Biochemistry and Molecular Biology Department, Faculty of Veterinary Medicine, Benha University, Egypt.
Health Radiation Research, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Int J Immunopathol Pharmacol. 2024 Jan-Dec;38:3946320241272642. doi: 10.1177/03946320241272642.
Prolonged exposure to different occupational or environmental toxicants triggered oxidative stress and inflammatory reactions mediated lung damage. This study was designed to explore the influence and protective impact of flavone on lung injury in rats intoxicated with nicotine (NIC) and exposed to radiation (IR). Forty rats were divided into four groups; group I control, group II flavone; rats were administered with flavone (25 mg/kg/day), group III NIC + IR; rats were injected intraperitoneally with NIC (1 mg/kg/day) and exposed to γ-IR (3.5 Gy once/week for 2 weeks) while group IV NIC + IR + flavone; rats were injected with NIC, exposed to IR and administered with flavone. Redox status parameters and histopathological changes in lung tissue were evaluated. Nuclear factor-kappa B (NF-κB), forkhead box O-class1 (FoxO1) and nucleotide-binding domain- (NOD-) like receptor pyrin domain-containing-3 (NLRP3) gene expression were measured in lung tissues. Moreover, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and phosphatidylinositol three kinase (PI3K) were measured using ELISA kits. Our data demonstrates, for the first time, that flavone protects the lung from NIC/IR-associated cytotoxicity, by attenuating the disrupted redox status and aggravating the antioxidant defence mechanism via activation of the PI3K/Nrf2. Moreover, flavone alleviates pulmonary inflammation by inhibiting the inflammatory signaling pathway FOXO1/NF-κB/NLRP3- Inflammasome. Collectively, the obtained results exhibited a notable efficiency of flavone in alleviating lung injury induced by NIC and IR via modulating PI3K/Nrf2 and FoxO1/NLRP3 Inflammasome.
长期接触不同的职业或环境毒物会引发氧化应激和炎症反应，导致肺部损伤。本研究旨在探讨黄酮类化合物对尼古丁（NIC）中毒和辐射（IR）暴露大鼠肺损伤的影响和保护作用。将 40 只大鼠分为四组；第 I 组为对照组，第 II 组为黄酮组；大鼠给予黄酮（25mg/kg/天），第 III 组为 NIC+IR 组；大鼠腹腔注射 NIC（1mg/kg/天），每周接受 γ-IR（3.5Gy 一次），共 2 周，第 IV 组为 NIC+IR+黄酮组；大鼠注射 NIC，暴露于 IR 并给予黄酮。评估肺组织氧化还原状态参数和组织病理学变化。测量肺组织中核因子-κB（NF-κB）、叉头框 O 类 1（FoxO1）和核苷酸结合域-（NOD-）样受体吡啶结构域包含 3（NLRP3）基因表达。此外，还使用 ELISA 试剂盒测量核因子（红系衍生 2）样 2（Nrf2）和磷脂酰肌醇三激酶（PI3K）。我们的数据首次表明，黄酮类化合物通过激活 PI3K/Nrf2 来减轻氧化还原状态的破坏并加重抗氧化防御机制，从而保护肺免受 NIC/IR 相关细胞毒性。此外，黄酮类化合物通过抑制炎症信号通路 FOXO1/NF-κB/NLRP3-炎症小体来减轻肺部炎症。总之，研究结果表明，黄酮类化合物通过调节 PI3K/Nrf2 和 FoxO1/NLRP3 炎症小体，在减轻 NIC 和 IR 诱导的肺损伤方面具有显著的效果。
