Clinic for Gastroenterology, Clinical Center Niš, 18000, Niš, Serbia.
Department of Internal Medicine, Faculty of Medicine, University of Niš, Zorana Đinđića 81, 18000, Niš, Serbia.
Amino Acids. 2019 May;51(5):795-803. doi: 10.1007/s00726-019-02716-3. Epub 2019 Mar 16.
We aimed to evaluate whether two methionine-related compounds, S-adenosylmethionine (SAM), and selenomethionine (SM), could lessen liver damage induced by regurgitated bile in a model of rat bile duct ligation (BDL). Hepatoprotective potentials of S-adenosylmethionine and selenomethionine were estimated based on the changes of serum liver damage parameters (aminotransferases, alkaline phosphatase, gamma-glutamyltranspeptidase and lactate dehydrogenase activity, and bilirubin concentration), tissue oxidative [xanthine oxidase (XO) and catalase activity, thiobarbituric acid reactive substances (TBARS) levels] and inflammatory [tumor necrosis factor-alfa (TNF-α) concentration] parameters, and morphological liver tissue alterations that follow cholestasis. The treatment regimens proved themselves able to prevent significant liver damage induced by cholestasis. Both SAM and SM decreased XO activity and TBARS levels and increased catalase activity, while only SM significantly reduced TNF-α concentration. Morphological changes related to bile-induced liver damage were also found to be partially diminished by SAM and SM. In view of the mechanisms of action of the two tested methionine-derived compounds, one might say that SM predominantly acted as an antioxidant, while SAM exerted its activity by potentially modulating different gene expression and protein structures. It is also worth mentioning that this is the first study (to the best of our knowledge) that dealt with the effects of SM on BDL-induced liver injury in rats and of the findings that speak favorably of this powerful antioxidant.
我们旨在评估两种蛋氨酸相关化合物，S-腺苷蛋氨酸（SAM）和硒蛋氨酸（SM），是否可以减轻胆肠吻合术（BDL）模型中胆汁反流引起的肝损伤。根据血清肝损伤参数（转氨酶、碱性磷酸酶、γ-谷氨酰转肽酶和乳酸脱氢酶活性以及胆红素浓度）、组织氧化[黄嘌呤氧化酶（XO）和过氧化氢酶活性、硫代巴比妥酸反应物质（TBARS）水平]和炎症[肿瘤坏死因子-α（TNF-α）浓度]参数以及胆汁淤积后肝组织形态学改变，评估 S-腺苷蛋氨酸和硒蛋氨酸的肝保护潜力。治疗方案证明能够预防由胆汁淤积引起的显著肝损伤。SAM 和 SM 均降低了 XO 活性和 TBARS 水平，并增加了过氧化氢酶活性，而只有 SM 显著降低了 TNF-α 浓度。SAM 和 SM 还部分减轻了与胆汁诱导的肝损伤相关的形态学变化。鉴于两种测试的蛋氨酸衍生化合物的作用机制，可以说 SM 主要作为抗氧化剂发挥作用，而 SAM 通过潜在调节不同基因表达和蛋白质结构发挥其活性。值得一提的是，这是第一项（据我们所知）研究 SM 对 BDL 诱导的大鼠肝损伤的影响，以及支持这种强大的抗氧化剂的发现。
