De La Cruz J P, Pavía J, González-Correa J A, Ortiz P, Sánchez de la Cuesta F
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain.
Naunyn Schmiedebergs Arch Pharmacol. 2000 Jan;361(1):47-52. doi: 10.1007/s002109900153.
S-adenosyl-L-methionine (SAM), used to treat liver diseases and as a coadjuvant in antidepressive medication, has neuroprotective effects in animal models. The aim of this study was to discover whether SAM has antioxidant effects in rat brain tissue. Ten male Wistar rats were killed by decapitation and the forebrains incubated with SAM for in vitro experiments. To study the effects of long-term administration, animals in four groups of ten rats each were given 10 mg SAM/kg per day s.c., and 40 other rats were given an equivalent volume of L-lysine (the commercial solvent for SAM). Treatment was started at the end of lactation, and animals were killed by decapitation after 15 days or 1, 6 or 22 months of treatment. The forebrain of each animal was used to test membrane lipid peroxidation by determining thiobarbituric acid-reactive substances (TBARS), glutathione level and enzyme activities related to glutathione (reduced form GSH, oxidized form GSSG) metabolism: GSH-peroxidase (GSHpx), GSSD-reductase (GSSGrd) and GSH-transferase (GSHtf). Chronic treatment with SAM decreased maximum forebrain production of TBARS by 46% compared with animals given L-lysine and increased glutathione levels by 50%, GSHpx activity by 115% and GSHtf activity by 81.4%. The results of in vitro experiments were qualitatively similar: lipid peroxidation was inhibited (13.1+/-1.3 nmol/mg protein in controls vs. 5.9+/-0.8 nmol/mg protein in samples incubated with 1000 micromol/l SAM) and glutathione levels were stimulated (0.97+/-0.06 micromol/g tissue in control samples vs. 1.55+/-0.08 micromol/g tissue in samples incubated with 1000 micromol/l SAM), as were GSHpx and GSHtf. No significant effect was seen in any of the experiments with L-lysine. We conclude that SAM has antioxidant effects in rat brain tissue both in vitro and ex vivo. The effect is seen both as inhibition of lipid peroxide production and as an enhancement of the endogenous glutathione antioxidant system.
S-腺苷-L-甲硫氨酸（SAM）用于治疗肝脏疾病，并作为抗抑郁药物的辅助剂，在动物模型中具有神经保护作用。本研究的目的是探究SAM在大鼠脑组织中是否具有抗氧化作用。10只雄性Wistar大鼠断头处死，取其前脑用于体外实验，并与SAM一起孵育。为研究长期给药的效果，将4组每组10只大鼠每日皮下注射10 mg SAM/kg，另外40只大鼠注射等量的L-赖氨酸（SAM的商业溶剂）。治疗从哺乳期结束时开始，在治疗15天、1个月、6个月或22个月后断头处死动物。取每只动物的前脑，通过测定硫代巴比妥酸反应性物质（TBARS）、谷胱甘肽水平以及与谷胱甘肽（还原型GSH、氧化型GSSG）代谢相关的酶活性：谷胱甘肽过氧化物酶（GSHpx）、谷胱甘肽二硫化物还原酶（GSSGrd）和谷胱甘肽转移酶（GSHtf），来检测膜脂质过氧化。与注射L-赖氨酸的动物相比，SAM长期治疗使前脑TBARS的最大产量降低了46%，谷胱甘肽水平提高了50%，GSHpx活性提高了115%，GSHtf活性提高了81.4%。体外实验结果在性质上相似：脂质过氧化受到抑制（对照组为13.1±1.3 nmol/mg蛋白质，与1000 μmol/l SAM孵育的样品为5.9±0.8 nmol/mg蛋白质），谷胱甘肽水平受到刺激（对照样品为0.97±0.06 μmol/g组织，与1000 μmol/l SAM孵育的样品为1.55±0.08 μmol/g组织），GSHpx和GSHtf也是如此。在任何使用L-赖氨酸的实验中均未观察到显著效果。我们得出结论，SAM在体外和体内对大鼠脑组织均具有抗氧化作用。这种作用表现为抑制脂质过氧化物的产生以及增强内源性谷胱甘肽抗氧化系统。
