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牛磺酸对内毒素血症大脑 8-羟基脱氧鸟苷和 3-硝基酪氨酸水平的影响。

Effect of taurine on brain 8-hydroxydeoxyguanosine and 3-nitrotyrosine levels in endotoxemia.

机构信息

Tubitak, Ankara, Turkey.

出版信息

Inflammation. 2012 Apr;35(2):665-70. doi: 10.1007/s10753-011-9359-8.

Abstract

Taurine is a sulfur-containing β-amino acid that is found in milimolar concentrations in most mammalian tissues and plasma. It was shown to have cytoprotective effects in many in vitro and in vivo studies and these actions are often attributed to an antioxidant mechanism. In this study, we aimed to investigate the effect of acute taurine administration on endotoxin-induced oxidative and nitrosative stress in brain. Fourty adult male guinea pigs were divided into four groups: control, taurine, endotoxemia, and endotoxemia + taurine. Taurine (300 mg/kg), lipopolysaccharide (LPS, 4 mg/kg), or taurine plus LPS was administered intraperitoneally. After 6 h of incubation, when highest blood levels of taurine and endotoxin were attained, the animals were killed and brain tissue samples were collected. 3-Nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHdG) and taurine levels were measured using high-performance liquid chromatography methods. LPS administration significantly increased 3-NT, 8-OHdG levels, and dramatically reduced taurine concentrations in brain tissue compared to control group. The groups in which taurine was administered alone or with LPS, contradiction to well-known antioxidant effect, taurine caused elevated concentrations of 3-NT and 8-OHdG compared to both control and endotoxemia groups. In conclusion, endotoxemia leads to tyrosine nitration and DNA base modification that can be assessed by 3-NT and 8-OHdG, respectively. Taurine did not exhibit any antioxidant effect; moreover, it may contribute to neuronal damage at this dose. Thus, we can suggest that lower dose of taurine administration may be benefial for neuronal protection or adversely taurine administration may have toxic effect at all doses.

摘要

牛磺酸是一种含硫的β-氨基酸,在大多数哺乳动物组织和血浆中以毫摩尔浓度存在。它在许多体外和体内研究中显示出细胞保护作用,这些作用通常归因于抗氧化机制。在这项研究中,我们旨在研究急性牛磺酸给药对内毒素诱导的大脑氧化和硝化应激的影响。40 只成年雄性豚鼠分为四组:对照组、牛磺酸组、内毒素血症组和内毒素血症+牛磺酸组。牛磺酸(300mg/kg)、脂多糖(LPS,4mg/kg)或牛磺酸加 LPS 经腹腔注射给药。孵育 6 小时后,当达到牛磺酸和内毒素的最高血药浓度时,处死动物并采集脑组织样本。使用高效液相色谱法测定 3-硝基酪氨酸(3-NT)、8-羟基脱氧鸟苷(8-OHdG)和牛磺酸水平。与对照组相比,LPS 给药显著增加了 3-NT、8-OHdG 水平,并显著降低了脑组织中的牛磺酸浓度。与对照组和内毒素血症组相比,单独给予牛磺酸或与 LPS 给予牛磺酸的组,与众所周知的抗氧化作用相反,导致 3-NT 和 8-OHdG 浓度升高。总之,内毒素血症导致酪氨酸硝化和 DNA 碱基修饰,分别可以通过 3-NT 和 8-OHdG 来评估。牛磺酸没有表现出任何抗氧化作用;此外,它可能在该剂量下导致神经元损伤。因此,我们可以建议,较低剂量的牛磺酸给药可能对内​​科神经元保护有益,或者相反,牛磺酸给药可能在所有剂量下都具有毒性作用。

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