Kheir-Eldin A A, Motawi T K, Gad M Z, Abd-ElGawad H M
Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., 11562, Cairo, Egypt.
Int J Biochem Cell Biol. 2001 May;33(5):475-82. doi: 10.1016/s1357-2725(01)00032-2.
The major goal of this study was to examine the ability of several antioxidants namely, vitamin E, beta-carotene and N-acetylcysteine, to protect the brain from oxidative stress induced by lipopolysaccharide (LPS, endotoxin). LPS, a component of the bacterial wall of gram-negative bacteria, has been recognized as one of the most potent bacterial products in the induction of host inflammatory responses and tissue injury and was used in this study to mimic infections. LPS injection resulted in a significant increase in the stress indices, plasma corticosterone and glucose concentration, a significant alteration of the brain oxidative status observed as elevation of the level of malondialdehyde (MDA, index of lipid peroxidation) and reduction of reduced glutathione (GSH), and a disturbance in the brain energy metabolism presented as a reduction in the ATP/ADP ratio and an increase in the mitochondrial/cytosolic hexokinase ratio. However, the activities of brain superoxide dismutase and Na+, K+-ATPase and contents of cholesterol and phospholipids were not altered. Administration of the aforementioned antioxidants prior to LPS injection ameliorated the oxidative stress by reducing levels of MDA, restoring GSH content and normalizing the mitochondrial/cytosolic hexokinase ratio in the brain in addition to lowering levels of plasma corticosterone and glucose. In conclusion, this study showed the increased free radical generation during infections and LPS-induced stress. It also suggests that brain oxidative status and energy is disturbed.
本研究的主要目的是检测几种抗氧化剂，即维生素E、β-胡萝卜素和N-乙酰半胱氨酸，保护大脑免受脂多糖（LPS，内毒素）诱导的氧化应激的能力。LPS是革兰氏阴性菌细胞壁的一种成分，已被认为是诱导宿主炎症反应和组织损伤的最有效的细菌产物之一，本研究中用其模拟感染。注射LPS导致应激指标、血浆皮质酮和葡萄糖浓度显著升高，大脑氧化状态发生显著改变，表现为丙二醛（MDA，脂质过氧化指标）水平升高和还原型谷胱甘肽（GSH）减少，大脑能量代谢紊乱，表现为ATP/ADP比值降低和线粒体/胞质己糖激酶比值升高。然而，大脑超氧化物歧化酶和Na+、K+-ATP酶的活性以及胆固醇和磷脂的含量没有改变。在注射LPS之前给予上述抗氧化剂，除了降低血浆皮质酮和葡萄糖水平外，还通过降低MDA水平、恢复GSH含量和使大脑线粒体/胞质己糖激酶比值正常化来减轻氧化应激。总之，本研究表明感染和LPS诱导的应激期间自由基生成增加。研究还表明大脑氧化状态和能量受到干扰。
