Singh Abhishek Kumar, Singh Sandeep, Garg Geetika, Rizvi Syed Ibrahim
Department of Biochemistry, University of Allahabad, Allahabad-211002, India.
Biochem Cell Biol. 2016 Oct;94(5):471-479. doi: 10.1139/bcb-2016-0048. Epub 2016 Jun 6.
An imbalanced cellular redox system promotes the production of reactive oxygen species (ROS) that may lead to oxidative stress-mediated cell death. Erythrocytes are the best-studied model of antioxidant defense mechanism. The present study was undertaken to investigate the effect of the immunosuppressant drug rapamycin, an inducer of autophagy, on redox balance of erythrocytes and blood plasma of oxidatively challenged rats. Male Wistar rats were oxidatively challenged with HgCl (5 mg/kg body mass (b.m.)). A significant (p < 0.05) induction in ROS production, plasma membrane redox system (PMRS), intracellular Ca influx, lipid peroxidation (LPO), osmotic fragility, plasma protein carbonyl (PCO) content, and plasma advanced oxidation protein products (AOPP) and simultaneously significant reduction in glutathione (GSH) level and ferric reducing ability of plasma (FRAP) were observed in rats exposed to HgCl. Furthermore, rapamycin (0.5 mg/kg b.m.) provided significant protection against HgCl-induced alterations in rat erythrocytes and plasma by reducing ROS production, PMRS activity, intracellular Ca influx, LPO, osmotic fragility, PCO content, and AOPP and also restored the level of antioxidant GSH and FRAP. Our observations provide evidence that rapamycin improves redox status and attenuates oxidative stress in oxidatively challenged rats. Our data also demonstrate that rapamycin is a comparatively safe immunosuppressant drug.
细胞氧化还原系统失衡会促进活性氧（ROS）的产生，这可能导致氧化应激介导的细胞死亡。红细胞是对抗氧化防御机制研究得最为透彻的模型。本研究旨在探讨免疫抑制药物雷帕霉素（一种自噬诱导剂）对遭受氧化应激的大鼠红细胞和血浆氧化还原平衡的影响。雄性Wistar大鼠经HgCl₂（5 mg/kg体重）进行氧化应激处理。在暴露于HgCl₂的大鼠中，观察到ROS生成、质膜氧化还原系统（PMRS）、细胞内Ca²⁺内流、脂质过氧化（LPO）、渗透脆性、血浆蛋白羰基（PCO）含量以及血浆晚期氧化蛋白产物（AOPP）显著（p < 0.05）诱导，同时谷胱甘肽（GSH）水平和血浆铁还原能力（FRAP）显著降低。此外，雷帕霉素（0.5 mg/kg体重）通过减少ROS生成、PMRS活性、细胞内Ca²⁺内流、LPO、渗透脆性、PCO含量和AOPP，为HgCl₂诱导的大鼠红细胞和血浆改变提供了显著保护，还恢复了抗氧化剂GSH水平和FRAP。我们的观察结果证明雷帕霉素可改善遭受氧化应激大鼠的氧化还原状态并减轻氧化应激。我们的数据还表明雷帕霉素是一种相对安全的免疫抑制药物。
