El Gazzar Walaa Bayoumie, Farag Amina A, Samir Mohamed, Bayoumi Heba, Youssef Heba S, Marei Yasmin Mohammed, Mohamed Shimaa K, Marei Azza M, Abdelfatah Reham M, Mahmoud Manal Moustafa, Aboelkomsan Elshaimaa Ahmed Fahmy, Khalfallah Eman Kamel M, Anwer Hala Magdy
Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan.
Department of Medical Biochemistry and Molecular biology, Faculty of Medicine, Benha University, Benha City, Qalyubia, Egypt.
Biofactors. 2025 Jan-Feb;51(1):e2107. doi: 10.1002/biof.2107. Epub 2024 Jul 29.
Concerns have been expressed about imidacloprid (IMI), one of the most often used pesticides, and its potential neurotoxicity to non-target organisms. Chronic neuroinflammation is central to the pathology of several neurodegenerative disorders. Hence, exploring the molecular mechanism by which IMI would trigger neuroinflammation is particularly important. This study examined the neurotoxic effects of oral administration of IMI (45 mg/kg/day for 30 days) and the potential neuroprotective effect of berberine (Ber) chloride loaded nano-PEGylated liposomes (Ber-Lip) (10 mg/kg, intravenously every other day for 30 days) using laboratory rat. The histopathological changes, anti-oxidant and oxidative stress markers (GSH, SOD, and MDA), proinflammatory cytokines (IL1β and TNF-α), microglia phenotype markers (CD86 and iNOS for M1; CD163 for M2), the canonical pyroptotic pathway markers (NLRP3, caspase-1, GSDMD, and IL-18) and Alzheimer's disease markers (Neprilysin and beta amyloid [Aβ] deposits) were assessed. Oral administration of IMI resulted in apparent cerebellar histopathological alterations, oxidative stress, predominance of M1 microglia phenotype, significantly upregulated NLRP3, caspase-1, GSDMD, IL-18 and Aβ deposits and significantly decreased Neprilysin expression. Berberine reduced the IMI-induced aberrations in the measured parameters and improved the IMI-induced histopathological and ultrastructure alterations brought on by IMI. This study highlights the IMI neurotoxic effect and its potential contribution to the development of Alzheimer's disease and displayed the neuroprotective effect of Ber-Lip.
人们对最常用的杀虫剂之一吡虫啉（IMI）及其对非靶标生物的潜在神经毒性表示担忧。慢性神经炎症是几种神经退行性疾病病理的核心。因此，探索IMI引发神经炎症的分子机制尤为重要。本研究使用实验大鼠，研究了口服IMI（45毫克/千克/天，持续30天）的神经毒性作用以及载有黄连素（Ber）的纳米聚乙二醇化脂质体（Ber-Lip）（10毫克/千克，每隔一天静脉注射，持续30天）的潜在神经保护作用。评估了组织病理学变化、抗氧化和氧化应激标志物（谷胱甘肽、超氧化物歧化酶和丙二醛）、促炎细胞因子（白细胞介素1β和肿瘤坏死因子-α）、小胶质细胞表型标志物（M1型的CD86和诱导型一氧化氮合酶；M2型的CD163）、经典的焦亡途径标志物（NLRP3、半胱天冬酶-1、gasdermin D和白细胞介素-18）以及阿尔茨海默病标志物（中性内肽酶和β淀粉样蛋白[Aβ]沉积）。口服IMI导致明显的小脑组织病理学改变、氧化应激、M1小胶质细胞表型占主导、NLRP3、半胱天冬酶-1、gasdermin D、白细胞介素-18和Aβ沉积显著上调，中性内肽酶表达显著降低。黄连素减少了IMI诱导的测量参数异常，并改善了IMI引起的组织病理学和超微结构改变。本研究突出了IMI的神经毒性作用及其对阿尔茨海默病发展的潜在影响，并展示了Ber-Lip的神经保护作用。
