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.

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.

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.

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.

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.

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.

Antioxidant and Polyphenol-Rich Ethanolic Extract of Rubia tinctorum L. Prevents Urolithiasis in an Ethylene Glycol Experimental Model in Rats.

Treatment of kidney stones is based on symptomatic medications which are associated with side effects such as gastrointestinal symptoms (e.g., nausea, vomiting) and hepatotoxicity. The search for effective plant extracts without the above side effects has demonstrated the involvement of antioxidants in the treatment of kidney stones. A local survey in Morocco has previously revealed the frequent use of Rubia tinctorum L. (RT) for the treatment of kidney stones. In this study, we first explored whether RT ethanolic (E-RT) and ethyl acetate (EA-RT) extracts of Rubia tinctorum L. could prevent the occurrence of urolithiasis in an experimental 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC)-induced rat model. Secondly, we determined the potential antioxidant potency as well as the polyphenol composition of these extracts. An EG/AC regimen for 10 days induced the formation of bipyramid-shaped calcium oxalate crystals in the urine. Concomitantly, serum and urinary creatinine, urea, uric acid, phosphorus, calcium, sodium, potassium, and chloride were altered. The co-administration of both RT extracts prevented alterations in all these parameters. In the EG/AC-induced rat model, the antioxidants- and polyphenols-rich E-RT and EA-RT extracts significantly reduced the presence of calcium oxalate in the urine, and prevented serum and urinary biochemical alterations together with kidney tissue damage associated with urolithiasis. Moreover, we demonstrated that the beneficial preventive effects of E-RT co-administration were more pronounced than those obtained with EA-RT. The superiority of E-RT was associated with its more potent antioxidant effect, due to its high content in polyphenols.

Anti-urolithiatic activity of Salvia hispanica L. seeds in ethylene glycol induced urolithiasis rat's model.

Urolithiasis is a disorder of kidneys in which stones formation occur due to the excessive deposition of minerals in the urinary tract. It affects 12% of the population worldwide. Salvia hispanica seeds are rich source of quercetin which has preventive role in renal stone formation. The study objective was to explore scientifically the anti-urolithiatic effect of Salvia hispanica seed's methanol extract using in vitro and in vivo urolithiasis models. For in-vitro study nucleation, growth and aggregation assays were performed. In vivo study was performed on rats and they were divided into six groups (n=6). Group-I was given vehicle only. Group-II was disease control, treated with 0.75% EG in drinking water which triggered urolithiasis. Groups-III received cystone (750 mg/kg, orally). Groups IV-VI were treated with extract at 100, 300 and 700 mg/kg doses orally once daily. Groups III-VI additionally received 0.75% EG in drinking water. In vitro study revealed concentration dependent increase in percentage inhibition of crystal's nucleation, growth and aggregation. In vivo study revealed anti-urolithiatic activity by lowering oxalate, calcium, phosphate, sodium and potassium levels in the urine and the serum uric acid, blood urea nitrogen, total proteins and total albumin. Salvia hispanica seeds are good alterative of allopathic anti-urolithiatic drugs to treat urolithiasis.

Evaluation of diuretic efficacy and antiurolithiatic potential of ethanolic leaf extract of Annona squamosa Linn. in experimental animal models.

OBJECTIVE: The study is to investigate the diuretic and antiurolithiatic activities of ethanolic leaf extract of Annona squamosa Linn. in experimental animals. MATERIALS AND METHODS: For both studies, Wistar albino rats and two doses of extract (250 and 500 mg/kg) were used. Diuretic activity was evaluated by Lipschitz model. Urine volume and urine pH were noted, the concentration of sodium and potassium was estimated by flame photometry, and diuretic index, natriuretic index, and Lipschitz values were calculated from the results. Furosemide was used as a positive control. Ethylene glycol-induced urolithiasis model was used for antiurolithiatic study. Urine volume, urine pH, body weight, and biochemical parameters such as calcium, urea, uric acid, and creatine both from serum and urine were estimated. Antioxidant parameters and histopathological analysis of the kidney were evaluated. Cystone was used as a positive control in this study. Results were expressed as mean ± standard error of mean. Statistical analysis was carried out using one-way analysis of variance, followed by Dunnett's multiple comparison tests. RESULTS: In both diuretic and antiurolithiatic studies, both doses of the extract showed efficacy, and the dose of 500 mg/kg has shown a significant effect compared to positive control and negative control. CONCLUSION: The dose of 500 mg/kg showed a promising diuretic and antiurolithiatic activity.

Anti-Inflammatory and Anti-Urolithiasis Effects of Polyphenolic Compounds from Quercus gilva Blume.

Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include relief of urolithiasis, tremors and inflammation. In the present study, the anti-urolithiasis activity including anti-inflammatory and anti-oxidative activities, of some phenolic compounds isolated from QGB were described. Seven compounds were isolated and identified as picraquassioside D (1), quercussioside (2), (+)-lyoniresinol-9'α-O-ß-d-xylopyranoside (3), (+)-catechin (4), (-)-epicatechin (5), procyanidin B-3 (6), and procyanidin B-4 (7). Compounds 5-7 showed potent anti-oxidative and anti-inflammatory activities. These compounds were further tested for their inhibition of the gene expression of the inflammatory cytokines. The three compounds 5-7 showed dose-dependent inhibitory activities on gene expression of COX-2 and IL-1ß. In vivo, urolithiasis was induced more effectively in an animal model of acute urolithiasis by the administration of QGB extract. These results indicate the potential of compounds from QGB in the treatment of urolithiasis.

Potential therapeutic activity of Phlogacanthus thyrsiformis Hardow (Mabb) flower extract and its biofabricated silver nanoparticles against chemically induced urolithiasis in male Wistar rats.

Urolithiasis is a painful disorder in which stones are formed in the kidney, bladder or urethra. There are no proper therapeutic treatments available for kidney stones and people suffering from larger stones have to undergo surgery which has many side effects. A natural remedy with therapeutic effects that can dissipate and remove even the larger stones would eliminate the need of a surgery and the risks associated with it. The flowers of Phlogacanthus thyrsiformis used in culinary recipes in the north eastern India are also widely used as a folklore medicine for the treatment of kidney stones and liver disorders. The aim of this study was to evaluate the prophylactic and therapeutic activity of the aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles against struvite urinary stones and calcium oxalate kidney stones. A kidney stone inhibition study was carried out on struvite stones grown in gel medium and calcium oxalate stones in rat models using an aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles. The aqueous extract of P. thyrsiformis flowers and their biofabricated silver nanoparticles, obtained by a green synthetic method, were used to treat struvite urinary stones in vitro and calcium oxalate kidney stones in vivo. Struvite stones were grown in tubes by gel diffusion technique and were treated with varying concentrations of the extract and its nanoparticles. The size of the struvite stones was monitored for 96h using a travelling microscope. Calcium oxalate stones were induced in male Wistar rats by feeding ethylene glycol-ammonium chloride mixture for 14days. Both, prophylactic and therapeutic activities were evaluated by analyzing the urine, serum and histopathological parameters of the rats. The qualitative screening of water extract unveiled the presence of flavonoids as a major constituent. Both, the extract and the nanoparticles effectively reduced the size of struvite stones in vitro and eliminated calcium oxalate stones in Wistar rats in vivo. The potent therapeutic activity of both extract and silver nanoparticles was observed as compared to preventive activity. Anti-urolithiatic potency can be attributed to the presence of flavonoids.

Antiurolithic effect of olive oil in a mouse model of ethylene glycol-induced urolithiasis.

PURPOSE: At present, commercially available antiurolithic drugs have more adverse effects than potential therapeutic or preventive effects with chronic use. With this in mind, the present study was designed to assess the antiurolithic effect of olive oil in a mouse model of ethylene glycol (EG)-induced urolithiasis. MATERIALS AND METHODS: Adult albino mice were divided into 6 groups. Group I was fed the vehicle only. Group II was supplemented with 0.75% EG alone in drinking water during the experimental period to initiate deposition of calcium oxalate in kidneys, which leads to urolithiasis in animals. Groups III (olive oil control group) through V were fed olive oil orally at various doses during the experimental period. Group VI received cystone (750 mg/kg). Groups IV-VI additionally received 0.75% EG in drinking water ad libitum. SPSS ver.17.0 was used for statistical analysis. RESULTS: The study results showed significantly higher levels of serum urea, uric acid, and creatinine (p<0.05) in group II than in groups III-VI and I. Administration of olive oil at different doses restored the elevated serum parameters in groups IV and V compared with group II. Urine and kidney calcium, oxalate, and phosphate levels in groups IV-VI were significantly lower (p<0.05) than in animals with EG-induced urolithiasis (group II). Group V mice showed a significant restoration effect on serum as well as urine and kidney parameters compared with group II. CONCLUSIONS: Supplementation with olive oil (1.7 mL/kg body weight) reduced and prevented the growth of urinary stones, possibly by inhibiting renal tubular membrane damage due to peroxidative stress induced by hyperoxaluria.

Antiurolithiasis Activity of Bioactivity Guided Fraction of Bergenia ligulata against Ethylene Glycol Induced Renal Calculi in Rat.

Dried rhizome of Bergenia ligulata (pashanbhed) is commonly used as a traditional herbal medicine with a wide range of therapeutic applications including urolithiasis. Aqueous extract of B. ligulata was prepared through maceration followed by decoction (mother extract, 35.9% w/w). Further, polarity based fractions were prepared successively from mother extract which yielded 3.4, 2.9, 5.4, 7.5, and 11.3% w/w of hexane, toluene, dichloromethane (DCM), n-butanol, and water fractions, respectively. The in vitro, ex vivo, and real-time antiurolithiasis activity of mother extract and fractions were carried out using aggregation assay in synthetic urine and in rat plasma. The study revealed that DCM fraction has significantly (p < 0.05) greater inhibitory potential than other fractions. Ethylene glycol in drinking water (0.75%, v/v) for 28 days was used for induction of urolithiasis and the curative effects of mother extract and DCM fraction were checked for the level of oxalate, calcium, creatinine, uric acid, and urea of both urine and serum. Treatment with mother extract and DCM fraction at a dose of 185 mg/kg and 7 mg/kg, respectively, in ethylene glycol induced rats resulted in a significant (p < 0.05) decrease in serum and urine markers. Histological study revealed lower number of calcium oxalate deposits with minimum damage in the kidneys of mother extract and DCM fraction treated rats. This result provides a scientific basis for its traditional claims.

Do Calcium Supplements Predispose to Urolithiasis?

PURPOSE OF REVIEW: The purpose of this study was to investigate the role of calcium supplements, with or without vitamin D, in urinary stone formation in healthy population and in osteoporotic patients as well. Moreover, this review aims to clarify whether or not, and above which dose, they are associated with the risk of lithiasis. RECENT FINDINGS: A research in Medline, Embase, and Scopus databases up to September 2015 was conducted using the following keywords: calcium, supplements, vitamin D, complications, lithiasis, and urinary stone. All types of studies were taken into account (cohort studies, reviews, meta-analyses), and in case they fulfilled the inclusion criteria, they were included in our review. The analysis of the data showed that calcium supplements, probably in association with anti osteoporotic treatment, do not create a predisposition towards lithiasis formation among women suffering from osteoporosis, neither among non-osteoporotic older men. In healthy postmenopausal as well as younger women, the supplements might increase susceptibility to urinary stone formation in long-term basis. The consumption of calcium supplements with the meals could play a protective role in women and younger males. There is certain evidence that supplements containing citrate may be more beneficial over the rest of calcium supplements, particularly when consumed during the meal. Osteoporotic women and healthy men are not at risk of stone formation. On the contrary, healthy women should be aware of the potential risk of developing urinary lithiasis in long-term basis.

Chenopodium album Linn. leaves prevent ethylene glycol-induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Chenopodium album Linn. are traditionally used for correction of kidney diseases and urinary stones. The present work investigated the effect of methanolic and aqueous extracts of leaves of Chenopodium album on experimentally-induced urolithiasis in rats to substantiate its traditional use as antilithiatic agent. MATERIALS AND METHODS: The leaf extract was standardized by HPLC. Urolithiasis was induced in rats by administration of 0.75% v/v of ethylene glycol (EG) in distilled water and in addition, vehicle or methanol (CAME) or aqueous (CAAE) extract of the leaves of Chenopodium album each in the dose 100, 200 and 400mg/kg or Cystone (750mg/kg) were administered daily orally for 28 days. Urolithiasis was assessed by estimating the calcium, phosphorus, urea, uric acid, and creatinine in both urine and plasma. The volume, pH and oxalate levels were also estimated in urine. The renal oxalate content was estimated in kidney while calcium oxalate deposits were observed histologically. RESULTS: The treatment with CAME or CAAE for 28 days significantly attenuated the EG-induced elevations in the urine and plasma levels of calcium, phosphorus, urea, uric acid and creatinine along with decrease in urine volume, pH and oxalates. The treatments also decreased renal tissue oxalate and deposition of oxalate crystals in kidney due to EG treatment. The effects of CAME and CAAE were comparable to standard antilithiatic agent, cystone. The findings indicate the preventive effect of CAME and CAAE which can be due to inhibitory effect on crystallization and stone dissolution. The effect was attributed to the presence of phytochemicals like flavonoids and saponins. CONCLUSION: In conclusion, Chenopodium album leaves exhibited antilithiatic effect and validates its ethnomedicinal use in urinary disorders and kidney stones.

Alteration in Oxidative/nitrosative imbalance, histochemical expression of osteopontin and antiurolithiatic efficacy of Xanthium strumarium (L.) in ethylene glycol induced urolithiasis.

Xanthium strumarium has traditionally been used in the treatment of urolitiasis especially by the rural people in India, but its antiurolithiatic efficacy was not explored scientifically till now. Therefore, the present study was designed to validate the ethnic practice scientifically, and explore the possible antiurolithiatic effect to rationalize its medicinal use. Urolitiasis was induced in hyperoxaluric rat model by giving 0.75% ethylene glycol (EG) for 28days along with 1% ammonium chloride (AC) for first 14days. Antiurolithiatic effect of aqueous-ethanol extract of Xanthium strumarium bur (xanthium) was evaluated based on urine and serum biochemistry, oxidative/nitrosative stress indices, histopathology, kidney calcium and calcium oxalate content and immunohistochemical expression of matrix glycoprotein, osteopontin (OPN). Administration of EG and AC resulted in hyperoxaluria, crystalluria, hypocalciuria, polyurea, raised serum urea, creatinine, erythrocytic lipid peroxidise and nitric oxide, kidney calcium content as well as crystal deposition in kidney section in lithiatic group rats. However, xanthium treatment significantly restored the impairment in above kidney function test as that of standard treatment, cystone. The up-regulation of OPN was also significantly decreased after xanthium treatment. The present findings demonstrate the curative efficacy of xanthium in ethylene glycol induced urolithiasis, possibly mediated through inhibition of various pathways involved in renal calcium oxalate formation, antioxidant property and down regulation of matrix glycoprotein, OPN. Therefore, future studies may be established to evaluate its efficacy and safety for clinical use.