Department of Clinical Biochemistry, Faculty of Medicine, King Khalid University, Abha, Saudi Arabia.
Department of Biotechnology, Institute of Graduate Studies and Research (IGSR), Alexandria University, Egypt.
Oxid Med Cell Longev. 2023 Jan 31;2023:9944985. doi: 10.1155/2023/9944985. eCollection 2023.
Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) as in an indirect measure of free radicals. Interestingly, SF-CS NPs and T-SF-CS-NPs treatments significantly attenuated the inhibitory effects of SF on the activity of these enzymes whereas, GST activity was inhibited. Moreover, the protein expression of GST was downregulated upon treatment of rats with free SF, SF-CS-NPs, and T-SF CS-NPs. In contrast, the activity and protein expression of GPx was induced by SF-CS NPs and T-SF-CS-NPs treatments. The histopathological study showed that SF induced multiple adverse effects on the rat liver architecture which were markedly suppressed particularly by T-SF-CS NPs. In conclusion, chitosan nanoencapsulation of SF counteracted the adverse effects of SF on the activity of antioxidant enzymes and liver architecture. Findings might have significant implications in improving the safety and efficacy of SF treatment of the widely expanding disease conditions.
西地那非（SF）被广泛用于治疗勃起功能障碍和其他疾病，但由于口服吸收和不良反应的限制，其应用受到了限制。尽管纳米技术有所改进，但纳米载体对 SF 肝毒性的影响尚未有文献记载。本研究旨在评估未经包被的壳聚糖纳米粒（CS NPs）或聚山梨酯 80 包被的壳聚糖纳米粒（T-CS NPs）对 SF 对大鼠氧化应激标志物和抗氧化酶活性影响的作用。通过离子凝胶化制备的 SF-CS NPs 是均匀带正电的纳米球（直径 178-215nm）。SF 以游离或纳米包封形式（SF-CS NPs 和 T-SF-CS NPs）以 1.5mg/kg 体重的剂量经腹腔注射给予雄性大鼠，持续 3 周。游离 SF 显著抑制了抗氧化酶谷胱甘肽 S-转移酶（GST）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的活性，以及谷胱甘肽（GSH）和硫代巴比妥酸反应物质（TBARS）的水平，这是自由基的间接测量。有趣的是，SF-CS NPs 和 T-SF-CS-NPs 处理显著减弱了 SF 对这些酶活性的抑制作用，而 GST 活性受到抑制。此外，用游离 SF、SF-CS-NPs 和 T-SF CS-NPs 处理大鼠后，GST 的蛋白表达也下调。相比之下，SF-CS NPs 和 T-SF-CS-NPs 处理诱导了 GPx 的活性和蛋白表达。组织病理学研究表明，SF 对大鼠肝组织结构造成多种不良影响，而 T-SF-CS-NPs 则显著抑制了这些影响。总之，SF 的壳聚糖纳米包封抵消了 SF 对抗氧化酶活性和肝组织结构的不良影响。这些发现可能对提高 SF 治疗广泛扩展疾病的安全性和疗效具有重要意义。
