Feo F, Pascale R, Garcea R, Daino L, Pirisi L, Frassetto S, Ruggiu M E, Di Padova C, Stramentinoli G
Toxicol Appl Pharmacol. 1986 Apr;83(2):331-41. doi: 10.1016/0041-008x(86)90310-8.
The protective effect of S-adenosyl-L-methionine against rat liver steatosis induced by chronic ethanol ingestion was investigated. S-Adenosyl-L-methionine given during ethanol treatment prevented steatosis and accelerated recovery from steatosis when given after ethanol withdrawal. It also caused a slight inhibition of blood ethanol consumption in both acutely and chronically intoxicated rats. About 30% inhibition of alcohol dehydrogenase, but not of the microsomal ethanol oxidation system, occurred in rats subjected to acute ethanol toxicity as well as in normal rats as a consequence of S-adenosyl-L-methionine treatment. A comparison between S-adenosyl-L-methionine and pyrazole, as concerns inhibition of ethanol oxidation and fat accumulation, revealed that a greater inhibition of ethanol metabolism by pyrazole was associated with incomplete prevention of steatosis, while a lower inhibition by S-adenosyl-L-methionine was coupled to a complete prevention. Ethanol induced a drastic decrease of reduced glutathione liver content as well as 630 and 133% increases of blood and liver acetaldehyde contents, respectively. S-Adenosyl-L-methionine treatment almost completely reconstituted the liver reduced glutathione pool and caused a large decrease of the liver and blood acetaldehyde contents. 1-Chloro-2,4-dinitrobenzene, which depletes the cellular reduced glutathione, and diethylethanolamine, an inhibitor of the phosphatidylethanolamine methylation, abolished the S-adenosyl-L-methionine-induced modifications of the reduced glutathione, acetaldehyde, and triacylglycerol contents in the liver of ethanol-treated rats. Neither S-adenosyl-L-methionine nor reduced glutathione inhibitors affected the liver acetaldehyde dehydrogenase activity. It is suggested that, although S-adenosyl-L-methionine induced a small inhibition of ethanol metabolism in the liver, its antisteatosic effect could largely depend on its role as a modulator of the reduced glutathione liver content.
研究了S-腺苷-L-甲硫氨酸对慢性乙醇摄入诱导的大鼠肝脏脂肪变性的保护作用。在乙醇处理期间给予S-腺苷-L-甲硫氨酸可预防脂肪变性，在乙醇戒断后给予则可加速从脂肪变性中恢复。它还对急性和慢性中毒大鼠的血液乙醇消耗有轻微抑制作用。由于S-腺苷-L-甲硫氨酸处理，急性乙醇中毒大鼠以及正常大鼠中约30%的乙醇脱氢酶受到抑制，但微粒体乙醇氧化系统未受抑制。比较S-腺苷-L-甲硫氨酸和吡唑对乙醇氧化和脂肪积累的抑制作用，发现吡唑对乙醇代谢的更大抑制与脂肪变性的不完全预防相关，而S-腺苷-L-甲硫氨酸的较低抑制与完全预防相关。乙醇导致肝脏中还原型谷胱甘肽含量急剧下降，血液和肝脏中乙醛含量分别增加630%和133%。S-腺苷-L-甲硫氨酸处理几乎完全恢复了肝脏还原型谷胱甘肽池，并使肝脏和血液中乙醛含量大幅下降。耗尽细胞内还原型谷胱甘肽的1-氯-2,4-二硝基苯和磷脂酰乙醇胺甲基化抑制剂二乙氨基乙醇消除了S-腺苷-L-甲硫氨酸诱导的乙醇处理大鼠肝脏中还原型谷胱甘肽、乙醛和三酰甘油含量的变化。S-腺苷-L-甲硫氨酸和还原型谷胱甘肽抑制剂均未影响肝脏乙醛脱氢酶活性。提示，尽管S-腺苷-L-甲硫氨酸对肝脏乙醇代谢有轻微抑制作用，但其抗脂肪变性作用可能很大程度上取决于其作为肝脏还原型谷胱甘肽含量调节剂的作用。
