Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Biomed Pharmacother. 2017 May;89:98-107. doi: 10.1016/j.biopha.2017.02.010. Epub 2017 Feb 20.
Liver fibrosis is a common pathological condition that occurs in most conditions associated with chronic liver injury. Silymarin is a herbal product widely used for its hepatoprotective effect. Sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4-I), is clinically used as an oral antidiabetic agent. This study was designed to investigate the effects of Sitagliptin, Silymarin, and their combination on established liver fibrosis in carbon tetrachloride (CCl) rat model. Male albino rats received intraperitoneal injections of CCl three times a week for 7 weeks, as well as daily oral treatments of Sitagliptin (100mg/kg) or Silymarin (100mg/kg) or their combination during the 7 weeks of intoxication. Hepatic fibrotic changes were evaluated by measuring hepatic enzymes (ALT, AST, ALP, and GGT) and markers of fibrosis (transforming growth factor β1 (TGF-β1), tissue 4-hydroxyproline level, histopathological score), oxidative stress (MDA, GSH, and NOx levels), inflammation (interleukin-6) as well as markers of HSCs activation (α-smooth muscle actin (α-SMA) expression). The injected rats with CCl for 7 weeks resulted in a marked elevation of hepatic fibrotic changes and reduction of GSH level, while the combination therapy showed a significant decrease in the former one and a significant increase in the later. In conclusion, this study shows that the combination therapy is more beneficial than monotherapy in ameliorating liver fibrosis in rats. Our findings suggest that Sitagliptin alone or in combination with Silymarin may introduce a new strategy for treating liver fibrosis in humans.
肝纤维化是一种常见的病理状态，发生在大多数与慢性肝损伤相关的情况下。水飞蓟素是一种广泛用于其肝保护作用的草药产品。西他列汀是一种二肽基肽酶-4 抑制剂（DPP4-I），临床上用作口服抗糖尿病药物。本研究旨在探讨西他列汀、水飞蓟素及其联合应用对四氯化碳（CCl）大鼠模型中已建立的肝纤维化的影响。雄性白化大鼠每周腹腔注射 CCl 三次，共 7 周，并在 7 周中毒期间每天口服西他列汀（100mg/kg）或水飞蓟素（100mg/kg）或两者联合治疗。通过测量肝酶（ALT、AST、ALP 和 GGT）和纤维化标志物（转化生长因子β1（TGF-β1）、组织 4-羟脯氨酸水平、组织病理学评分）、氧化应激（MDA、GSH 和 NOx 水平）、炎症（白细胞介素-6）以及 HSCs 激活标志物（α-平滑肌肌动蛋白（α-SMA）表达）来评估肝纤维化变化。注射 CCl 7 周的大鼠肝纤维化明显升高，GSH 水平降低，而联合治疗组前者明显降低，后者明显升高。综上所述，本研究表明，联合治疗比单独治疗更有利于改善大鼠肝纤维化。我们的研究结果表明，西他列汀单独或与水飞蓟素联合使用可能为治疗人类肝纤维化提供一种新策略。
