Nencini C, Giorgi G, Micheli L
Department of Pharmacology Giorgio Segre, University of Siena, Italy.
Phytomedicine. 2007 Feb;14(2-3):129-35. doi: 10.1016/j.phymed.2006.02.005. Epub 2006 Apr 25.
Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. Previously, we have pointed out a dramatic decrease of glutathione levels in the rat brain after acetaminophen (APAP) oral administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study, we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats were treated with SM (200 mg/kg/die orally) for three days, or with APAP single oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and APAP single oral administration (3 g/kg) at third day. Successively the following parameters were measured: reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD) and malondialdehyde levels (MDA). Our results showed a significant decrease of GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels after APAP administration. After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH values significantly increase and the others parameters remained unchanged respect to control values. These results suggest that SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels.
大脑易受氧化应激影响，且与年龄相关的脑功能障碍有关。此前，我们指出对乙酰氨基酚（APAP）口服过量后大鼠脑中谷胱甘肽水平急剧下降。水飞蓟素（SM）是从水飞蓟中分离出的生物活性黄酮木脂素的混合物，通常用于治疗酒精性肝病，并作为人类的抗肝毒性药物。在本研究中，我们评估了SM对APAP诱导损伤后大鼠脑内酶促和非酶促抗氧化防御系统的影响。雄性白化Wistar大鼠连续三天口服SM（200mg/kg/天），或单次口服APAP（3g/kg），或连续三天口服SM（200mg/kg/天）并在第三天单次口服APAP（3g/kg）。随后测量以下参数：还原型和氧化型谷胱甘肽（GSH和GSSG）、抗坏血酸（AA）、超氧化物歧化酶（SOD）的酶活性变化以及丙二醛水平（MDA）。我们的结果显示，APAP给药后GSH水平、AA水平和SOD活性显著降低，MDA和GSSG水平升高。给予SM后，GSH和AA显著增加，SOD活性显著增强。在SM + APAP组中，GSH值显著增加，其他参数相对于对照值保持不变。这些结果表明，SM可能因其预防脂质过氧化和补充GSH水平的能力而保护中枢神经系统免受氧化损伤。
