Isoniazid (INH) is among the most important anti-tuberculosis agents widely prescribed. However, its clinical use is restricted due to its severe side effects associated with neurotoxicity. The aim of the present study was to investigate the neuroprotective effects of chrysin (CR), a natural antioxidant, against INH-induced neurotoxicity in rats. The rats were treated orally with INH (400 mg/kg body weight) alone or with CR (25 and 50 mg/kg body weight) for 7 consecutive days. INH administration significantly increased brain lipid peroxidation and resulted in a significant decrease in antioxidant biomarkers including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH). INH treatment also increased levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP) and activities of p38α mitogen-activated protein kinase (p38α MAPK) while decreasing levels of neural cell adhesion molecule (NCAM). Double immunofluorescence expressions of c-Jun N-terminal kinase (JNK) and Bcl-2 associated X protein (Bax) in brain tissues were increased after INH administration. Furthermore, INH increased mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (Gclm), glutamate cysteine ligase catalytic subunit (Gclc), NF-κB, TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6) and GFAP in rat brain tissues. Co-treatment with CR increased anti-oxidant capacity as well as regulated inflammation and apoptosis in brain. Additionally, molecular docking results showed that CR had the potential to interact with the active sites of TNF-α and NFκ-B. In conclusion, CR improved INH-induced brain oxidative damage, inflammation and apoptosis, possibly through their antioxidant properties.

异烟肼 (INH) 是广泛使用的最重要的抗结核药物之一。然而，由于其与神经毒性相关的严重副作用，其临床应用受到限制。本研究的目的是研究白杨素 (CR)（一种天然抗氧化剂）对 INH 诱导的大鼠神经毒性的神经保护作用。大鼠连续口服 INH（400 mg/kg 体重）或 CR（25 和 50 mg/kg 体重）连续 7 天。INH 给药显着增加脑脂质过氧化，并导致抗氧化生物标志物显着减少，包括超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT)、谷胱甘肽过氧化物酶 (GPx) 和谷胱甘肽 (GSH)。INH 治疗还增加了核因子 kappa B (NF-κB)、肿瘤坏死因子-α (TNF-α)、胶质纤维酸性蛋白 (GFAP) 和 p38α 丝裂原活化蛋白激酶 (p38α MAPK) 的活性，同时降低神经细胞粘附分子 (NCAM) 的水平。INH给药后，脑组织中c-Jun N末端激酶（JNK）和Bcl-2相关X蛋白（Bax）的双重免疫荧光表达增加。此外，INH 增加了核因子类红细胞 2 相关因子 2 (Nrf-2)、血红素加氧酶-1 (HO-1)、NAD(P)H：醌氧化还原酶 1 (NQO1)、谷氨酸-半胱氨酸连接酶修饰剂的 mRNA 表达水平亚基 (Gclm)、谷氨酸半胱氨酸连接酶催化亚基 (Gclc)、NF-κB、TNF-α、白介素-1β (IL-1β)、白介素-6 (IL-6) 和大鼠脑组织中的 GFAP。与 CR 共同治疗增加了抗氧化能力，并调节了大脑中的炎症和细胞凋亡。此外，分子对接结果表明，CR 具有与 TNF-α 和 NFκ-B 的活性位点相互作用的潜力。总之，CR 改善了 INH 诱导的脑氧化损伤、炎症和细胞凋亡，可能是通过它们的抗氧化特性。