Fipronil (FIP) insecticide is extensively used in agriculture, public health and veterinary medicine. Although it is considered as a neurotoxin to insects (target organisms) and exhibits neurological signs upon vertebrates (non-target organisms) exposure, slight is known about its potential neurotoxic effects and its molecular mechanisms on vertebrates. The current study is designed to assess oxidative stress as a molecular mechanism of FIP neurotoxicity subordinated with apoptosis and neural tissue reactivity. Ten adult male albino rats received 10 mg/kg body weight fipronil technical grade by oral gavage daily for 45 days (subacute exposure). Brain neural tissue regions (hippocampus, cerebellum and caudate putamen) were processed to examine oxidative stress induced cellular macromolecular alterations as MDA, PCC and DNA fragmentation. Besides, TNF-α and Bcl-2 gene expression and immunoreactivity for caspase-3 (active form), iNOS and GFAP were evaluated. Also, histopathological assessment was conducted. We found that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). Also, it significantly upregulated TNF-α and non-significantly down-regulated Bcl-2 gene expression (p ≤ 0.05). Further, significant increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in these brain neural tissue regions in FIP treated group was noticed (p ≤ 0.05). Histopathological findings, including alterations in the histological architecture and neuronal degeneration, were also observed in these brain regions of FIP treated group. In conclusion, we suggest the ability of FIP to induce oxidative stress mediated macromolecular alterations, leading to apoptosis and tissue reaction in these brain regions which showed variable susceptibility to FIP toxic effects.

氟虫腈 (FIP) 杀虫剂广泛用于农业、公共卫生和兽医领域。尽管它被认为是昆虫（目标生物）的神经毒素，并且在接触脊椎动物（非目标生物）时表现出神经症状，但对其潜在的神经毒性作用及其对脊椎动物的分子机制知之甚少。目前的研究旨在评估氧化应激作为 FIP 神经毒性的分子机制，从属于细胞凋亡和神经组织反应性。10 只成年雄性白化病大鼠每天通过口服管饲法接受 10 mg/kg 体重氟虫腈，持续 45 天（亚急性暴露）。处理脑神经组织区域（海马、小脑和尾状壳核）以检查氧化应激诱导的细胞大分子改变，如 MDA、PCC 和 DNA 片段化。除了，评估了 caspase-3（活性形式）、iNOS 和 GFAP 的 TNF-α 和 Bcl-2 基因表达和免疫反应性。此外，还进行了组织病理学评估。我们发现 FIP 显着提高了 MDA、PCC 和 DNA 片段化 (p ≤ 0.05)。此外，它显着上调 TNF-α 和非显着下调 Bcl-2 基因表达（p ≤ 0.05）。此外，在 FIP 治疗组的这些脑神经组织区域中，注意到对 GFAP、iNOS 和 caspase-3（活性形式）的免疫反应性显着增加（p ≤ 0.05）。在 FIP 治疗组的这些脑区也观察到组织病理学发现，包括组织学结构和神经元变性的改变。总之，我们建议 FIP 能够诱导氧化应激介导的大分子改变，