Department of Medical Biochemistery and Molecular Biology, Faculty of Medicine, Benha University, Benha, 13518, Egypt.
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, 13736, Qalyubia, Egypt.
Sci Rep. 2024 Jul 23;14(1):16902. doi: 10.1038/s41598-024-67305-1.
The liver carries out many essential tasks, such as synthesising cholesterol, controlling the body's storage of glycogen, and detoxifying metabolites, in addition to performing, and regulating homeostasis. Hepatic fibrosis is a pathological state characterized by over accumulation of extracellular matrix (ECM) including collagen fibers. Sildenafil (a selective inhibitor of type 5 phosphodiesterase) has anti-inflammatory, antioxidant and anti-apoptotic properties. It is commonly used to treat erectile dysfunction in male. The purpose of the current investigation was to evaluate sildenafil's hepatoprotective potential against liver fibrosis in rats that was caused by carbon tetrachloride (CCl). Liver enzymes and oxidative markers as well as profibrotic genes were determined. The findings showed that sildenafil alleviates the hepatic dysfunctions caused by CCl by restoring normal levels of ALT, AST, and GGT as well as by restoring the antioxidant status demonstrated by increased glutathione (GSH), and catalase. In addition, a significantly down-regulated the mRNA expressions of profibrotic genes [collagen-1α, IL-1β, osteopontin (OPN), and transforming growth factor-β (TGF-β)]. Additionally, sildenafil lessens the periportal fibrosis between hepatic lobules, congestion and dilatation in the central vein, and the inflammatory cell infiltrations. As a result, it is hypothesized that sildenafil may be helpful in the management of hepatotoxicity brought on by CCl through suppressing OPN.
肝脏执行许多重要任务，如合成胆固醇、控制体内糖原储存、解毒代谢物，以及发挥和调节体内平衡的作用。肝纤维化是一种病理状态，其特征是细胞外基质（ECM）过度积累，包括胶原纤维。西地那非（一种 5 型磷酸二酯酶的选择性抑制剂）具有抗炎、抗氧化和抗细胞凋亡的特性。它通常用于治疗男性勃起功能障碍。本研究旨在评估西地那非对四氯化碳（CCl）引起的大鼠肝纤维化的潜在保护作用。测定了肝酶和氧化标志物以及促纤维化基因。结果表明，西地那非通过恢复 ALT、AST 和 GGT 的正常水平以及通过增加谷胱甘肽（GSH）和过氧化氢酶来恢复抗氧化状态，从而缓解 CCl 引起的肝功能障碍。此外，显著下调了促纤维化基因[胶原-1α、IL-1β、骨桥蛋白（OPN）和转化生长因子-β（TGF-β）]的 mRNA 表达。此外，西地那非减轻了肝小叶间的门脉周围纤维化、中央静脉充血和扩张以及炎症细胞浸润。因此，研究假设西地那非可能通过抑制 OPN 有助于 CCl 引起的肝毒性的管理。
