Mahdavi Arshia, Mahdavifard Sina, Mazani Mohammad
Department of Clinical Biochemistry, Faculty of Medicine, Ardabil University of Medical Sciences, P.O. Box, 56189-85991, Ardabil, Iran.
Department of Biochemistry and Genetics, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep 22. doi: 10.1007/s00210-025-04232-6.
Lead (Pb) induces tissue damage by elevating oxidative stress and activating the nuclear factor-κB (NF-κB) signaling pathway. This study aimed to investigate the effects of pyridoxal phosphate (PLP) on hepatic NF-kβ expression and endogenous antioxidant capacity. Additionally, we evaluated biochemical parameters and histological features of the liver. Forty-four rats were divided into four equal groups: a normal, an untreated lead toxicity rat model (Pbt), and two treated groups receiving PLP at of 90 mg/L and 180 mg/L in their drinking water for one month. Pb intoxication was induced by administrating of 50 mg/L of lead acetate in the drinking water over the same period. Oxidative stress and inflammatory markers were measured in serum and liver homogenates. Additionally, liver biochemical parameters, histological features, and NF-kB expression were also analyzed. PLP demonstrated a dose-dependent protective effect against Pb intoxication. Both lower and higher doses of PLP mitigated liver injury by inhibiting Kupffer cell hyperplasia, which linked to a reduction in the NF-kβ/BACT ratio and an enhancement of antioxidant capacity. The higher dose of PLP also prevented Pb-induced histopathological changes in the liver and exhibited a more pronounced positive effect on liver function. PLP exhibited a dose-dependent protective effect on the liver against Pb poisoning by inhibiting the overgrowth of Kupffer cells and reducing myeloperoxidase (MPO) activity through the regulation of hepatic NF-kB with GSH. Consequently, enhancing the GSH/GSSG ratio and stimulating antioxidant enzymes offers a promising strategy for mitigating Pb toxicity.
铅（Pb）通过提高氧化应激水平和激活核因子-κB（NF-κB）信号通路来诱导组织损伤。本研究旨在探讨磷酸吡哆醛（PLP）对肝脏NF-κB表达和内源性抗氧化能力的影响。此外，我们评估了肝脏的生化参数和组织学特征。44只大鼠被分为四组，每组数量相等：正常组、未经处理的铅中毒大鼠模型组（Pbt）以及两个处理组，这两个处理组大鼠饮用含90 mg/L和180 mg/L PLP的水一个月。同期，通过在饮用水中给予50 mg/L醋酸铅诱导大鼠铅中毒。检测血清和肝脏匀浆中的氧化应激和炎症标志物。此外，还分析了肝脏生化参数、组织学特征和NF-κB表达。PLP对铅中毒表现出剂量依赖性保护作用。较低剂量和较高剂量的PLP均通过抑制库普弗细胞增生减轻肝损伤，这与NF-κB/细菌人工染色体（BACT）比值降低和抗氧化能力增强有关。较高剂量的PLP还可预防铅诱导的肝脏组织病理学变化，对肝功能表现出更明显的积极作用。PLP通过抑制库普弗细胞过度生长以及通过谷胱甘肽（GSH）调节肝脏NF-κB来降低髓过氧化物酶（MPO）活性，从而对肝脏铅中毒表现出剂量依赖性保护作用。因此，提高GSH/氧化型谷胱甘肽（GSSG）比值并刺激抗氧化酶为减轻铅毒性提供了一种有前景的策略。
