Chariyavilaskul Pajaree, Poungpairoj Poonsin, Chaisawadi Suchada, Boonla Chanchai, Dissayabutra Thasinas, Prapunwattana Phisit, Tosukhowong Piyaratana
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Urolithiasis. 2015 Apr;43(2):125-34. doi: 10.1007/s00240-015-0751-y. Epub 2015 Jan 15.
Hypocitraturia, hypokaliuria, and increased oxidative stress are common lithogenic risk factors found in nephrolithiasis patients, especially in Thailand. We previously developed lime powder regimen (LPR), and demonstrated that LPR delivered citraturic, alkalinizing, and antioxidative effects in kidney stone patients. In this study, in vitro anti-lithogenic activity, in vivo acute toxicity, and crossover-designed phase 1 trial (in 13 healthy volunteers) of LPR were investigated. LPR inhibited the growth of calcium oxalate monohydrate (COM) crystals in dose-dependent manner, and inhibited the intracellular production of reactive oxygen species (ROS) in COM-treated HK-2 cells. LPR did not significantly alter viability of HK-2 cells. No acute toxicity was detected in mice orally fed with LPR (10 g/kg). No adverse effect and complaint of LPR ingestion (5 g/dose) were observed in the tested volunteers. Plasma citrate was elevated at 30 min after LPR load, which was higher than the water load control. Plasma potassium was significantly elevated at 30 min after LPR load and remained high for 2 h, and at 2 h, it was significantly higher than the water load. Urinary citrate was significantly increased at 1 h after LPR load and remained high for 2 h, and at 2 h, it was significantly higher than the water load. Urinary potassium was significantly increased at 1 h after LPR load and remained high for 3 h, and its levels at 1, 2, and 3 h were significantly higher than the water load. Urinary total antioxidant status was significantly increased at 2 h after LPR load. In conclusion, LPR had an inhibitory effect on COM growth and exerted as antioxidant to attenuate ROS production in the COM-treated renal tubular cells. LPR provided citraturic, kaliuric, and antioxidative responses in healthy individuals without any adverse events. This suggests that LPR is well tolerated and safe for daily consumption.
低枸橼酸尿症、低钾尿症和氧化应激增加是肾结石患者常见的致石危险因素，在泰国尤其如此。我们之前开发了石灰粉方案（LPR），并证明LPR对肾结石患者具有增加枸橼酸排泄、碱化尿液和抗氧化作用。在本研究中，我们对LPR进行了体外抗结石活性、体内急性毒性研究以及交叉设计的1期试验（13名健康志愿者参与）。LPR以剂量依赖性方式抑制一水合草酸钙（COM）晶体的生长，并抑制COM处理的HK-2细胞内活性氧（ROS）的产生。LPR对HK-2细胞的活力没有显著影响。口服LPR（10 g/kg）的小鼠未检测到急性毒性。在受试志愿者中未观察到LPR摄入（5 g/剂量）的不良反应和主诉。LPR负荷后30分钟血浆枸橼酸盐升高，高于水负荷对照组。LPR负荷后30分钟血浆钾显著升高，并在2小时内保持高位，且在2小时时显著高于水负荷组。LPR负荷后1小时尿枸橼酸盐显著增加，并在2小时内保持高位，且在2小时时显著高于水负荷组。LPR负荷后1小时尿钾显著增加，并在3小时内保持高位，其在1、2和3小时的水平显著高于水负荷组。LPR负荷后2小时尿总抗氧化状态显著增加。总之，LPR对COM生长具有抑制作用，并作为抗氧化剂减弱COM处理的肾小管细胞中ROS的产生。LPR在健康个体中引起了增加枸橼酸排泄、排钾和抗氧化反应，且无任何不良事件。这表明LPR耐受性良好，日常食用安全。
