title: In vitro anti-lithogenic activity of lime powder regimen (LPR) and the effect of LPR on urinary risk factors for kidney stone formation in healthy volunteers.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Pajaree
authors.initials: P
authors.lastname: Chariyavilaskul
authors.forename: Poonsin
authors.initials: P
authors.lastname: Poungpairoj
authors.forename: Suchada
authors.initials: S
authors.lastname: Chaisawadi
authors.forename: Chanchai
authors.initials: C
authors.lastname: Boonla
authors.forename: Thasinas
authors.initials: T
authors.lastname: Dissayabutra
authors.forename: Phisit
authors.initials: P
authors.lastname: Prapunwattana
authors.forename: Piyaratana
authors.initials: P
authors.lastname: Tosukhowong
mesh_terms: D000328:Adult; D000818:Animals; D017610:Calcium Compounds / Q000627:therapeutic use*; D002478:Cells, Cultured; D018592:Cross-Over Studies; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007669:Kidney Calculi / Q000517:prevention & control; D008297:Male; D051379:Mice; D053040:Nephrolithiasis / Q000517:prevention & control*; D010087:Oxides / Q000627:therapeutic use*; D011208:Powders; D012307:Risk Factors
chemical_list: D017610:Calcium Compounds; D010087:Oxides; D011208:Powders; C016538:lime