Cymbopogon proximus and Petroselinum crispum seed ethanolic extract/Gum Arabic nanogel emulsion: Preventing ethylene glycol and ammonium chloride-induced urolithiasis in rats.

Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters' excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations.

Felbamate urolithiasis.

Drug-induced nephrolithiasis is an important consideration in recurrent stone formers with polypharmacy. While felbamate nephrolithiasis has previously been published in the paediatric population, we present the oldest published case of a felbamate stone in an adult, a man in his 30s with Lennox-Gastaut syndrome. Even with moderate dosing, high drug serum levels can occur. Performing at least one stone analysis remains a critical component to care in these patients. Urologists should have a high index of suspicion for drug stone when stone analysis returns indeterminate characterisation in the absence of infection. Close communication with neurology is key to preventing recurrent stone disease.

Nephroprotective effect of PHYMIN-22 on ethylene glycol induced urolithiasis rat model.

The present study was designed to evaluate the antiurolithiatic effect of PHYMIN-22 against ethylene glycol-induced urolithiasis in rats. Healthy Albino male rats with 200-230 g body weight were randomly divided into five groups, each with 5 animals, control group, EG group (0.75%), PHYMIN-22 treatment group (0.75% EG 14 days and 100 mg/kg PHYMIN-22 next 14 days), PHYMIN-22 drug control group (100 mg/kg) and cystone treatment group (0.75% EG 14 days and 750 mg/kg cystone next 14 days). Biochemical testing was adopted for measuring the blood and urine parameters, as well as the level of antioxidants including superoxide dismutase (SOD), Catalase (Cat), Glutathione peroxidase (GPx) and glutathione (GSH) in kidney tissues. Hematoxylin and eosin (HE) staining was utilized to observe the histopathological changes in the kidney tissue. End of the experiment the PHYMIN-22 treatment reduced the urine and serum calcium (p < 0.01; p < 0.01), oxalate (p < 0.01; p < 0.01), phosphate (p < 0.01; p < 0.01), uric acid (p < 0.001; p < 0.001), protein (p < 0.001; p < 0.001), and creatinine (p < 0.001; p < 0.001) respectively, serum indicators ALT (p < 0.001) and AST (p < 0.001) level and non-enzymic antioxidant GSH (p < 0.001) compared to EG induced urolithiasis animals (Diseased control group). PHYMIN-22 treatment significantly increased urine volume, pH, and body weight, and antioxidants include CAT (p < 0.001; p < 0.001), SOD (p ˃ 0.05; p < 0.05), and GPX (p < 0.01; p < 0.001) compared to Diseased control group animals. The effect of PHYMIN-22 on EG-induced urolithiasis animals could be by improving kidney function, normalizing the urine and serum parameters, maintaining the kidney antioxidants, eliminating crystal deposition, and excretion of unwanted ions from the kidney and urinary tract.

Exacerbation of Renal, Cardiovascular, and Respiratory Outcomes Associated with Changes in Climate.

Exposure to environmental variables including declining air quality and increasing temperatures can exert detrimental effects on human health including acute exacerbations of chronic diseases. We aim to investigate the association between these exposures and acute health outcomes in a rural community in Colorado. Meteorological and adult emergency department visit data were retrospectively collected (2013-2017); for asthma outcomes, additional data were available (2003-2017). Daily environmental exposure data included PM10, maximum daily temperature (MDT), and mean humidity and precipitation. Total daily counts of emergency department (ED) diagnoses for myocardial infarction, congestive heart failure, urolithiasis, and exacerbation of chronic obstructive pulmonary disease (COPD) and asthma, were calculated during the study period. Time series models using generalized estimating equations were fit for each disease and included all four environmental factors. Between 2013 and 2017, asthma and COPD exacerbation accounted for 30.8% and 25.4% of all ED visits (n=5,113), respectively. We found that for every 5˚C increase in MDT, the rate of urolithiasis visits increased by 13% (95% CI: 2%, 26%) and for every 10µg/m3 increase in 3-day moving average PM10, the rate of urolithiasis visits increased by 7% (95% CI: 1%, 13%). The magnitude of association between 3-day moving average PM10 and rate of urolithiasis visits increased with increasing MDT. The rate of asthma exacerbation significantly increased as 3-day, 7-day, and 21-day moving average PM10 increased. This retrospective study on ED visits is one of the first to investigate the impact of several environmental exposures on adverse health outcomes in a rural community. Research into mitigating the negative impacts of these environmental exposures on health outcomes is needed.

Association of short-term nitrogen dioxide exposure with hospitalization for urolithiasis in Xinxiang, China: a time series study.

Urolithiasis accounts for the highest incidence of all urologic-associated hospitalizations. However, few studies have explored the effect of nitrogen dioxide (NO2) on hospitalizations for urolithiasis. We included 5956 patients with urolithiasis, collected daily meteorological and air pollution data between 2016 and 2021, and analyzed the associations between air pollutants and hospitalization, length of the hospital stay, and hospitalization costs attributable to urolithiasis. NO2 exposure was associated with an increased risk of hospitalization for urinary tract stones. For each 10-µg/m3 increase and 1-day lag of NO2, the maximum daily effect on the risk of hospitalization for urolithiasis was 1.020 (95% confidence interval [CI]: 1.001-1.039), and the cumulative effect peaked on lag day 4 (relative risk [RR]: 1.061; 95% CI: 1.003-1.122). Attribution scores and quantitative analysis revealed that the mean number of hospital days and mean hospital costs were 16 days and 21,164.39 RMB, respectively. Up to 5.75% of all urolithiasis hospitalizations were estimated to be attributable to NO2, and the cost of NO2-related urolithiasis hospitalizations reached approximately 3,430,000 RMB. Stratified analysis showed that NO2 had a more sensitive impact on urolithiasis hospitalizations in women and in those aged ≥65 years. Notably, men and those younger than 65 years of age (exclude people aged 65) incurred more costs for urolithiasis hospitalizations. In the population level, the association between NO2 and risk of urolithiasis hospitalization was more pronounced during the warm season. NO2 can increase hospitalizations for urolithiasis for Xinxiang City residents, and there is a cumulative lag effect. Focusing on air pollution may have practical significance in terms of the prevention and control of urolithiasis.

In vivo investigation of the inhibitory effect of Peganum harmala L. and its major alkaloids on ethylene glycol-induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.

Anti-urolithiatic Activity of Daidzin in Ethylene Glycol-Induced Urolithiasis in Rats.

Urolithiasis is a common urological disorder, which causes considerable morbidity in both genders at all age groups worldwide. Though treatment options such as diuretics and non-invasive techniques to disintegrate the deposits are available, but often they are found less effective in the clinics. In this work, we planned to investigate the ameliorative effects of daidzin against the ethylene glycol (EG)-induced urolithiasis in rats. The male albino rats were distributed into four groups (n = 6) as control (group I), urolithiasis induced by the administration of 0.75% EG (group II), urolithiasis induced rats treated with 50 mg/kg of daidzin (group III), and urolithiasis rats treated with standard drug 750 mg/kg of cystone (group IV). The urine volume, pH, and total protein in the urine were assessed. The activities of marker enzymes in both plasma and kidney tissues were analyzed using assay kits. The levels of kidney function markers such as calcium, oxalate, urea, creatinine, uric acid, magnesium, BUN, and phosphorous were estimated using assay kits. The status of antioxidants and inflammatory cytokines were also examined using kits. The renal tissues were examined by histopathological analysis. Our results revealed that the daidzin treatment effectively decreased the urine pH and protein level and increased the urine volume in the urolithiasis rats. Daidzin decreased the calcium, oxalate, uric acid, and urea, creatinine, and BUN levels and also improved the magnesium and phosphorus in the urolithiasis rats. The activities of AST, ALT, ALP, GGT, and LDH were effectively reduced by the daidzin in both serum and renal tissue. Daidzin also reduced the inflammatory marker and increased the antioxidant levels. Histopathology results also proved the therapeutic effects of daidzin. Together, our results displayed that daidzin is effective in the amelioration of EG-induced urolithiasis in rats.

Discerning Comparison of 1 and 0.5% Ethylene Glycol in Sprague-Dawley Rats with Modeled Urolithiasis.

A common method of modeling urolithiasis is the use of 1 and 0.75% ethylene glycol, or a combination of ethylene glycol with other lithogens, but too rapid progression of the disease and multiple organ toxicity have been reported. We developed a urolithiasis model in Sprague-Dawley rats, in which the animals received a relatively low concentration of ethylene glycol (0.5%), but for a long-term period (6 weeks) followed by animal observation during the 6-week recovery period. In urine samples, signs of the urolithiasis development were observed starting from the sixth week: the presence of ketones, decrease in diuresis and urine pH; in the blood, urea, protein, and hematocrit were elevated. However, no leukocytes were detected in the urine; in the blood, no shifts in differential leukocyte count and no elevation in ALT, creatinine, cholesterol, and triglycerides were observed, which indicates the absence of multiple organ failure while using 1% ethylene glycol. In addition, the animals receiving 0.5% ethylene glycol were followed up to 12 weeks in contrast to animals receiving 1% ethylene glycol (the experiment in this case was stopped during the third week for ethical reasons).

Consumption of soft drinks rich in phosphoric acid versus struvite crystallization from artificial urine.

In recent years, there has been a continuous increase in the incidence of urolithiasis, especially in highly developed countries. Therefore, the question arises which factors specific to these countries may be responsible for the increase in the incidence of this disease. In this article, we try to assess the effect of phosphoric acid, a component of various carbonated drinks, including Coca-Cola, on the nucleation and growth of struvite crystals, which are the main component of infectious urinary stones. The research was carried out in the environment of artificial urine with and without the presence of Proteus mirabilis bacteria. In the latter case, the activity of bacterial urease was simulated by adding an aqueous ammonia solution. The obtained results indicate that phosphoric acid present in artificial urine causes the nucleation of struvite to shift towards a lower pH, which means that struvite nucleates earlier in artificial urine compared to the control test. The amount of struvite formed is the greater the higher the concentration of phosphoric acid. At the same time, as the concentration of phosphoric acid increases, the growing struvite crystals are larger, which is disadvantageous because they are more difficult to remove from the urinary tract along with the urine. For the highest levels of phosphoric acid tested, large dendrites are formed, which are particularly undesirable as they can damage the epithelium of the urinary tract. The effect of phosphoric acid on the nucleation and growth of struvite is explained in base of chemical speciation analysis. This analysis indicates that the MgHCit and MgCit- complexes have the main influence on the nucleation and growth of struvite in artificial urine in the presence of phosphoric acid. It should be keep in mind that all these effects of phosphoric acid are possible when the urinary tract is infected with urease-positive bacteria. In the absence of infection, phosphoric acid will not cause struvite to crystallize.

Pyrrosia petiolosa Extract Ameliorates Ethylene Glycol-Induced Urolithiasis in Rats by Inhibiting Oxidative Stress and Inflammatory Response.

Objective: To study the therapeutic effect and mechanism of Pyrrosia petiolosa (P. petiolosa) extract on ethylene glycol- (EG-) induced urolithiasis in rats. Methods: Thirty SD male rats were randomly divided into five groups (n = 6): control group, EG group, and P. petiolosa group (25 mg/kg, 50 mg/kg group, and 100 mg/kg). Biochemical testing was adopted for measuring the blood and urine parameters, as well as the level of superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde acid (MDA) in kidney tissues. HE staining and ELISA were utilized to observe the histopathological changes and detect the level of IL-1ß, IL-6, MCP-1, and TNF-α in the kidney tissue, respectively. And western blot was performed for checking NOX2, NOX4, TGF-ß1, p-Smad3, Smad3, p-Smad2, and Smad2 protein expression level in kidney tissues. Results: EG could significantly increase the level of blood urea nitrogen, creatinine, and Na in serum and 24-hour urinary protein, oxalate, uric acid, creatinine, calcium, and phosphorus in urine and decreased the urine volume in rats. Whereas P. petiolosa extract was able to greatly decrease the level of related parameters in serum and urine in a dose-dependent manner, but did not affect the urine pH. In addition, P. petiolosa extract notably ameliorated EG-induced renal tissue injury. Compared with the EG group, P. petiolosa extract markedly raised the level of SOD and GSH and decreased the MDA level and the expression of NOX2 and NOX4 in the kidney tissue. Moreover, P. petiolosa extract also lowered the level of IL-1ß, IL-6, MCP-1, and TNF-α in EG-stimulated kidney tissue and inhibited the protein level of EG-induced TGF-ß1, p-Smad3, and p-Smad2 in a concentration-dependent manner. Conclusion: P. petiolosa extract can improve EG-induced urolithiasis in rats by inhibiting oxidative stress, inflammatory response, and the activation of TGF-ß pathway.

Effect of methanolic extract of Mimosa malacophylla A.Gray in vero and HEK-293 cell lines, and in the morphology of kidney and bladder of rats with induced urolithiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithiasis is the presence of stones in the kidney, ureters, bladder and/or urethra; it is the third most frequent disease of the urinary tract. Mimosa malacophylla A. Gray, is a species distributed in northern Mexico, where people traditionally use it for its diuretic effect, and to treat kidney diseases; however, no scientific reports have been found in relation to its antiurolithic properties. AIM OF THE STUDY: This study aimed to obtain a qualitative phytochemical profile of the methanolic extract (ME) of M. malacophylla, and to evaluate its potential cytotoxic effect in vitro and its antiurolithic activity in vivo. MATERIAL AND METHODS: Phytochemical screening was performed to demonstrate the presence of secondary metabolite groups in the methanolic extract of M. malacophylla. In vitro cytotoxicity assays (MTT and nucleotide labeling with DAPI) were performed to evaluate the effect of the extract on kidney cell lines. Urolithiasis was induced in the bladder of Wistar rats introducing zinc disks for the calculus formation and exposed to three concentrations of ME. RESULTS: Phytochemical screening showed phenols, steroids, terpenoids and carbohydrates. In vitro analysis demonstrated that concentrations below 300 µg/mL of ME did not produce a cytotoxic effect on renal Vero and HEK-293 cells. In vivo analysis of 15 days of exposition, revealed that the extract at concentrations of 50 mg/kg to 150 mg/kg were effective as an antiurolithic treatment, and did not produce morphological alterations in kidney or bladder in murine model of induced urolithiasis. CONCLUSIONS: The antiurolithic activity may be attributed to the presence of flavonoids, steroids and terpenes detected in the phytochemical screening which have been reported to possess this activity. These results could be useful to evaluate new alternatives and their potential therapeutic effect to treat renal or urinary affections.

Urinary Excretion of Cyanuric Acid in Association with Urolithiasis: A Matched Case-Control Study in Shanghai Adults.

Melamine (MEL) has raised human concern since the 2008 milk scandal. Co-exposure to MEL and one of its analogues, cyanuric acid (CYA), has been reported to have a synergistic effect on promoting urolithiasis. However, few epidemiological studies have reported urolithiasis in association with exposure to CYA based on our knowledge. We therefore conducted a case-control study to investigate whether cases of urolithiasis had higher excretion of urinary CYA than the controls. Spot urine samples from 70 adult cases and first-morning urine samples from 70 controls (matched by age and sex) were collected for the measurement of MEL, CYA, and other two analogues in urine. The case group also had 2.81-fold higher concentration of urinary CYA than the control group (34.87 versus 12.43 ng/mL, p-value < 0.001). Multivariate conditional logistic regression models adjusting potential confounders of personal characteristics identified the risk factor of urinary CYA as a continuous variable with odds ratio (OR) (95% confidence interval, 95%CI) of 1.11 (1.02−1.21) (p-value = 0.021) and having meals at restaurants with OR of 5.71 (1.01−32.31) (p-value = 0.049). Compared to the participants having the lowest quartile of CYA concentration in urine, participants at the second, third, and fourth quartile groups had ORs of 13.94, 83.69, and 118.65 with p-values of 0.004, <0.001, and <0.001, respectively. The high excretion of urinary CYA in urolithiasis cases might be the sign of stones in patients consisting of CYA, then proving the attribution of CYA exposure in the etiology of urolithiasis. These findings are important since CYA is a degraded by-product of chlorinated isocyanuric acid disinfectants, which are widely used in daily life not only in swimming pool water but also in other scenarios, such as serving as anti-pandemic disinfectants. Risk assessment of CYA serving as a by-product of disinfectants needs to be conducted in future studies.

Long-term safety of eldecalcitol in Japanese patients with osteoporosis: a retrospective, large-scale database study.

INTRODUCTION: This real-world study evaluated whether long-term use of eldecalcitol (ELD) increases the risk of adverse events (AEs), namely, hypercalcemia, acute kidney injury (AKI), and urolithiasis, and analyzed the ELD-induced risk of rare AEs such as osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF). MATERIALS AND METHODS: Patient records were retrieved from Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. The ELD-treated osteoporosis patient cohort (ELD cohort) was analyzed to determine the incidence rate of the aforementioned AEs. The patient cohort that was prescribed active vitamin D3 other than ELD (AVD cohort) was analyzed as the reference. RESULTS: Incidence rates of hypercalcemia, AKI, and urolithiasis in the ELD cohort were 0.942, 0.517, 2.465 events per 100 person-years, respectively, in the MDV dataset, and 0.687, 0.155, 3.785, respectively, in the JMDC dataset. The incidence rates of these AEs in the ELD cohort remained relatively constant throughout ELD treatment. A small number of patients experienced ONJ or AFF during ELD or AVD treatment. The number of ONJ and AFF cases in the both cohorts decreased over time. The two cohorts showed no difference in the concomitant use of anti-bone resorptive agents such as bisphosphonates and denosumab. CONCLUSION: The risk of hypercalcemia and AKI associated with ELD use observed in this retrospective analysis is similar to that reported previously in the Japanese post-marketing surveillance of ELD. Furthermore, ELD, similar to AVD, may not increase the risk of ONJ and AFF.

Biochemical and molecular effects of a commercial diuretic with herbal extract on experimentally induced urolithiasis in chickens.

This study evaluated the diuretic, antioxidant, anti-inflammatory, and immunological effects of a commercial diuretic (CD) (composed of ammonium chloride, potassium citrate, sodium chloride, ascorbic acid, biotin, halfa bar extract, and hexamine) on chickens with induced urolithiasis. A total of 100 one-day-old white Hy-Line chicks were fed a basal diet containing 20% crude protein (CP) and 1% Ca until they reached 48 days of age. Then, the birds were divided into five groups (G1-G5). G1 was fed a basal diet and kept as a negative control, G2 was fed a high protein (HP) diet containing 25% crude protein, G3 was fed high calcium (HC) diet containing 5% Ca, G4 was fed HP diet supplemented with CD, and G5 was fed HC diet supplemented with CD. The CD was supplemented with drinking water (at a dose of 0.5 ml/ liter) for 1 week. The experiment was held for 78 days. Clinical signs, postmortem lesions, and mortality rates were observed. Biochemical analytes, redox status biomarkers, and expression of interleukin-6 (IL-6) and interferon-gamma (IFN-γ) were measured. Tissue samples were taken for histopathological examination. No signs of CD toxicity were observed during the toxicity test prior to the experiment. Compared to all groups, birds in G2 and G3 showed impaired renal function and alterations in biochemical, redox status, lipid peroxidation, post-mortem, and histopathological lesions along with upregulation of IL-6 and IFN-γ in the kidney and spleen. In conclusion, commercial diuretic supplementation for one week improves renal function, redox status, immune and anti-inflammatory responses in chickens with induced urolithiasis.

Anti urolithiatic activity of Cyperus rotundus tubers: In silico, In vitro and In vivo approaches

Abstract The present research evaluated the anti urolithic potential of Cyperus rotundus tubers extract using in silico, in vitro and in vivo techniques. In silicostudy was performed of Cyperus rotundus constituents and pathological protein oxalate oxidase (PDB Id: 2ETE). In vitrostudy, nucleation and aggregation assay involved for assessment of ethanol extract of Cyperus rotundus tuber (50-3000 µg/ml).In vivo studies involved that the Cyperus rotundusethanolic extract (100, 200 and 400 mg/kg B.wt.) wastreatedonsodium oxalate induced urolithiatic rats for seven days,evaluated kidney function by urine and serum biochemical analysis and statistical analysis performed usingGraphPad prism5 software.In silico results showedthat Cyperus rotundus constituents,Humulene epoxide, 4-Oxo-alpha-ylangene, Cubebol were exhibited better binding energyonoxalate oxidase.Ethanolic extract of Cyperus rotundustuber was exhibited nucleation, aggregation of calcium oxalate monohydrate crystals inhibition in dosedependent manner. Sodium oxalate treatment was triggered biochemical changesin the urine that have been substantially prevented by the ethanolic extract of Cyperus rotundus tuber. The current findings Cyperus rotundus anti urolithic activity due to antioxidant essential oils. The molecular docking results could be used to optimize lead and develop the appropriate urolithiasis treatment.

Prophylactic and curative potential of peppermint oil against calcium oxalate kidney stones.

Mentha piperita L., a well-known traditional herb, constitutes essential oil as one of its important constituent, used for its flavor, aroma and therapeutic applications. Based on the antioxidant, antispasmodic and nephroprotective potential, the essential oil of Mentha piperita was evaluated for its preventive and curative effects against ethylene glycol induced urolithiasis. Peppermint oil (Mp.Eo) was evaluated for its antioxidant potential by DPPH method. Urolithiasis was developed in male rats by the administration of ammonium chloride and ethylene glycol in drinking water. Different doses of Mp.Eo (10, 30 and 50 mg/kg) and cystone, the standard antiurolithic drug (500 mg/kg), were given along with stone-inducing regimen in prophylactic model and after intoxication for the next fourteen days in curative model. Urine and serum were analyzed for various biochemical parameters. One representative kidney from each group was studied for changes in histological parameters. Mp.Eo was found to be effective against urolithiasis-associated changes including crystalluria, polyuria and acidic urine. Mp.Eo also neutralized the altered levels of urinary uric acid, magnesium, total protein, serum creatinine and serum BUN. The data obtained from the present study demonstrated the therapeutic importance of peppermint oil against urolithiasis.

Nephroprotective effect of Bryophyllum pinnatum-mediated silver nanoparticles in ethylene glycol-induced urolithiasis in rat.

A large population is suffering from multifactorial urolithiasis worldwide with a reoccurrence rate of almost 70%-80% in males and 47%-60% in females. In the present study, the nephroprotective effect of silver nanoparticles (AgNPs) synthesised by Bryophyllum pinnatum was evaluated in ethylene glycol-induced urolithiasis in rat. B. pinnatum-mediated AgNPs which were found to be spherical and polydispersed particles with an average size of 32.65 nm determined by transmission electron microscopy analysis, and showing an absorption peak at 432 nm by the UV-Vis spectrophotometric analysis, revealing the role of hydroxyl group in the synthesis by Fourier Transformed Infrared Spectroscopy analysis, with a zeta potential value of -15.7 mV. The crystalline nature and fcc structure was demonstrated based on X-ray diffraction analysis. Animal study was performed on 36 male Wistar rats divided into six equal groups, which demonstrated significant increase in serum total protein, albumin and globulin and significant decrease in AST, ALT, creatinine, BUN, calcium and phosphorus in group V and VI when compared with group II and IV. No crystalluria was observed in rats given B. pinnatum AgNPs. Histopathological observations in group V and VI showed mild degenerative changes and restoration or maintenance of kidney parenchyma when compared with group II and IV rats. Thus, the authors conclude with the beneficial preventive and therapeutic nephroprotective effect of B. pinnatum-mediated AgNPs against ethylene glycol-induced urolithiasis in rats.

Protective effect of apigenin on ethylene glycol-induced urolithiasis via attenuating oxidative stress and inflammatory parameters in adult male Wistar rats.

AIMS: Apigenin (4',5,7-trihydroxyflavone) is one of the subclasses of flavonoids and has various pharmacological effects. The present work was carried out to study the effect of apigenin on ethylene glycol-induced kidney damage in male Wistar rats. MAIN METHODS: We evaluated the effects of apigenin orally administrated in normal and urolithiatic rats. Animals were assigned to nine groups in random: normal control; apigenin alone (0.005, 0.01, and 0.02 g/kg bw); urolithiatic control (0.75% ethylene glycol and 1.0% ammonium chloride in drinking water); apigenin (0.005, 0.01, and 0.02 g/kg bw) plus ethylene glycol and ammonium chloride; and cystone (0.75 g/kg bw) plus ethylene glycol and ammonium chloride. At the end of 28th day of treatment, animals were sacrificed for biochemical and histopathological assays. KEY FINDINGS: Our results indicated that the apigenin treatment decreased the formation of urinary stones in urolithiatic rats. Also, apigenin reduced the generation of malondialdehyde and enhanced antioxidant enzymes activities in the kidney homogenate of rats. It also caused a significant decrease in the calcium oxalate crystals numbers in urinary sample of rats with ethylene glycol-induced hyperoxaluria. These findings were supported by histopathological examinations. SIGNIFICANCE: Based on the results obtained, apigenin attenuate ethylene glycol-related kidney damage in male Wistar rats. Although the underlying mechanism of apigenin effect has not been determined, reduction of urinary levels of stone-producing constituents, antioxidant activities, and inhibition of TGF-ß signaling may be involved.

Antilithiatic activity of a non-pharmacopoeial Unani formulation in chemically induced urolithiasis in rats.

OBJECTIVES: Parshioshan (Adiantum capillus-veneris L.), Duqu (Peucedanum grande C.B. Clarke), Kaknaj (Physalis alkekengi L.) and Kharekhasak (Tribulus terresteris L.) have been selected for this study as they have been associated with medicinal actions for litholytic activity. METHODS: The experiment was carried out in Sprague Dawley rats divided into seven groups, serving as plain control, disease control, standard control, curative A and B and preventive A and B groups. Animals of plain control received distilled water. Remaining six groups received Ethylene glycol 0.75% and Ammonium chloride 1% by adding in the drinking water for the first three days followed by 0.75% Ethylene glycol for 18 days. From 8th day till 21st day, standard control received Cystone in the dose of 750 mg/kg. Preventive and curative test groups were treated with hydroalcoholic extract of the test drug in the dose of 132 mg/kg and 264 mg/kg from 1st to 21st day and 8th to 21st day of calculi induction. RESULTS: Test drug reduced the number of calcium oxalate crystals in the urine; the level of urinary calcium, creatinine, magnesium, phosphorus, sodium and chloride decreased significantly in standard and test groups. The urine volume increased significantly in all the test groups. The level of serum calcium, urea, phosphorus and creatinine were significantly reduced in all the test groups. CONCLUSIONS: These results indicated that the test drug reduced and prevented the growth of urinary stones. Moreover, the test drug also possessed significant antiurolithiatic activity. However, the protective effect was found more than its curative effect.

Association of urate-lowering drugs with the risk of future urolithiasis in patients with gout: A population-based nested case-control study.

BACKGROUND: Patients with gout have an increased risk of urolithiasis and usually need urate-lowering therapy (ULT) for the prevention of disease progression. However, there is a paucity of clinical data regarding the risk of future urolithiasis in ULT users. METHODS: This nested case-control study was performed using the Taiwan National Health Insurance Research Database. The aim of this study was to examine whether ULT (xanthine oxidase inhibitors [XOIs] or uricosuric agents) is associated with risk of future urolithiasis in patients with gout. Data were collected from January 2000 to December 2012. RESULTS: This study included 2307 case patients and 2307 matched controls. Case patients had gout that developed into urolithiasis, and control patients had gout but were not diagnosed with urolithiasis during the study period. Patients had a mean age of 56.3 years at diagnosis of gout, and 83.2% were male patients. No association was detected between use of XOIs or uricosuric agents and risk of future urolithiasis. Furthermore, there was no significant difference in the risk of future urolithiasis in patients exposed to various cumulative days of XOI or uricosuric prescriptions. CONCLUSION: The present study provides evidence that neither XOIs nor uricosuric agents are associated with risk of future urolithiasis in patients with gout. Before the availability of more clinical evidence, ensuring high fluid intake and prospective monitoring of urolithiasis development are still important for uricosuric agent users.