Pragasam Viswanathan, Kalaiselvi Periandavan, Sumitra Kamalanathan, Srinivasan Shunmugarajan, Varalakshmi Palaninathan
Department of Medical Biochemistry, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai-600 113, India.
Clin Chim Acta. 2005 Apr;354(1-2):159-66. doi: 10.1016/j.cccn.2004.11.029. Epub 2005 Jan 19.
Our understanding of nitrosative stress in the process of urolithiasis is far from complete. Earlier studies carried out in our laboratory demonstrate the presence of nitrated THP in stone formers, l-arginine (l-arg) a precursor of nitric oxide (NO), attenuates the endothelial dysfunction caused by reactive nitrogen species. We investigated the role of l-arg in ethylene glycol (EG)-induced urolithic rat model and observed its antilithic and antioxidative properties.
Hyperoxaluria was induced using 0.75% EG in drinking water. l-arg [1.25 g/kg body weight] was given orally for a period of 28 days.
EG-treated rats showed significant loss in body weight and increase in the activities of oxalate synthesizing enzymes such as glycollic acid oxidase in liver. Lactate dehydrogenase activity in liver and kidney was increased. The activity of the free radical producing enzyme xanthine oxidase, tissue oxalate and calcium levels were significantly increased in EG-treated rats. Depletion in the antioxidant enzymes, membrane bound ATPases and thiol status was observed in these rats. l-arg co-supplementation to EG-treated rats maintained the activities of the oxalate synthesizing enzymes and free radical producing enzymes with in the normal range. Tissue oxalate and calcium levels were also maintained near normal in l-arg treated hyperoxaluric rats. l-arg, by its cytoprotective effect, maintained the thiol status, thereby preserving the activities of the membrane bound ATPases and preventing proteinuria and subsequent weight loss in EG-treated rats.
l-arg feeding prevents the retention of calcium oxalate crystals in hyperoxaluric rats by way of protecting the renal cells from oxidative injury and also by providing a second line of defense through the normalization of the oxalate metabolism. It reduces the risk of stone formation, by curtailing free radicals and hyperoxaluria as both of them have to work in close association to form stones.
我们对尿石症过程中氧化亚氮应激的理解还远远不够全面。我们实验室早期开展的研究表明，结石患者体内存在硝基化的THP，一氧化氮（NO）的前体L-精氨酸（L-arg）可减轻活性氮物质引起的内皮功能障碍。我们研究了L-arg在乙二醇（EG）诱导的尿石症大鼠模型中的作用，并观察了其抗结石和抗氧化特性。
通过在饮用水中添加0.75%的EG诱导高草酸尿症。口服给予L-arg[1.25 g/kg体重]，持续28天。
EG处理的大鼠体重显著减轻，肝脏中草酸合成酶如乙醇酸氧化酶的活性增加。肝脏和肾脏中的乳酸脱氢酶活性升高。EG处理的大鼠中，产生自由基的酶黄嘌呤氧化酶的活性、组织草酸和钙水平显著升高。这些大鼠的抗氧化酶、膜结合ATP酶和巯基状态出现耗竭。对EG处理的大鼠补充L-arg可使草酸合成酶和产生自由基的酶的活性维持在正常范围内。L-arg处理的高草酸尿症大鼠的组织草酸和钙水平也维持在接近正常的水平。L-arg通过其细胞保护作用维持巯基状态，从而保持膜结合ATP酶的活性，并防止EG处理的大鼠出现蛋白尿和随后的体重减轻。
L-arg喂养可防止高草酸尿症大鼠体内草酸钙晶体的潴留，其方式是保护肾细胞免受氧化损伤，并通过使草酸代谢正常化提供第二道防线。它通过减少自由基和高草酸尿症降低结石形成的风险，因为这两者必须密切协同作用才能形成结石。
