Department of Clinical Laboratory Sciences, Turabah University College, Taif University, Taif 21944, Saudi Arabia.
Department of Basic Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O Box 84428, Riyadh 11671, Saudi Arabia.
Toxicology. 2024 Aug;506:153869. doi: 10.1016/j.tox.2024.153869. Epub 2024 Jun 21.
Exposure to acrylic amide (AD) has garnered worldwide attention due to its potential adverse health effects, prompting calls from the World Health Organization for intensified research into associated risks. Despite this, the relationship between oral acrylic amide (acrylamide) (AD) exposure and pulmonary dysfunction remains poorly understood. Our study aimed to investigate the correlation between internal oral exposure to AD and the decline in lung function, while exploring potential mediating factors such as tissue inflammation, oxidative stress, pyroptosis, and apoptosis. Additionally, we aimed to evaluate the potential protective effect of zinc oxide nanoparticles green-synthesized moringa extract (ZNO-MONPs) (10 mg/kg b.wt) against ACR toxicity and conducted comprehensive miRNA expression profiling to uncover novel targets and mechanisms of AD toxicity (miRNA 223-3 P and miRNA 325-3 P). Furthermore, we employed computational techniques to predict the interactions between acrylic amide and/or MO-extract components and tissue proteins. Using a rat model, we exposed animals to oral acrylamide (20 mg/kg b.wt for 2 months). Our findings revealed that AD significantly downregulated the expression of miRNA 223-3 P and miRNA 325-3 P, targeting NLRP-3 & GSDMD, respectively, indicating the induction of pyroptosis in pulmonary tissue via an inflammasome activating pathway. Moreover, AD exposure resulted in lipid peroxidative damage and reduced levels of GPX, CAT, GSH, and GSSG. Notably, AD exposure upregulated apoptotic, pyroptotic, and inflammatory genes, accompanied by histopathological damage in lung tissue. Immunohistochemical and immunofluorescence techniques detected elevated levels of indicative harmful proteins including vimentin and 4HNE. Conversely, concurrent administration of ZNO-MONPs with AD significantly elevated the expression of miRNA 223-3 P and miRNA 325-3 P, protecting against oxidative stress, apoptosis, pyroptosis, inflammation, and fibrosis in rat lungs. In conclusion, our study highlights the efficacy of ZNO-MONPs NPs in protecting pulmonary tissue against the detrimental impacts of foodborne toxin AD.
丙烯酰胺（AD）的暴露引起了全球关注，因为它可能对健康造成不良影响，世界卫生组织呼吁加强对相关风险的研究。尽管如此，口腔丙烯酰胺（丙烯酰胺）（AD）暴露与肺功能障碍之间的关系仍知之甚少。我们的研究旨在调查内部口腔 AD 暴露与肺功能下降之间的相关性，同时探索组织炎症、氧化应激、细胞焦亡和细胞凋亡等潜在的中介因素。此外，我们还评估了氧化锌纳米粒子绿色合成辣木叶提取物（ZNO-MONPs）（10mg/kg b.wt）对 ACR 毒性的潜在保护作用，并进行了全面的 miRNA 表达谱分析，以揭示 AD 毒性的新靶点和机制（miRNA 223-3P 和 miRNA 325-3P）。此外，我们还采用计算技术预测丙烯酰胺和/或 MO 提取物成分与组织蛋白之间的相互作用。我们使用大鼠模型，使动物口服丙烯酰胺（20mg/kg b.wt 持续 2 个月）。我们的研究结果表明，AD 显著下调了 miRNA 223-3P 和 miRNA 325-3P 的表达，分别靶向 NLRP-3 和 GSDMD，表明通过炎性体激活途径诱导肺组织细胞焦亡。此外，AD 暴露导致脂质过氧化损伤和 GPX、CAT、GSH 和 GSSG 水平降低。值得注意的是，AD 暴露上调了凋亡、细胞焦亡和炎症基因，并伴有肺组织的组织病理学损伤。免疫组织化学和免疫荧光技术检测到包括波形蛋白和 4HNE 在内的指示性有害蛋白水平升高。相反，AD 与 ZNO-MONPs 同时给药可显著上调 miRNA 223-3P 和 miRNA 325-3P 的表达，从而保护大鼠肺部免受食物源毒素 AD 的氧化应激、凋亡、细胞焦亡、炎症和纤维化的影响。综上所述，我们的研究强调了 ZNO-MONPs NPs 保护肺部组织免受食物源性毒素 AD 有害影响的功效。
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