Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Department of Chemistry, College of Science, Jouf University, Sakaka 2014, Saudi Arabia.
Int J Mol Sci. 2024 May 20;25(10):5562. doi: 10.3390/ijms25105562.
Lead (Pb) is a common pollutant that is not biodegradable and gravely endangers the environment and human health. fruit has a wide range of medicinal uses owing to its phytochemical constituents. This study evaluated the effect of treatment with fruit extract (ASFE) on testicular toxicity induced in male rats by lead acetate. The metal-chelating capacity and phytochemical composition of ASFE were determined. The LD of ASFE was evaluated by probit analysis. Molecular docking simulations were performed using Auto Dock Vina. Forty male Sprague Dawley rats were equally divided into the following groups: Gp1, a negative control group; Gp2, given ASFE (350 mg/kg body weight (b. wt.)) (1/10 of LD); Gp3, given lead acetate (PbAc) solution (100 mg/kg b. wt.); and Gp4, given PbAc as in Gp3 and ASFE as in Gp2. All treatments were given by oro-gastric intubation daily for 30 days. Body weight changes, spermatological parameters, reproductive hormone levels, oxidative stress parameters, and inflammatory biomarkers were evaluated, and molecular and histopathological investigations were performed. The results showed that ASFE had promising metal-chelating activity and phytochemical composition. The LD of ASFE was 3500 mg/kg b. wt. The docking analysis showed that quercetin demonstrated a high binding affinity for JAK-1 and STAT-3 proteins, and this could make it a more promising candidate for targeting the JAK-1/STAT-3 pathway than others. The rats given lead acetate had defective testicular tissues, with altered molecular, biochemical, and histological features, as well as impaired spermatological characteristics. Treatment with ASFE led to a significant mitigation of these dysfunctions and modulated the JAK-1/STAT-3/SOCS-1 axis in the rats.
铅(Pb)是一种常见的污染物,不可生物降解,严重危害环境和人类健康。 水果因其植物化学成分而具有广泛的药用用途。本研究评估了用 水果提取物(ASFE)处理醋酸铅诱导的雄性大鼠睾丸毒性的效果。测定了 ASFE 的金属螯合能力和植物化学成分。通过概率分析评估 ASFE 的 LD。使用 Auto Dock Vina 进行分子对接模拟。40 只雄性 Sprague Dawley 大鼠等分为以下几组:Gp1,阴性对照组;Gp2,给予 ASFE(350mg/kg 体重(b.wt.))(LD 的 1/10);Gp3,给予醋酸铅(PbAc)溶液(100mg/kg b.wt.);Gp4,如 Gp3 中给予 PbAc,如 Gp2 中给予 ASFE。所有治疗均通过口腔灌胃每日进行 30 天。评估体重变化、精子参数、生殖激素水平、氧化应激参数和炎症生物标志物,并进行分子和组织病理学研究。结果表明,ASFE 具有良好的金属螯合活性和植物化学成分。ASFE 的 LD 为 3500mg/kg b.wt.。对接分析表明,槲皮素对 JAK-1 和 STAT-3 蛋白表现出高结合亲和力,这使其成为比其他蛋白更有前途的靶向 JAK-1/STAT-3 途径的候选药物。给予醋酸铅的大鼠睾丸组织受损,分子、生化和组织学特征改变,精子发生特征受损。ASFE 治疗可显著减轻这些功能障碍,并调节大鼠的 JAK-1/STAT-3/SOCS-1 轴。