Mansour Heba M, Salama Abeer A A, Abdel-Salam Rania M, Ahmed Naglaa A, Yassen Noha N, Zaki Hala F
a Pharmacology & Toxicology Department, Faculty of Pharmacy, Misr University for Science and Technology, Giza, Egypt.
b Pharmacology Department, National Research Centre, Giza, Egypt.
Can J Physiol Pharmacol. 2018 Dec;96(12):1308-1317. doi: 10.1139/cjpp-2018-0338. Epub 2018 Nov 6.
Liver fibrosis is a health concern that leads to organ failure mediated via production of inflammatory cytokines and fibrotic biomarkers. This study aimed to explore the protective effect of tadalafil, a phosphodiesterase-5 inhibitor, against thioacetamide (TAA)-induced liver fibrosis. Fibrosis was induced by administration of TAA (200 mg/kg, i.p.) twice weekly for 6 weeks. Serum transaminases activities, liver inflammatory cytokines, fibrotic biomarkers, and liver histopathology were assessed. TAA induced marked histopathological changes in liver tissues coupled with elevations in serum transaminases activities. Furthermore, hepatic content of nitric oxide and tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta were elevated, together with a reduction of interleukin-10 in the liver. In addition, TAA increased hepatic contents of transforming growth factor-beta, hydroxyproline, alpha-smooth muscle actin, and gene expression of collagen-1. Pretreatment with tadalafil protected against TAA-induced liver fibrosis, in a dose-dependent manner, as proved by the alleviation of inflammatory and fibrotic biomarkers. The effects of tadalafil were comparable with that of silymarin, a natural antioxidant, and could be assigned to its anti-inflammatory and anti-fibrotic properties.
肝纤维化是一个关乎健康的问题，它通过炎性细胞因子和纤维化生物标志物的产生介导导致器官衰竭。本研究旨在探讨磷酸二酯酶-5抑制剂他达拉非对硫代乙酰胺（TAA）诱导的肝纤维化的保护作用。通过每周两次腹腔注射TAA（200mg/kg），持续6周来诱导纤维化。评估血清转氨酶活性、肝脏炎性细胞因子、纤维化生物标志物和肝脏组织病理学。TAA诱导肝脏组织出现明显的组织病理学变化，同时血清转氨酶活性升高。此外，肝脏中一氧化氮、肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1β的含量升高，同时肝脏中白细胞介素-10减少。另外，TAA增加了肝脏中转化生长因子-β、羟脯氨酸、α-平滑肌肌动蛋白的含量以及胶原蛋白-1的基因表达。他达拉非预处理以剂量依赖的方式预防了TAA诱导的肝纤维化，这通过炎性和纤维化生物标志物的减轻得到证实。他达拉非的作用与天然抗氧化剂水飞蓟宾相当，并且可归因于其抗炎和抗纤维化特性。
