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.

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.

Evaluations of the curative efficacy of G. fruticosus solvent extracts in experimentally induced nephrolithiatic Wistar male rats.

BACKGROUND: In Ethiopian folk medicine, there is a claim that medicinal plants can treat urolithiasis although there is insufficient scientific evidence. The objective of this study was to evaluate the curative efficacy of Gomphocarpus fruticosus extracts in experimentally induced nephrolithiatic rats. METHODS: Urolithiasis was induced in male Wistar rats by feeding ethylene glycol in drinking water for 28 days. The curative effects were evaluated after oral administrations of 200 mg/kg of the extracts from 15 to 28 days. Urine samples were collected 1 day before sacrificing the rats. Blood, liver and kidney samples were gathered under anaesthetic condition at day 28. Crystals in the urine were also analyzed by light microscopy. RESULTS: G. fruticosus EtOAc extract reduced significantly the level of sodium (P < 0.001), whereas it was significantly elevated the levels of magnesium and citrate (P < 0.01) compared to lithiatic control. G. fruticosus BuOH extract lowered the levels of potassium (P < 0.01), calcium and phosphate in urolithiatic rats. It was also observed that G. fruticosus EtOAc extract decreased the level of oxalate in the urine (P < 0.001), whereas it was increased the levels of magnesium (P < 0.05) and citrate (P < 0.01) in serum analysis after exposure to BuOH extract. In the kidneys, CaOx crystal deposits were reduced significantly by G. fruticosus EtOAc extract (P < 0.01). CONCLUSION: It has been noted that G. fruticosus EtOAc extract was potent in treating urolithiasis. However, further study is required to assess the efficacy of the active compounds against urolithiasis.

Antiurolithic efficacy of a phenolic rich ethyl acetate fraction of the aerial parts of Aerva lanata (Linn) Juss. ex Schult. in ethylene glycol induced urolithic rats.

OBJECTIVES: The study was carried out to evaluate the in vivo antiurolithic efficaciousness of an ethyl acetate fraction of Aerva lanata (EAFAL) derived from the hydromethanolic extract of its aerial parts (HMEAL). METHODS: In vivo pharmacological potency of EAFAL was assessed by ethylene glycol (EG) induced urolithiasis model in male Wistar albino rats. Urine samples of the animals were analysed for physical parameters, stone promoters, inhibitors along with an evaluation of the biochemical parameters of serum and kidneys. Histopathological investigation of the kidneys was done. The fraction was further subjected to LC-MS and HPLC for its phytochemical evaluation. KEY FINDINGS: EAFAL demonstrated a significant antiurolithic effect by a restoration of the balance between urinary promoters and inhibitors along with an amelioration of the urinary pH. The abnormally elevated levels of serum nitrogenous substances, calcium, albumin, globulin, total protein along with altered renal calcium, oxalate and uric acid were also alleviated significantly followed by an improvement of the histopathological aberrancies. Phytochemical analysis showed evidence of phenolic components and flavonoids. CONCLUSIONS: The current findings prove the beneficial role of phenolic and flavonoid rich EAFAL in ameliorating urolithiasis induced abnormalities of urine, serum and kidneys.

Oxidative stress and endoplasmic stress in calcium oxalate stone disease: the chicken or the egg?

Crystal modulators play a significant role in the formation of calcium oxalate stone disease. When renal cells are subjected to oxalate stress, the loss in cell integrity leads to exposure of multiple proteins that assist and/or inhibit crystal attachment and retention. Contact between oxalate and calcium oxalate with urothelium proves fatal to cells as a result of reactive oxygen species generation and onset of oxidative stress. Hence, as a therapeutic strategy it was hypothesised that supplementation of antioxidants would suffice. On the contrary to popular belief, the detection of oxalate induced endoplasmic reticulum mediated apoptosis proved the ineffectiveness of antioxidant therapy alone. Thus, the inadequacy of antioxidant supplementation in oxalate stress invoked the presence of an alternative pathway for the induction of kidney fibrosis in hyperoxaluric rats. In addition to settling this query, the link between oxidative stress and ER stress is not well understood, especially in urolithiasis.

Identification of Novel Human Serum Albumin (SA) Inhibitors from Scoparia Dulsis for Urolithiasis.

BACKGROUND: Urolithiasis is the process of forming stones in the kidney, bladder, and/or urinary tract. It has been reported that kidney stones are the third most common disorder among urinary diseases. At present, surgical procedures and Extracorporeal Shock Wave Lithotripsy (ESWL) are commonly employed for the treatment of Urolithiasis. The major drawback of these procedures is the recurrence of stones. METHODS: This study aimed to identify potential natural inhibitors against human Serum Albumin (SA) from the plant Scoparia Dulsis for Urolithiasis. As protein-ligand interactions play a key role in structure- based drug design, this study screened 26 compounds from Scoparia Dulsis and investigated their binding affinity against SA by using molecular docking. The three dimensional (3D) structure of SA was retrieved from Protein Data Bank (PDB) and docked with PubChem structures of 26 compounds using PyRX docking tool through Autodock Vina. Moreover, a 3D similarity search on the PubChem database was performed to find the analogs of best scored compound and docking studies were performed. Drug-likeness studies were made using Swiss ADME and Lipinski's rule of five was performed for the compounds to evaluate their anti-urolithiatic activity. RESULTS: The results showed that citrusin c (Eugenyl beta-D-glucopyranoside) exhibited best binding energy of -8.1 kcal/mol with SA followed by aphidicolin, apigenin, luteolin and scutellarein. Two compounds (PubChem CID 46186820, PubChem CID 21579141) analogous to citrusin c were selected based on the lowest binding energy. CONCLUSION: This study, therefore, reveals that these compounds could be promising candidates for further evaluation for Urolithiasis prevention or management.

Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through -In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats.

Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.

Urinary sulfated glycosaminoglycan insufficiency and chondroitin sulfate supplement in urolithiasis.

Familial members of urolithiasis have high risk for stone development. We observed the low sulfated glycosaminoglycan (GAG) excretion in urolithiasis patients and their descendants. In this study, we investigated urinary excretion of sulfated GAG, chondroitin sulfate (CS), heparan sulfate (HS) and hyaluronic acid (HA) in urolithiasis and their children, and explored the effect of CS and HA supplement in urolithic hyperoxaluric rats. The 24-hour urines were collected from urolithiasis patients (28) and their children (40), as well as healthy controls (45) and their children (33) to measure urinary sulfated GAG, CS, HS and HA excretion rate. Our result showed that urinary sulfated GAG and CS were diminished in both urolithiasis patients and their children, while decreased HS and increased HA were observed only in urolithiasis patients. Percentage of HS per sulfated GAG increased in both urolithiasis patients and their children. In hyperoxaluric rats induced by ethylene glycol and vitamin D, we found that CS supplement could prevent stone formation, while HA supplement had no effect on stone formation. Our study revealed that decreased urinary GAG and CS excretion are common in familial members of urolithiasis patients, and CS supplement might be beneficial in calcium oxalate urolithiasis prophylaxis for hyperoxaluric patients.

Lime powder regimen supplement alleviates urinary metabolic abnormalities in urolithiasis patients.

BACKGROUND: Urolithiasis has high recurrent rate after surgical removal within 3 years. Potassium citrate compound is used to prevent stone recurrence but it has intolerable gastrointestinal adverse effects. We conducted a phase 2 clinical study of lime power regimen (LPR), a limeade-based supplement containing potassium and citrate for 6 months period of treatment, to evaluate its effects on biochemical and clinical aspects of recurrent urolithiasis. METHODS: Seventy-four urolithiasis patients were randomly allocated to receive either LPR or placebo for 6 months in a double-blinded manner. Plasma and 24 h urine samples were collected to measure urinary pH, mineral excretion and urinary total antioxidant status , plasma for creatinine and plasma protein carbonyl, and stone for elemental analysis at the initiation and end-of-treatment (6 month). Adverse effects were recorded. RESULTS: Administration of LPR significantly increased urinary pH, citrate and potassium excretion. Urinary levels of calcium and oxalate, and plasma protein carbonyl content were reduced, while urinary total antioxidant status was elevated by LPR treatment. Urinary supersaturation was decreased and urinary protein excretion was ameliorated in LPR-treated patients. Gastrointestinal adverse effects were rarely observed. None of the participants developed stone recurrence for the duration of the trial. CONCLUSION: Lime power regimen is a potential drug to correct urinary metabolic disorders associated with urolithiasis in high risk stone recurrent patients. A phase 3 clinical trial is underway to validate anti-stone recurrence property of LPR in long-term treatment.

Endothelium corneum gigeriae galli extract inhibits calcium oxalate formation and exerts anti-urolithic effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine is preferred because of its safety and minimal/reduced side effects. Endothelium Corneum Gigeriae Galli (ECGG) extract, a traditional Chinese drug consisting of the dried gizzard membrane of Gallus gallus domesticus Brisson, was assessed for its effects and mechanism on urolithiasis. AIMS OF STUDY: To evaluate the effects of ECGG extract on calcium oxalate (CaOx) crystal formation in vitro, and assess the anti-urolithic effects of ECGG extract in vivo and explore the underlying mechanism. MATERIALS AND METHODS: In vitro, CaOx crystals were treated with ECGG extract (0.05, 0.2, and 0.8 g/mL), and assessed by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and electrical conductivity. Then, a rat model of renal calculi was established by ethylene glycol and ammonium chloride treatment, and ECGG extract (5.0, 10.0 and 20.0 g/kg) was administered orally. After treatment, urine, serum and kidney bioindicators were analyzed, as well as kidney's pathological features. RESULTS: In the presence of ECGG extract, calcium oxalate dihydrate (COD) crystals with typical tetragonal bipyramidal morphology were obtained; meanwhile, the formation of calcium oxalate monohydrate (COM), a major urinary stone component, was inhibited; in addition, the equilibration time of the chemical reaction of Ca2+ and C2O42- ions was delayed in a concentration dependent manner. ECGG extract actually showed anti-urolithic effects; the incidence rates of crystal formation in the kidney in the model, low, middle and high dose groups were 100%, 90%, 70% and 60%, respectively, with a dose-dependent alleviation of kidney stone amounts and kidney damage. Treatment with middle and high ECGG extract doses significantly decreased urine uric acid and oxalic acid amounts, serum creatinine, urea nitrogen and uric acid contents, and kidney tissue oxalic acid and calcium levels, while increasing kidney and urinary magnesium and superoxide dismutase levels (P < 0.05). CONCLUSION: ECGG extract has outstanding anti-urolithic effects, potentially with included bioorganic molecules inducing COD crystal nucleation and growth. Therefore, ECGG extract is a promising drug for preventing and treating urolithiasis.

The role of zinc in urinary stone disease.

In recent years, the role of trace elements in lithogenesis has received steadily increasing attention. It is well documented that some trace elements can influence the morphology and speed of the crystallization process. Zinc has been found in significant amounts in calcium stones relative or organic stones (uric acid and cystine), probably substituting calcium in crystals because of their similarity in charge and size. High Zn levels are present in carbapatite of Randal's plaques suggesting that zinc could promote calcium phosphate deposition in the medullar interstitium. Large-scale epidemiological studies have found an association of increased dietary zinc intake with increased risk of nephrolithiasis in adults but not in adolescents. Most studies examining urinary zinc levels in adults have reported increased urinary Zn excretion in stone formers. In an experimental model of organic crystal formation produced by silencing xanthine dehydrogenase in Drosophila fly, maneuvers that reduce Zn excretion have shown to reduce crystal formation in the lumen of the Malpighian tubules. This is curious because this is not a model of calcium stone formation. Finally, zinc supplementation has been associated with increased admissions for urinary lithiasis in men, but no change in calcium stone formation in children. Perhaps, some of these contradicting findings can be explained in part by the in vitro effect of zinc on the type and amount of calcium phosphate formed: At low concentrations, Zn inhibited the crystal growth of dicalcium phosphate dihydrate, octacalcium phosphate, and apatite, and at higher concentrations, it promoted the formation of amorphous calcium phosphate. Thus, further studies are needed to see whether manipulation of Zn metabolism can inhibit calcium stone formation.

Evaluation of in vitro and in vivo anti-urolithiatic activity of silver nanoparticles containing aqueous leaf extract of Tragia involucrata.

The present investigation is focused on exploring the anti-urolithiatic potential of aqueous leaf extract of Tragia involucrata (TIA) and its silver nanoparticles (AgNPs) and to quantify the total phenol, flavonoid, terpenoid and sterol contents present in TIA. Quantification results suggested TIA to be a rich source of phenol, flavonoid and terpenoid and less of sterol content. The AgNPs were synthesized by a simple green method using aqueous extract of T. involucrata. The formation of AgNPs was confirmed through UV spectroscopy, particle size analysis, zeta potential, X-ray diffraction and transmission electron microscopy. The in vitro struvite growth inhibitory activity of the extract was performed using a single gel diffusion method. Samples incorporated with higher concentration of 2% TIA and AgNPs (200 µg mL-1) exhibited potent crystal growth inhibitory activity which was further supported by the dissolution of crystals in gel medium. Calcium oxalate stone formation was induced in rats by the oral administration of ethylene glycol in water. Stone formation was assessed by increase in the levels of calcium and phosphorous in the urine and accumulation of nitrogenous substances like urea, creatinine in renal tissues and blood. Prophylactic treatment with TIA and AgNPs showed significant anti-urolithiatic activity with normalization of the mineral contents of the urine and serum samples. Histopathological analysis of the kidney of TIA- and AgNP-treated animals showed no CaOx deposits and a normal architecture of the kidney cells. We conclude that aqueous extract of T. involucrata and its AgNPs has potential for the treatment of patients with recurrent stones.

α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria.

Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inhibits cystine stone formation in the Slc3a1-/- mouse model of cystinuria by increasing the solubility of urinary cystine. These findings identify a novel therapeutic strategy for the clinical treatment of cystinuria.

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.

Evaluation of protective effects of diosmin (a citrus flavonoid) in chemical-induced urolithiasis in experimental rats.

Context There have not been any conclusive studies of the effects of diosmin, a modified flavanone glycoside obtained from Teucrium gnaphalodes L'Her (Lamiaceae), on urolithiasis. Objective To evaluate anti-urolithiatic effects of diosmin in ammonium chloride and ethylene glycol-induced renal stone in experimental animals. Materials and methods Thirty Sprague-Dawley were divided into five groups (n=6) receiving the following treatments, respectively, p.o. for 15 consecutive days: distilled water, 0.75% v/v ethylene glycol + 2% w/v ammonium chloride, 0.75% v/v ethylene glycol + 2% w/v ammonium chloride + cystone® 750 mg/kg, 0.75% v/v ethylene glycol + 2% w/v ammonium chloride + diosmin 10 mg/kg or 0.75% v/v ethylene glycol + 2% w/v ammonium chloride + diosmin 20 mg/kg. Different biomarkers of urolithiasis in urine and serum were evaluated and histopathological examination of kidney was done. Results Animals treated with diosmin (both 10 and 20 mg/kg) had significantly (p < 0.005) decreased in kidney weight, urinary pH, total urinary protein, urinary calcium, phosphorus, serum potassium, sodium, magnesium, creatinine, uric acid and blood urea nitrogen levels and significantly (p < 0.005) increased in urinary volume, urinary magnesium, potassium, sodium, creatinine, uric acid and serum calcium levels in comparison to animals treated with ethylene glycol and ammonium chloride. However, results were better with diosmin 20 mg/kg in comparison to the control group. Conclusion Diosmin (10 and 20 mg/kg) has very good anti-urolithiatic activity similar to the standard drug cystone®.

Evaluation of antiurolithiatic and antioxidant potential of Lepidagathis prostrata: A Pashanbhed plant.

CONTEXT: Oxidative stress acts as an essential mediator in the pathophysiology of urolithiasis. Lepidagathis prostrata Dalz. (Acanthaceae) is a Pashanbhed plant that is recommended for the management of urolithiasis; however, no scientific validation has been reported. OBJECTIVES: To evaluate the antiurolithiatic and antioxidant potential of L. prostrata. MATERIALS AND METHODS: Methanol extract (LPM) and fractions; petroleum ether (LPPE), ethyl acetate (LPEA), n-butanol (LPBU) and aqueous (LPAQ) were prepared. In vitro antiurolithiatic activity was evaluated by the capacity to inhibit calcium oxalate (CaOx) nucleation and aggregation at different concentrations of extract/fractions (0.04-3 mg/mL) for 30 min. Total phenol and flavonoid content and antioxidant potential were determined. A validated HPTLC method was performed to quantify lupeol and ß-sitosterol. RESULTS: LPEA exhibited the highest dose-dependent inhibition of CaOx nucleation (IC50: 336.23 ± 30.79 µg/mL) and aggregation (IC50: 149.63 ± 10.31 µg/mL), which was significantly (p < 0.05) better than standard Cystone®. The polar LPBU fraction was enriched with phenols (47.34 ± 0.19 mg GAE/g) and flavonoids (20.38 ± 0.05 mg QE/g), which correlates with its highest antioxidant potential in DPPH, ABTS, nitric oxide scavenging and iron chelating activities (IC50: 1.18-87.34 µg/mL). To our knowledge, this is the first study reporting the presence of lupeol and ß-sitosterol in L. prostrata. CONCLUSION: The antiurolithiatic activity of L. prostrata is probably mediated through the inhibition of CaOx crystallization. In addition to its free radical scavenging and antioxidant activities, it would act as an excellent agent for the prevention of urolithiasis.

Anti-nephrolithic potential of catechin in melamine-related urolithiasis via the inhibition of ROS, apoptosis, phospho-p38, and osteopontin in male Sprague-Dawley rats.

The addition of melamine to infant formula may cause urolithiasis in humans and animals. This study examined the effects of catechin, an antioxidant, on melamine-cyanuric acid mixture (MCM)-induced crystallization in vitro and in vivo. In an in vitro study, crystal formation induced by an MCM was evaluated in media under various pH conditions and with catechin co-treatment. In an in vivo study, rats were administered an MCM (400 mg/kg, 1:1, via oral feeding tube) for four weeks and co-treated with catechin, after which crystal formation was observed. Oxidative stress biomarkers and nephrotoxicity were measured. Apoptotic cells were examined using the TUNEL assay. Phospho-p38 and osteopontin were evaluated via immunohistochemistry and Western blotting. MCM-induced crystal formation was pH-dependent in conditioned media, and catechin reduced the overall number of crystals. In the in vivo study, catechin suppressed MCM-induced protein expression and apoptosis in rats. Catechin consistently reduced the MCM-mediated production of renal malondialdehyde (MDA) and urinary 8-isoprostane (8-IP) in MCM-treated rats. The activities of antioxidant enzymes such as superoxide dismutase (SOD) were enhanced by catechin. Catechin consistently and significantly reduced levels of renal crystals and nephrotoxicity. Our findings suggest that catechin exhibits anti-nephrolithic potential by chemically inhibiting the formation of crystals and by inhibiting reactive oxygen species, apoptosis, phospho-P38, and osteopontin signaling in rats.

[REHABILITATION OF PATIENTS WITH URIC ACID AND MIXED UROLITHIASIS].

This paper presents evaluation of rehabilitation effectiveness of 113 patients aged 19-78 years diagnosed as having mixed and uric acid stones. 88 patients with uric acid stones 0,5-2,5 cm were assigned to group 1 and treated with Trometamol N parenteral litholis and a complex metaprophilaxis by dietary supplements Prolit and Urisan. 25 patients with mixed stones 1-3,5 cm were allocated to group 2 and treated with external shock wave lithotripsy and complex metaprophilaxis by dietary supplements Prolit Super Septo and Urisan. Positive results were achieved in all the patients. In the patients of group 1 the stones were completely dissolved. In group 2 treatment resulted in stone disintegration and clearance of small fragments 0,4 cm after partial dissolution.

[Urinary calculi and infection]. / Calcolosi urinaria e infezione.

Infection urinary stones resulting from urease-producing bacteria are composed by struvite and/or carbonate apatite. Bacterial urease splits urea and promotes the formation of ammonia and carbon dioxide leading to urine alkalinization and formation of phosphate salts. Proteus species are urease-producers, whereas a limited number of strains of other Gram negative and positive species may produce urease. Ureaplasma urealyticum and Corynebacterium urealyticum are urease-producers that are not isolated by conventional urine cultures, but require specific tests for identification. Primary treatment requires surgical removal of stones as complete as possible. Extracorporeal and endoscopic treatments are usually preferred, while open surgery is actually limited to few selected cases. Residual stones or fragments should be treated by chemolysis via ureteral catheter or nephrostomy or administration of citrate salts in order to achieve a stone-free renal unit. Postoperatively, recurrent urinary tract infection should be treated with appropriate antibiotic treatment although long-term antibiotic prophylaxis can cause resistance. Urinary acidification has been proposed for the prophylaxis of infection stones, but long-term acidification is difficult to achieve in urine infected by urease-producing bacteria. Urease inhibitors lead to prevention and/or dissolution of stones and encrustations in patients with infection by urea-splitting bacteria, but their use is limited by their toxicity. The administration of citrate salts involves an increase of the value of nucleation pH (pHn), that is the pH value at which calcium and magnesium phosphate crystallization occurs, in a greater way than the corresponding increase in the urinary pH due to its alkalinizing effect and resulting in a reduction of the risk of struvite crystallization. In conclusion prevention of the recurrence of infection stones can be achieved by an integrated approach tailored on the single patient. Complete clearance of the stone must be achieved by primary surgical procedure and residual fragments should be extensively treated. In the case of persistent infection, conservative measures, such as acidification and urease inhibitors or citrate administration, should be adopted to minimize its effect on urinary saturation with respect to struvite.

A polyherbal formulation attenuates hyperoxaluria-induced oxidative stress and prevents subsequent deposition of calcium oxalate crystals and renal cell injury in rat kidneys.

INTRODUCTION: Cystone is an approved Ayurvedic polyherbal proprietary medicine used in India for various urinary disorders, including urolithiasis. AIM: To evaluate the protective effect of Cystone against hyperoxaluria-induced oxidative stress and calcium oxalate crystal deposition in urolithiasis. METHODS: Ethylene glycol (EG) (0.75%, V/V) in drinking water was given to rats for 28 days to induce urolithiasis with simultaneous treatment of Cystone (500 and 750 mg/kg body weight), and various urinary risk factors of urolithiasis and antioxidant markers were assessed. RESULTS: EG treatment lead to increased urine volume and lowered urinary pH, along with increased urinary excretion of oxalate, calcium and phosphate in untreated animals. These changes caused extensive calcium oxalate crystal deposition, increased lipid peroxidation and decreased activity of antioxidant enzymes (SOD, catalase and GPx) in the kidney of untreated rats. Cystone prevented these hyperoxaluric manifestations and inhibited calcium oxalate crystal deposition in treated rats at both doses. CONCLUSIONS: Cystone therapy provides protection against hyperoxaluria-induced oxidative stress and calcium oxalate crystal deposition by improving renal tissue antioxidant status and diuresis.