Hultberg Malin, Hultberg Björn
Institute of Laboratory Medicine, Department of Clinical Chemistry, University Hospital, S-22185 Lund, Sweden.
Chem Biol Interact. 2006 Nov 7;163(3):192-8. doi: 10.1016/j.cbi.2006.08.001. Epub 2006 Aug 12.
Glutathione plays crucial roles in antioxidant defence and glutathione deficiency contributes to oxidative stress and may therefore play a key role in the pathogenesis of many diseases. The objectives of the present study were to evaluate the effects on glutathione turnover of thiol and non-thiol antioxidants in human cell cultures and if any of the antioxidant had a short-term cellular effect against different levels of hydrogen peroxide.
We have investigated the effect on the total glutathione amount in HeLa and hepatoma cell cultures of thiol antioxidants in comparison with non-thiol antioxidants, such as a copper chelator, Vitamin C, and a flavonoid. Furthermore, we have investigated the short-term (within 24h) interaction of the different antioxidants with hydrogen peroxide.
Lipoic acid and quercetin (Quer) were the two antioxidants that showed the highest stimulation of glutathione synthesis in cell cultures as judged by the total glutathione amount. However, no antioxidant protected against hydrogen peroxide present in concentrations that lowered cell protein. This finding may be attributed to the fact that it is necessary to incubate cell cultures with antioxidants or small doses of oxidants for a period before the cultures are exposed to hydrogen peroxide in order to enhance the antioxidant defence. The presence of Quer and Vitamin C lowered cell protein and total glutathione even in cell cultures containing hydrogen peroxide in concentrations that did not lower cell protein. This finding might be attributed to pro-oxidant properties and formation of excess reactive oxygen species in the presence of Quer and Vitamin C.
谷胱甘肽在抗氧化防御中起关键作用,谷胱甘肽缺乏会导致氧化应激,因此可能在许多疾病的发病机制中起关键作用。本研究的目的是评估巯基和非巯基抗氧化剂对人细胞培养物中谷胱甘肽周转的影响,以及是否有任何抗氧化剂对不同水平的过氧化氢具有短期细胞效应。
我们研究了巯基抗氧化剂与非巯基抗氧化剂(如铜螯合剂、维生素C和类黄酮)相比,对HeLa细胞和肝癌细胞培养物中总谷胱甘肽含量的影响。此外,我们还研究了不同抗氧化剂与过氧化氢的短期(24小时内)相互作用。
根据总谷胱甘肽含量判断,硫辛酸和槲皮素是在细胞培养物中显示出对谷胱甘肽合成刺激作用最强的两种抗氧化剂。然而,没有抗氧化剂能抵御降低细胞蛋白质的过氧化氢浓度。这一发现可能归因于这样一个事实,即在细胞培养物暴露于过氧化氢之前,有必要先用抗氧化剂或小剂量氧化剂孵育一段时间,以增强抗氧化防御。即使在含有不会降低细胞蛋白质的过氧化氢浓度的细胞培养物中,槲皮素和维生素C的存在也会降低细胞蛋白质和总谷胱甘肽。这一发现可能归因于槲皮素和维生素C存在时的促氧化特性和过量活性氧的形成。