A comparison between effects of pyruvate and herb medicines in preventing experimental oxalate urolithiasis in rats

Sodium pyruvate, choreito (a herbal preparation), and urajirogashi (a herb) were added to a calcium-oxalate lithogenic diet (a glycolic-acid diet) to determine their effects in preventing lithogenicity. Male Wistar-strain rats which had been fed the glycolic-acid diet developed marked urinary calculi within 4 weeks. Rats in the groups fed a pyruvate diet had, however, almost no stones in the urinary system. The choreito and urajirogashi were slightly less effective than the pyruvate. Urinary oxalate excretion was high in all the groups during the experiment, especially in the pyruvate and the glycolic-acid groups, but, it was relatively lowered in the herb groups, especially towards the end of the experiment (p less than 0.05). Urinary citrate excretion was high in the pyruvate group, but it was significantly low in the other groups. In the choreito group, remarkable increases in urinary volume and magnesium excretion were observed; however, they were statistically non-significant and urinary calcium excretion was higher than in the glycolic-acid group during the experiment. Therefore, it can be concluded that choreito and urajirogashi may have some beneficial effect though any such effect is inferior to that of pyruvate, in preventing calculi formation, partly by decreasing the urinary oxalate excretion; increased urine volume and magnesium excretion may also have some other, additional effects in the choreito group.     

Effects of sodium citrate, potassium citrate, and citric acid in preventing experimental calcium oxalate urolithiasis in rats

Male Wistar-strain rats which had been fed a glycolic-acid diet developed severe nephrocalcinosis with urinary calculi within 4 weeks. Rats fed the same diet with citrate salts added had, however, either slight or no nephrocalcinosis without any stones in the urinary system. Nephrocalcinosis intermediate between those in the citrate groups and the glycolic-acid group, with some urinary calculi, was observed in the citric-acid group. During the experiment, the urinary oxalate concentration increased markedly and was higher in the citrate and citric-acid than in the glycolic-acid group. The urinary citrate concentration was significantly higher in the citrate groups and lower in the citric acid and glycolic-acid groups. Therefore, citrate salts can be concluded to inhibit nephrocalcinosis and calculi formation as a result of decreased urinary saturation by means of increase in urinary citrate, in spite of a slight increase in the urinary oxalate.     

Comparative study of the effects of pyruvate and CG-120 in preventing experimental oxalate urolithiasis in rats

Male Wistar-strain rats which had been fed a calcium-oxalate lithogenic diet (a glycolate diet) developed urinary calculi in 4 weeks. Sodium pyruvate or CG-120 (a mixture of citrate salts) had been added to this diet to determine its effect in preventing lithogenicity. Rats in the group fed a pyruvate diet had, however, almost no stones in the urinary system. Rats in the CG-120 group showed results somewhat similar to those in the pyruvate group. Increased urinary citrate excretion was observed in both groups and could be implicated as the main inhibitory factor in stone formation. Therefore, it can be concluded that CG-120 exerts a beneficial effect close to that of pyruvate in preventing calculi formation and that both substances cause a high citrate excretion in urine.     

Glycosaminoglycans,uric acid and calcium oxalate urolithiasis

Summary The interaction between calcium and glycosaminoglycans (GAGs) was studied using a calcium ion-selective electrode. The Ca-binding capacity of GAGs involved 16% of total calcium in the presence of chondroitin sulphate and 28% in the presence of pentosan polysulphate. The action of GAGs on the nucleation of uric acid and sodium urate was examined and inhibitory effects were observed. The action of uric acid as a heterogeneous nucleant of calcium oxalate was studied, and considerable promotion of the heterogeneous nucleation of calcium oxalate by uric acid was found, which could be inhibited by the action of GAGs. From these summarised in vitro results, we conclude that uric can constitute an important risk factor for calcium oxalate urolithiasis through heterogeneous nucleation and the GAGs can play an important role as preventive agents.     

Pathogenesis of oxalate urolithiasis: lessons from experimental studies with rats

Calcium oxalate (CaOx) urolithiasis in rats is induced by producing hyperoxaluria. Depending on the degree and length of hyperoxaluria, CaOx crystals may either form in the nephron or the bladder and may or may not be retained in the kidneys. Crystals may nucleate in one part of the nephron and be retained in another part. Papillary collecting duct tubular epithelium and its basement membrane appear to be involved in crystal retention in the kidneys.     

Effects of low-molecular-weight polyguluronate sulfate on experimental urolithiasis in rats

Urinary macromolecules, especially glycosaminoglycans (GAGs), have attracted great interest as promising inhibitors of urinary stone formation. As an analogue of GAGs, low-molecular-weight polyguluronate sulfate (LPGS) with strong polyanionic nature was prepared by chemical modification of brown algae extract. The effects of LPGS both on ethylene glycol-induced nephrolithiasis and Zinc disc implant-induced urinary bladder stone formation in Wistar rats were evaluated, and its acute toxicity in Kunming mice and Wistar rats were also investigated. The contents of renal oxalate and calcium in ethylene glycol-induced nephrolithiasic rats were decreased significantly from 5.01 ± 0.96 to 3.26 ± 1.31 μmol/g kidney (P < 0.01) and 20.11 ± 4.60 to 11.83 ± 3.54 μmol/g kidney (P < 0.01), respectively, after oral administration of LPGS at dose-level of 100 mg/kg. The renal crystal depositions and histopathological changes were reduced also. The formation of zinc disc implant-induced urinary bladder stones in rats was inhibited considerably after oral administration of LPGS at dose-levels of 50 mg/kg (P < 0.05) and 100 mg/kg (P < 0.01). The intravenous LD₅₀ and the oral maximum tolerance value of LPGS in mice are 6.29 and 25 g/kg, and in rats are 2.25 and 10 g/kg, respectively. These data show that LPGS has significant prevention effects both on nephrolithiasis and urinary bladder stone formation in rats, and negligible oral toxicity both in mice and rats. LPGS is a safe and promising drug candidate for the prevention of urolithiasis.     

α-亚麻酸对草酸钙结石鼠前列腺素E2的影响

目的：探讨前列腺素E2在尿结石形成中的作用以及α-亚麻酸对前列腺素E2的抑制作用。方法：将60只雄性Wistar成年大鼠随机分成空白对照组、成石组、苏子油组、葵花籽油组。所有大鼠适应性喂养1周后，空白对照组随后7周均饮用自来水。成石组前4周饮用自来水，后3周饮用诱石剂水，每日自来水2g／只灌胃1次。苏子油组7周内每日以苏子油2g／只灌胃1次，饮水同成石组。葵花油组7周内每日以葵花油2g／只灌胃1次，饮水同B组。8周后检测大鼠24h尿总钙、尿总镁、尿草酸、肌酐和各组大鼠尿前列腺素E2水平。结果：空白对照组和苏子油组尿总钙明显低于成石组。尿总镁、尿草酸对照组明显低于成石组，苏子油组、葵花籽油组、成石组之间则差异无显著性意义。尿肌酐对照组、苏子油组、葵花油组显著低于成石组。24h尿前腺素E2水平苏子油组、对照组显著低于成石组。葵花籽油组与成石组比较差异无显著性意义。成石组、苏子油组、葵花籽油组前列腺素E2水平与尿总钙含量成正相关性。结论：前列腺素E2可能参与并促进了尿结石的形成，α-亚麻酸可能通过抑制肾前列腺素E2的产生而抑制尿结石形成。     

碘海醇对实验性大鼠草酸钙结石形成的影响

目的探讨造影剂碘海醇对大鼠草酸钙结石形成的影响。方法将40只Wister大鼠随机分为成4组：空白对照组（A）、单纯诱石组（B）、单纯碘海醇组（C）、诱石＋碘海醇组（D）。用乙二醇法诱导建立大鼠草酸钙结石模型,C、D组尾静脉注射碘海醇。实验第4周末检测肾组织中丙二醛（MDA）含量及超氧化物歧化酶（SOD）活力,镜下观察肾内草酸钙晶体沉积情况。结果A、B、C、D4组肾脏组织MDA含量（nmol／mg蛋白）分别为2．74±0．48、4．51±1．47、6．92±2．18、8．87±2．31,SOD活力（U／mg蛋白）分别195．21±11．01、170．24±13．59、140．86±25．91、121．54±25．50,各组间差异有统计学意义（P〈0．05）。B、D组结晶等级评分高于A组,D组结晶等级评分高于B组（P〈1．05）。培论碘海醇促进了大鼠肾小管内草酸结晶量的增加,其机制与碘海醇诱导的肾小管上皮氧化应激损伤有关。     

Epidemiology,pathogenesis and diagnosis of calcium oxalate urolithiasis

In the German Federal Republic, the incidence of urolithiasis is 0.54% and the prevalence is 4%. Calcium oxalate stones are to be expected in over 60% of the cases. Pathogenetic factors are discussed. It is demonstrated that the overconsumption of chocolate, rhubarb and spinach brings about risk situations for stone formation, while asparagus and tomatoes present no risk. The increased animal protein and alcohol intake may be the most important reasons for the accumulations of calcium oxalate stones. Beside the minimum investigation programme it is demon trated by examples that recurrent stone formers need an extended investigation to find out more about the pathogenesis, in order to determine an effective treatment or to prevent recurrences.Dedicated to Prof. Dr. Med. Sc. A. Babics, Budapest, on the occasion of his 80th birthday.     

Urinary oxalic acid excretion differs after oral loading of rats with various oxalate salts

BACKGROUND: To compare urinary oxalate excretion after the oral administration of oxalic acid, disodium oxalate, or calcium oxalate in rats. METHODS: Male Wistar rats were divided into four groups of six rats each and were intravenously hydrated with normal saline, and then were administered normal saline (control group), 10 mg of oxalic acid, equimolar disodium oxalate, or equimolar calcium oxalate via a gastrostomy. Urine specimens were collected just before administration and at hourly intervals up to 5 h afterwards. The urinary oxalate, calcium, magnesium and phosphorus levels were measured. RESULTS: Urinary oxalate excretion peaked at 1-2 h after administration of oxalic acid or equimolar disodium oxalate, while administration of calcium oxalate only caused a small increase of urinary oxalate excretion. Cumulative urinary oxalate excretion during 5 h was 1.69 +/- 0.10 mg (mean +/- SD; 17%), 1.43 +/- 0.13 mg (13%), and 0.22 +/- 0.03 mg (2%) after the administration of oxalic acid, disodium oxalate, and calcium oxalate, respectively. Urinary calcium excretion showed a decrease in the oxalic acid and disodium oxalate groups, while urinary magnesium or phosphorus excretion did not change significantly. CONCLUSION: The upper gastrointestinal tract seems to be the major site of oxalic acid absorption and only free oxalate is absorbed irrespective of whether it is the sodium salt or not. After binding to calcium in the gut, oxalic acid absorption seems to be inhibited in the presence of calcium and this means that calcium oxalate is poorly absorbed (at least in the upper gastrointestinal tract).     

维生素D_3和维生素K_3对实验性肾结石的影响

目的　探讨维生素D3 和维生素K3 与尿石症的关系。　方法　SD大鼠 36只 ,随机分为对照组 (A组 )、成石组 (B组 )、维生素D3 组 (C组 )、成石 维生素D3 组 (D组 )、维生素K3 组 (E组 )和成石 维生素K3 组 (F组 ) ,用免疫组化和原位杂交技术检测各组大鼠肾脏骨桥蛋白 (OPN)及其mRNA的表达量 ,并测定尿晶体成分的浓度。　结果　免疫组化结果显示 ,OPN主要表达于肾脏远曲小管和集合管 ,B、C、E组鼠肾OPN的表达强度明显高于A组 (P均 <0 .0 5 ) ;D、F组OPN的表达强度明显高于C、E组 (P均 <0 .0 5 ) ,即维生素D3 或维生素K3 与诱石剂合用时呈相加效应。应用诱石剂后 ,D组尿钙排泄量明显增加 ,而F组草酸盐明显低于B组 (P <0 .0 5 )。维生素K3 可减少尿草酸盐的分泌和草酸钙晶体的沉积。　结论　维生素D3 可能通过多种机制促进肾结石形成 ,而维生素K3 有抑制结石形成的作用。     

维生素D3和维生素K3对实验性肾结石的影响

目的：探讨维生素C3和维生素K3与尿石症的关系。方法SD大鼠36只,随机分为对照组（A组）、成石组（B组）、维生D3组（C组）、成石＋维生素D3组（D组）、维生素K3组（E组）和成石＋维生素K3组（F组）,用免疫组化和原位杂交技术检测各组大鼠肾脏骨桥蛋白（OPN）及其mRNA的表达量,并测定尿晶体成分的浓度。结果：免疫组化结果显示,OPN主要表达于肾脏远曲小管和集合管,B、C、E组鼠肾和OPN的表达强度明显高于A组（P均＜0．05）;D、F组OPN的表达强度明显高于C、E组（P均＜0．05）,即维生素D3或维生素K3与诱石剂合用时呈相加效应。应用诱石剂后,D组尿钙排泄量明显增加,而F组草酸盐明显低于B组（P＜0．05）。维生素K3可减少尿划石剂后,D组尿排泄量明显增加,而组草酸盐明显低于B组（P＜0．05）。维生素K3可减少尿草酸盐的分泌和草酸钙晶体的沉积。结论：维生素D3可能通过多种机制种促进肾结石殂成,而维生素K3有抑制结石形成的作用。     

Effect of Costus igneus stem extract on calcium oxalate urolithiasis in albino rats

The effects of aqueous and ethanolic extracts of Costus igneus (stem) and isolated compounds lupeol and stigmasterol on calcium oxalate urolithiasis have been studied in male albino Wistar rats. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and oxalate. The increased deposition of stone-forming constituents in the urine, serum, and kidney homogenate of urolithic rats was significantly (p?<?0.05) lowered by treatment using aqueous and ethanolic extracts of C. igneus (stem), and isolated compounds lupeol and stigmasterol. The calcium oxalate crystal deposition in the kidney was significantly greater in ethylene glycol-induced urolithic rats. After administration of aqueous and ethanolic extract of C. igneus, the deposition of calcium and oxalate was significantly lowered. Treatment with lupeol and stigmasterol significantly reduced the deposition of calcium and oxalate in the kidney, and also in the blood serum; the lipid profile serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels at 50 and 100?mg/kg were significantly (p?<?0.05) lowered in urolithiatic rats. From this study, we conclude that both the treatments with aqueous and ethanolic extract of C. igneus (stem) and isolated compounds lupeol and stigmasterol had an inhibitory effect on calcium oxalate urinary stone. Lupeol and stigmasterol were identified from the stem of C. igneus by high-performance thin layer chromatography technique. The isolated compounds were confirmed by Fourier transform infrared (FTIR) and ¹³C NMR spectra.     

Acute hyperoxaluria, renal injury and calcium oxalate urolithiasis.

Single intraperitoneal injections of three, seven, or 10 mg. of sodium oxalate per 100 gm. of rat body weight were administered to male Sprague-Dawley rats. At various times after the injection, urine samples were analyzed for oxalate, and urinary enzymes, alkaline phosphatase, leucine aminopeptidase, gamma-glutamyl transpeptidase, and N-acetyl-beta-glucosaminidase. The kidneys were processed for light microscopy and renal calcium and oxalate determination. Oxalate administration resulted in an increase in urinary oxalate and formation of calcium oxalate crystals in the kidneys. The amount and duration of urinary excretion of excess oxalate and retention of crystals in the kidneys correlated with the dose of sodium oxalate administered. At a low oxalate dose of three mg./100 gm., crystals moved rapidly down the nephron and cleared the kidneys. At higher doses crystals were retained in kidneys and at a dose of 10 mg./100 gm. were still there seven days post-injection. Crystal retention was associated with enhanced excretion of urinary enzymes indicating renal tubular epithelial injury.     

The role of magnesium in calcium oxalate urolithiasis

The aim of this study was to evaluate the effect of magnesium on calcium oxalate crystal formation, both in physiological conditions and at slightly higher oxalate concentrations, using a mixed suspension mixed product removal crystallizer and scanning electron microscopy. True supersaturation ratios were calculated by allowing for complexation in solution. Magnesium inhibited the nucleation rate at all oxalate concentrations. It also inhibited the growth rate at oxalate concentrations of less than approximately 2.0 mmol/l but promoted the growth rate at higher concentrations. This suggests that, provided the oxalate concentration is sufficiently high, increase of magnesium concentration can increase the crystal growth rate. At physiological concentrations of oxalate, however, magnesium decreases both nucleation and growth rates. The SEM photographs showed that the predominant crystal was calcium oxalate trihydrate at low magnesium concentrations, with calcium oxalate dihydrate being observed in larger quantities at high magnesium concentrations.     

特发性草酸钙结石的病因和治疗

大概有10%的人一生中会罹患泌尿系结石症,而这当中有大约80%为草酸钙结石,临床上大多数草酸钙结石无明显遗传背景和相关系统性疾病,称为特发性草酸钙结石[1-2].此类结石第一次发病经过治疗后5年复发率约为45%,20年的复发率约为75%,对人类的健康造成极大损害.因此,充分认识其病因对预防、治疗和降低其复发率尤其重要.