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.

Urine cadmium and urolithiasis: A systematic review and meta-analysis.

Exposure to cadmium may increase risk of urolithiasis, but the results remain inconclusive. This systematic review and meta-analysis aimed to access the association between cadmium exposure and urolithiasis. We searched Medline/PubMed, Embase, Web of Science Core Collection, and Cochrane Central for studies. The primary outcome was the incidence of urolithiasis compared to reference groups. We used relative risk as the summary effect measure. This meta-analysis included eight observational studies and divided into 39 study populations. Among 63,051 subjects, 5018 (7.96%) individuals had urolithiasis. The results indicated that people with an increment of 0.1 µg/g creatinine in urinary cadmium had a 2% increased risk of urolithiasis (pooled relative risk [RR], 1.02; 95% confidence interval [CI], 1.01-1.03) and there is no difference in the risk of urolithiasis in high and low cadmium exposure levels. Meanwhile, people with an increment of 0.1 µg/L in urinary cadmium had a 4% increased risk of urolithiasis (pooled RR, 1.04; 95% CI, 1.02-1.07). Our findings also showed similar associations in both sex, different region (Sweden, China, and Thailand), general and occupational population. The results indicate that cadmium exposure was significantly associated with an elevated risk of urolithiasis. Therefore, it is imperative to take steps to minimize cadmium exposure.

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.

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.

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).

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.

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.

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.

Nephroprotective Effect of Pleurotus ostreatus and Agaricus bisporus Extracts and Carvedilol on Ethylene Glycol-Induced Urolithiasis: Roles of NF-κB, p53, Bcl-2, Bax and Bak.

This study was designed to assess the nephroprotective effects of Pleurotus ostreatus and Agaricus bisporus aqueous extracts and carvedilol on hyperoxaluria-induced urolithiasis and to scrutinize the possible roles of NF-κB, p53, Bcl-2, Bax and Bak. Phytochemical screening and GC-MS analysis of mushrooms' aqueous extracts were also performed and revealed the presence of multiple antioxidant and anti-inflammatory components. Hyperoxaluria was induced in Wistar rats through the addition of 0.75% (v/v) ethylene glycol in drinking water for nine weeks. The ethylene glycol-administered rats were orally treated with Pleurotus ostreatus and Agaricus bisporus aqueous extracts (100 mg/kg) and carvedilol (30 mg/kg) daily during the last seven weeks. The study showed that Pleurotus ostreatus, Agaricus bisporus and carvedilol all successfully inhibited ethylene glycol-induced histological perturbations and the elevation of serum creatinine, serum urea, serum and urinary uric acid, serum, urinary and kidney oxalate, urine specific gravity, kidney calcium, kidney NF-κB, NF-κB p65, NF-κB p50, p53, Bax and Bak expressions as well as serum TNF-α and IL-1ß levels. Moreover, the treatment decreased the reduction in urinary creatinine, urinary urea, ratios of urinary creatinine to serum creatinine and urinary urea to serum urea, Fex Urea and Bcl-2 expression in kidney. In conclusion, although Pleurotus ostreatus and Agaricus bisporus extracts and carvedilol all significantly inhibited the progression of nephrolithiasis and showed nephroprotective effects against ethylene glycol-induced kidney dysfunction, Pleurotus ostreatus and Agaricus bisporus seemed to be more effective than carvedilol. Moreover, the nephroprotective effects may be mediated via affecting NF-κB activation, extrinsic apoptosis and intrinsic apoptosis pathways.

iTRAQ-Based Comparative Proteomics Analysis of Urolithiasis Rats Induced by Ethylene Glycol.

Nephrolithiasis is a frequent chronic urological condition with a high prevalence and recurrence rate. Proteomics studies on urolithiasis rat models are highly important in characterizing the pathophysiology of kidney stones and identifying potential approaches for preventing and treating kidney stones. The isobaric tags for relative and absolute quantification (iTRAQ) were performed to identify differentially expressed proteins (DEPs) in the kidney between urolithiasis rats and control rats. The results showed that 127 DEPs (85 upregulated and 42 downregulated) were identified in urolithiasis and control rats. The functions of DEPs were predicted by Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis. The expression of four upregulated proteins (Tagln, Akr1c9, Spp1, and Fbn1) and four downregulated proteins (Hbb, Epb42, Hmgcs2, and Ca1) were validated by parallel reaction monitoring (PRM). Proteomics studies of ethylene glycol-induced urolithiasis rat models using iTRAQ and PRM helped to elucidate the molecular mechanism governing nephrolithiasis and to identify candidate proteins for the treatment of kidney stones.

Exposure to imipenem/cilastatin causes nephrotoxicity and even urolithiasis in Wistar rats.

Imipenem/cilastatin is a broad-spectrum ß-lactam antibiotic used to treat several bacterial infections. The present study was designed to validate the nephrotoxic effect of this drug in rats and to explore its potentional urolithiatic effect. Thirty two Wistar rats were randomly divided into four groups: three experimental groups treated with different imipenem/cilastatin dosages (30, 50 and 80 mg/kg/day) and a control group.The experimental groups were given intraperitoneal imipenem/cilastatin injections twice daily for 7 days, and the control group was given intraperitoneal vehicle NaCl 0.9% solution. Nephrotoxic effect of this antibiotic was assessed based on urine and plasma biochemistry, oxidative stress parameters, histopathological examination and infrared spectroscopy characterization. Imipenem/cilastatin administration resulted in alkaline urine, polyuria, crystalluria, raised plasma levels of urea, creatinine and uric acid, decreased contents of plasma gamma glutamyltranspeptidase and alkaline phosphatase, oxidative stress status, malpighian metaplasia as well as crystal deposition in kidneys and urinary tracts of Wistar rats. In addition, the precise nature of the calculi was identified, being formed by imipenem/cilastatin, thus confirming their iatrogenic origin. In conclusion, this study demonstrated through rat model that subacute exposure to imipenem/cilastatin may induce nephrotoxicity and increase the risk for developing kidney stones even at therapeutic dose levels in a dose-dependent manner.