Ming Zhi, Fan Yi-jun, Yang Xi, Lautt W Wayne
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3.
Free Radic Biol Med. 2006 Feb 15;40(4):617-24. doi: 10.1016/j.freeradbiomed.2005.09.034. Epub 2005 Oct 19.
Free radicals are involved in the pathogenesis of acute liver injury induced by thioacetamide (TAA). We investigated the effects of S-adenosylmethionine (SAMe) combined with/without vitamins C and E on TAA-induced acute liver injury in rats. TAA was given intraperitoneally (200 mg kg-1). Antioxidant treatments (SAMe, 25 mg kg-1; vitamin C, 100 mg kg-1; vitamin E, 200 mg kg-1, intraperitoneal) were given 1 h later. Liver histology, enzymology, and ability to release hepatic insulin-sensitizing substance (HISS) were assessed. TAA caused liver tissue injury, increased liver enzymes, and decreased insulin sensitivity (p<0.01). Blockade of HISS release by atropine did not further decrease insulin sensitivity in rats with TAA insult, indicating that the decrease in insulin sensitivity was HISS dependent. Treatment with SAMe alone or vitamins C+E slightly improved liver histology but not the changes in liver enzymes and insulin sensitivity. Combined treatment with SAMe plus vitamins C+E greatly protected the liver from tissue injury, the increase in liver enzymes, and the decrease in insulin sensitivity. In conclusion, acute liver injury causes HISS-dependent insulin resistance (HDIR). There are synergistic antioxidative effects among the antioxidants, SAMe and vitamins C and E, that protect the liver from TAA-induced HDIR, suggesting that antioxidant treatment may best be done using a balanced "cocktail."
自由基参与硫代乙酰胺（TAA）诱导的急性肝损伤的发病机制。我们研究了S-腺苷甲硫氨酸（SAMe）联合/不联合维生素C和E对TAA诱导的大鼠急性肝损伤的影响。腹腔注射TAA（200 mg kg-1）。1小时后给予抗氧化治疗（SAMe，25 mg kg-1；维生素C，100 mg kg-1；维生素E，200 mg kg-1，腹腔注射）。评估肝脏组织学、酶学以及释放肝脏胰岛素增敏物质（HISS）的能力。TAA导致肝组织损伤、肝酶升高以及胰岛素敏感性降低（p<0.01）。阿托品阻断HISS释放并未进一步降低遭受TAA损伤大鼠的胰岛素敏感性，表明胰岛素敏感性降低是HISS依赖性的。单独使用SAMe或维生素C+E治疗可轻微改善肝脏组织学，但不能改善肝酶和胰岛素敏感性的变化。SAMe联合维生素C+E治疗可极大地保护肝脏免受组织损伤、肝酶升高以及胰岛素敏感性降低的影响。总之，急性肝损伤导致HISS依赖性胰岛素抵抗（HDIR）。抗氧化剂SAMe以及维生素C和E之间存在协同抗氧化作用，可保护肝脏免受TAA诱导的HDIR，这表明使用均衡的“鸡尾酒”进行抗氧化治疗可能效果最佳。
