Rajasekaran Namakkal Surappan, Devaraj Niranjali S, Devaraj Halagowder
Unit of Biochemistry, Department of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India.
Biochim Biophys Acta. 2004 Mar 2;1688(2):121-9. doi: 10.1016/j.bbadis.2003.11.004.
The protective effects of glutathione monoester (GME) on buthionine sulfoximine (BSO)-induced glutathione (GSH) depletion and its sequel were evaluated in rat erythrocyte/erythrocyte membrane. Animals were divided into three groups (n=6 in each): control, BSO and BSO+GME group. Administration of BSO, at a concentration of 4 mmol/kg bw, to the albino rats resulted in depletion of blood GSH level to about 59%. GSH was elevated several folds in the GME group as compared to the control (P<0.05) and BSO (P<0.001) groups. Decreased concentration of vitamin E was found in the erythrocyte membrane isolated from BSO-administered animals. Antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were also found to be altered due to BSO-induced GSH depletion in blood erythrocytes. The SOD and CAT activities in BSO group were significantly lower (P<0.001) than the other groups. Lipid peroxidation index and malondialdehyde (MDA) levels in erythrocytes and their membranes were increased to about 45% and 40%, respectively. The activities of Ca2+ ATPase, Mg2+ ATPase and Na+K+ ATPase were lower than those of control group (P<0.05), whereas the activities of these enzymes were found to be restored to normal followed by GME therapy (P<0.05). Cholesterol, phospholipid and C/P ratio and some of the phospholipid classes like phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin were significantly (P<0.05) altered in the erythrocyte membranes of BSO-administered rats compared with those of control group. These parameters were restored to control group levels in GME-treated group. Oxidative stress may play a major role in the BSO-mediated gamma glutamyl cysteine synthetase (gamma-GCS) inhibition and hence the depletion of GSH. In conclusion, our findings have shown that antioxidant status decreased and lipid peroxidation increased in BSO-treated rats. GME potentiates the RBC and blood antioxidant defense mechanisms and decreases lipid peroxidation.
在大鼠红细胞/红细胞膜中评估了谷胱甘肽单酯（GME）对丁硫氨酸亚砜胺（BSO）诱导的谷胱甘肽（GSH）耗竭及其后续影响。动物分为三组（每组n = 6）：对照组、BSO组和BSO + GME组。以4 mmol/kg体重的浓度给白化大鼠施用BSO，导致血液GSH水平耗竭至约59%。与对照组（P < 0.05）和BSO组（P < 0.001）相比，GME组的GSH升高了几倍。在从施用BSO的动物分离的红细胞膜中发现维生素E浓度降低。还发现抗氧化酶过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）由于BSO诱导的血液红细胞中GSH耗竭而发生改变。BSO组的SOD和CAT活性显著低于其他组（P < 0.001）。红细胞及其膜中的脂质过氧化指数和丙二醛（MDA）水平分别增加至约45%和40%。Ca2 + ATP酶、Mg2 + ATP酶和Na + K + ATP酶的活性低于对照组（P < 0.05），而在GME治疗后发现这些酶的活性恢复正常（P < 0.05）。与对照组相比，施用BSO的大鼠红细胞膜中的胆固醇、磷脂和C/P比值以及一些磷脂类如磷脂酰胆碱（PC）、溶血磷脂酰胆碱（LPC）和鞘磷脂显著（P < 0.05）改变。在GME治疗组中，这些参数恢复到对照组水平。氧化应激可能在BSO介导的γ-谷氨酰半胱氨酸合成酶（γ-GCS）抑制以及因此导致的GSH耗竭中起主要作用。总之，我们的研究结果表明，BSO处理的大鼠抗氧化状态降低，脂质过氧化增加。GME增强了红细胞和血液的抗氧化防御机制并减少了脂质过氧化。
