rank (Mantel-Cox) Kaplan-Meier curve indicated that the least mean timing needed for cognitive changes to normalize was 20 days at a median point of 0.5, with group III (D. caninum ESP-intervened group) having a significantly different Log Rank (Chi-Square = 85.490, P = 0.000).
阿尔茨海默病全球患者达724万，需要联合治疗，包括胆碱酯酶抑制剂和免疫疗法，以实现最佳管理，这些治疗方法的益处显著。本研究调查了超顺磁性氧化铁纳米颗粒（SPIONs）与犬复孔绦虫成虫可溶性产物之间的潜在协同作用，以增强秋水仙碱诱导的阿尔茨海默病大鼠模型中的生化和认知变化。该研究涉及50只雄性白化大鼠，随机分为五组：第一组为阴性对照组；第二组为阳性对照组；第三组为犬复孔绦虫排泄分泌产物（ESP）干预组；第四组为SPION干预组；第五组为SPIONs与犬复孔绦虫成虫ESP可溶性产物联合干预组。每组10只大鼠。该研究使用多变量方差分析（MANOVA）检验将三个干预组的生化和认知能力与阴性对照组进行比较，结果显示生化改善方面有显著的拟合模型（p = 0.000）和较大的效应量（偏 eta 平方 = 0.750）。所有生化检测结果均相同，包括β淀粉样蛋白（AB1 - 42）、核因子κB（NF - kB）、丙二醛（MDA）和超氧化物歧化酶（SOD）。效应量较大（分别为0.551、0.729、0.674和0.445），拟合模型显著（P = 0.000）。两两比较实验组时，很明显第五组是最有效的治疗组，因为与阴性对照组相比，其所有生化标志物的平均差异最小。关于认知变化，多变量检验以及所有七个认知参数的组间效应检验均显著，P值≤0.05，且由于偏 eta 平方值高于0.1，效应量较大。然而，对于被动回避（PA）效应，初始潜伏期和运动活动的效应量中等，值在0.01至0.1之间（分别为0.061和0.018）。干预组与阴性对照组的两两比较显示，第四组（SPION干预组）的认知参数值最小，使其成为认知变化的最佳干预疗法。对数秩（Mantel - Cox）卡普兰 - 迈耶曲线表明，认知变化恢复正常所需的最短平均时间在中位数0.5时为20天，第三组（犬复孔绦虫ESP干预组）的对数秩有显著差异（卡方 = 85.490，P = 0.000）。
