Muthukumar A, Selvam R
Department of Microbiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi.
Mol Cell Biochem. 1998 Aug;185(1-2):77-84. doi: 10.1023/a:1006817319876.
Role of glutathione on kidney mitochondrial integrity and function during stone forming process in hyperoxaluric state was investigated in male albino rats of Wistar strain. Hyperoxaluria was induced by feeding ethylene glycol (EG) in drinking water. Glutathione was depleted by administering buthionine sulfoximine (BSO), a specific inhibitor of glutathione biosynthesis. Glutathione monoester (GME) was administered for supplementing glutathione. BSO treatment alone or along with EG, depleted mitochondrial GSH by 40% and 51% respectively. Concomitantly, there was remarkable elevation in lipid peroxidation and oxidation of protein thiols. Mitochondrial oxalate binding was enhanced by 74% and 129% in BSO and BSO + EG treatment. Comparatively, EG treatment produced only a 33% increase in mitochondrial oxalate binding. Significant alteration in calcium homeostasis was seen following BSO and BSO + EG treatment. This may be due to altered mitochondrial integrity and function as evidenced from decreased activities of mitochondrial inner membrane marker enzymes, succinate dehydrogenase and cytochrome-c-oxidase and respiratory control ratio and enhanced NADH oxidation by mitochondria in these two groups. NADH oxidation (r = -0.74) and oxalate deposition in the kidney (r = -0.70) correlated negatively with mitochondrial glutathione depletion. GME supplementation restored normal level of GSH and maintained mitochondrial integrity and function, as a result of which oxalate deposition was prevented despite hyperoxaluria. These results suggest that mitochondrial dysfunction resulting from GSH depletion could be a contributing factor in the development of calcium oxalate stones.
在Wistar品系的雄性白化大鼠中，研究了谷胱甘肽在高草酸尿状态下结石形成过程中对肾脏线粒体完整性和功能的作用。通过在饮用水中添加乙二醇（EG）诱导高草酸尿。通过给予丁硫氨酸亚砜胺（BSO，一种谷胱甘肽生物合成的特异性抑制剂）来消耗谷胱甘肽。给予谷胱甘肽单酯（GME）来补充谷胱甘肽。单独使用BSO或与EG联合使用，分别使线粒体谷胱甘肽（GSH）减少40%和51%。同时，脂质过氧化和蛋白质硫醇氧化显著升高。在BSO和BSO + EG处理组中，线粒体草酸结合分别增强了74%和129%。相比之下，EG处理仅使线粒体草酸结合增加了33%。在BSO和BSO + EG处理后，观察到钙稳态有显著改变。这可能是由于线粒体完整性和功能改变所致，这两组中线粒体内膜标记酶琥珀酸脱氢酶和细胞色素c氧化酶的活性降低、呼吸控制率降低以及线粒体对NADH氧化增强均证明了这一点。NADH氧化（r = -0.74）和肾脏中草酸盐沉积（r = -0.70）与线粒体谷胱甘肽消耗呈负相关。补充GME可恢复GSH的正常水平并维持线粒体的完整性和功能，结果是尽管存在高草酸尿，但草酸盐沉积得以预防。这些结果表明，谷胱甘肽消耗导致的线粒体功能障碍可能是草酸钙结石形成的一个促成因素。
