Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, 11439, USA.
Adv Exp Med Biol. 2017;975 Pt 1:353-369. doi: 10.1007/978-94-024-1079-2_31.
This study has compared the effects of metformin (MET) and taurine (TAU), singly and in combination, on the oxidative stress caused by diabetes in the rat brain. For this purpose, male Sprague-Dawley rats, 200-225 g in weight, assigned to groups of 6, were intraperitoneally (i.p.) treated with the diabetogen streptozotocin (STZ, 60 mg/kg, in citrate buffer pH 4.5) on day 1 and, after 14 days, orally (p.o.) with either MET, TAU or MET-TAU (each at 2.4 mM/kg, in water). Control rats received only citrate buffer pH 4.5 (2 mL) or only STZ on day 1 by the i.p. route. All the animals were sacrificed by decapitation on day 57 and their brains collected by the freeze clamp technique. Blood samples were placed in heparinized tubes and used for the assay of the plasma glucose (GLC) and blood insulin (INS) levels. Immediately thereafter, the brains were surgically removed and a portion was used to prepare a homogenate in 0.1 M PBS pH 7.4, which was used for the assay of indices of oxidative stress. Diabetes raised the plasma GLC level (+313%) but lowered that of the blood INS (-76%) compared to corresponding values from nondiabetic rats. In addition it raised the brain malondialdehyde level (+59%) but lowered the reduced/disulfide glutathione ratio (-46%), and activities of catalase (-43%), glutathione peroxidase (-48%), superoxide dismutase (-65%), glutathione reductase (-50%) and glutathione S-transferase (-51%) significantly (all at p < 0.001). Except for the greater decrease in GLC (+90% vs. +22%) and increase in INS (-26% vs. -52%) levels seen in rats receiving MET than in rats receiving TAU, these compounds protected the brain against oxidative stress to significant (p ≤ 0.05%) and rather similar extents. Furthermore, the concurrent administration of MET and TAU to the diabetic rats led to brain values of indices of oxidative stress that were lower than those attained with MET alone, although generally not to a statistically significant degree.
这项研究比较了二甲双胍（MET）和牛磺酸（TAU）单独及联合应用对糖尿病大鼠大脑氧化应激的影响。为此，雄性 Sprague-Dawley 大鼠，体重 200-225g，分为 6 组，于第 1 天经腹腔（i.p.）给予链脲佐菌素（STZ，60mg/kg，在柠檬酸缓冲液 pH4.5 中），14 天后，经口（p.o.）给予 MET、TAU 或 MET-TAU（均为 2.4mM/kg，在水中）。对照组大鼠仅给予柠檬酸缓冲液 pH4.5（2mL）或仅在第 1 天经 i.p.途径给予 STZ。所有动物于第 57 天断头处死，采集大脑。血液样本置于肝素化管中，用于测定血浆葡萄糖（GLC）和血液胰岛素（INS）水平。立即切除大脑，部分用于制备 0.1M PBS pH7.4 匀浆，用于测定氧化应激指标。与非糖尿病大鼠相比，糖尿病使血浆 GLC 水平升高（+313%），但血液 INS 水平降低（-76%）。此外，它使脑丙二醛水平升高（+59%），但使还原/二硫谷胱甘肽比降低（-46%），并使过氧化氢酶（-43%）、谷胱甘肽过氧化物酶（-48%）、超氧化物歧化酶（-65%）、谷胱甘肽还原酶（-50%）和谷胱甘肽 S-转移酶（-51%）活性显著降低（均为 p<0.001）。除了 MET 组大鼠的 GLC 下降幅度较大（+90%对+22%）和 INS 增加幅度较小（-26%对-52%）外，这些化合物都显著（p≤0.05%）且程度相当的保护了大脑免受氧化应激的影响。此外，将 MET 和 TAU 同时给予糖尿病大鼠，使大脑氧化应激指标值低于单独使用 MET 时的水平，但通常没有达到统计学意义。
