Deulofeu R, Parés A, Rubio M, Gassó M, Román J, Giménez A, Varela-Moreiras G, Caballeria J, Ballesta A M, Mato J M, Rodés J
Laboratory of Biochemistry, Hospital Clínic i Provincial, University of Barcelona, Barcelona, Spain.
Clin Sci (Lond). 2000 Oct;99(4):315-20.
In various experimental models, S-adenosylmethionine (SAMe) has been shown to reduce liver injury by preventing depletion of glutathione, one of the antioxidant systems that plays a critical role in defence against oxidative stress. On the other hand, alpha-tocopherol may be decreased in liver diseases, and treatment with this vitamin reduces liver injury in CCl(4)-treated rats. Since there is a close relationship among the different antioxidant systems (mainly glutathione, alpha-tocopherol and ascorbic acid), we have assessed whether, as well as restoring hepatic glutathione content, SAMe has any effect on liver alpha-tocopherol and ascorbic acid levels in CCl(4)-injured rats. Four groups of seven male Wistar rats treated for 9 weeks were studied: rats induced to cirrhosis with CCl(4), rats induced to cirrhosis plus SAMe administration (10 mg x kg(-1) x day(-1)) and their respective controls. Liver samples were obtained for measuring levels of glutathione, alpha-tocopherol, ascorbic acid and thiobarbituric acid-reactive substances (TBARS), and hydroxyproline concentration as an index of collagen content. The hydroxyproline content was higher in CCl(4)-injured rats than in the control group (4.4+/-1.8 and 1.1+/-0.3 micromol/g respectively; P<0.05). In CCl(4)-injured rats, SAMe administration decreased collagen content (2.7+/-1.0 microl/g; P<0.05) and TBARS, and corrected glutathione depletion. alpha-Tocopherol was significantly lower in CCl(4)-injured rats than in controls (17.3+/-4.9 and 23.0+/-4.0 micromol/g respectively; P<0.05). By contrast, alpha-tocopherol levels were similar (23.8+/-5.1 micromol/g) in CCl(4)-injured rats receiving SAMe and in controls. In CCl(4)-injured rats, liver ascorbic acid was decreased in comparison with controls (4.9+/-1.8 and 8.2+/-1.0 micromol/g respectively; P<0.05), levels which were not replenished by SAMe (4.6+/-0.4 micromol/g). In conclusion, SAMe not only decreases fibrosis and protects against hepatic glutathione depletion, but has a further antioxidant effect of preventing alpha-tocopherol depletion in CCl(4)-injured rats.
在各种实验模型中，已表明S-腺苷甲硫氨酸（SAMe）可通过防止谷胱甘肽耗竭来减轻肝损伤，谷胱甘肽是抗氧化系统之一，在抵御氧化应激中起关键作用。另一方面，肝脏疾病时α-生育酚水平可能降低，用这种维生素进行治疗可减轻四氯化碳处理大鼠的肝损伤。由于不同抗氧化系统（主要是谷胱甘肽、α-生育酚和抗坏血酸）之间存在密切关系，我们评估了SAMe除了恢复肝脏谷胱甘肽含量外，对四氯化碳损伤大鼠肝脏中的α-生育酚和抗坏血酸水平是否有影响。研究了四组每组七只雄性Wistar大鼠，处理9周：用四氯化碳诱导肝硬化的大鼠、用四氯化碳诱导肝硬化加给予SAMe（10mg·kg⁻¹·天⁻¹）的大鼠及其各自的对照组。获取肝脏样本以测量谷胱甘肽、α-生育酚、抗坏血酸和硫代巴比妥酸反应性物质（TBARS）的水平，以及作为胶原含量指标的羟脯氨酸浓度。四氯化碳损伤大鼠的羟脯氨酸含量高于对照组（分别为4.4±1.8和1.1±0.3微摩尔/克；P<0.05）。在四氯化碳损伤大鼠中，给予SAMe可降低胶原含量（2.7±1.0微克/克；P<0.05）和TBARS，并纠正谷胱甘肽耗竭。四氯化碳损伤大鼠的α-生育酚显著低于对照组（分别为17.3±4.9和23.0±4.0微摩尔/克；P<0.05）。相比之下，接受SAMe的四氯化碳损伤大鼠的α-生育酚水平与对照组相似（23.8±5.1微摩尔/克）。在四氯化碳损伤大鼠中，肝脏抗坏血酸与对照组相比降低（分别为4.9±1.8和8.2±1.0微摩尔/克；P<0.05），SAMe未使其水平得到补充（4.6±0.4微摩尔/克）。总之，SAMe不仅可减少纤维化并防止肝脏谷胱甘肽耗竭，而且在四氯化碳损伤大鼠中还有防止α-生育酚耗竭的进一步抗氧化作用。
