Antioxidant activity and Inhibitory effects of Cydonia oblonga Miller. leaves extracts against calcium oxalate stones.

Urinary stone disease is a widespread health problem in both adults and children, and its prevalence has been increasing worldwide. Various plants preparations have already been used since ancient times in order to treat urolithiasis. The aim of this study is to evaluate the antioxidant capacity and litholytic effect on kidney stones of Cydonia oblonga Miller. leaves. The infusion, methanol and acetone extracts were made from Cydonia oblonga Miller. leaf at different concentration. Estimation of mass fractions of total polyphenol, flavonoid, and flavonol contents, as well as the in vitro radical scavenging potential on 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH·) of the investigated extracts was carried out using colorimetric methods. The litholytic property of the extracts was performed by an in-vitro model using experimentally prepared kidney stones- calcium oxalate. As results, the quince leaf extracts revealed stronger antioxidant properties in the DPPH assay, which was proved by the semi-maximal inhibitory concentration values, being about 36.06 ± 3.55, 74.15 ± 6.29, and 142.35 ± 5.09 µg/ml for methanol, acetone and infusion extracts respectively. Furthermore, the tested extracts were found to be more effective in dissolving calcium oxalate stones compared to the control solutions, the mass loss is about 15.13 ± 1.10% with methanol extract, while it is 14.77 ± 1.74% and 11.14 ± 2.86% for acetone and infusion extracts respectively. These findings confirm the quince leaf's richness in phyto-components, offering anti-oxidant property and being able to be used as a remedy for the management of kidney stones by dissolving calcium oxalate stones in the kidneys.

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.

Efficacy of Bisphosphonate for Urolithiasis Complicated by Osteogenesis Imperfecta.

A 44-year-old man with osteogenesis imperfecta presented with left renal colic. Non-contrast computed tomography revealed a stone (10×9 mm) in the left upper ureter. Ureteroscopic lithotripsy was performed twice and stone-free status was achieved. An analysis of the stone revealed a mixed composition including calcium oxalate and calcium phosphate. Postoperatively, we administered bisphosphonates to prevent recurrence of urolithiasis, as 24-hour urine collection revealed marked hypercalciuria. Eighteen months after surgery, the urinary calcium levels had normalized, and there was no recurrence of urolithiasis. Osteogenesis imperfecta can be complicated by urolithiasis, but bisphosphonates may be useful in preventing recurrence of this disease.

Uroliths composed of antiviral compound GS-441524 in 2 cats undergoing treatment for feline infectious peritonitis.

Feline infectious peritonitis (FIP) historically has been a fatal disease in cats. Recent unlicensed use of antiviral medication has been shown to markedly improve survival of this infection. An 8-month-old female spayed domestic short-haired cat undergoing treatment for presumptive FIP with the antiviral nucleoside analog GS-441524 developed acute progressive azotemia. Abdominal ultrasound examination identified multifocal urolithiasis including renal, ureteral, and cystic calculi. Unilateral ureteral obstruction progressed to suspected bilateral ureteral obstruction and subcutaneous ureteral bypass (SUB) was performed along with urolith removal and submission for analysis. A 2-year-old male neutered domestic medium-haired cat undergoing treatment for confirmed FIP with GS-441524 developed dysuria (weak urine stream, urinary incontinence, and difficulty expressing the urinary bladder). This cat also was diagnosed sonographically with multifocal urolithiasis requiring temporary tube cystostomy after cystotomy and urolith removal. In both cases, initial urolith analysis showed unidentified material. Additional testing confirmed the calculi in both cats to be 98% consistent with GS-441524. Additional clinical studies are required to determine best screening practices for cats presented for urolithiasis during treatment with GS-441524.

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.

[Influence of non-drug complex programs on severity of pain syndrome, psychoemotional status and quality of life in patients with urolithiasis before and after percutaneous nephroscopy]. / Osobennosti vliyaniya nemedikamentoznykh kompleksnykh programm na vyrazhennost' bolevogo sindroma, psikhoemotsional'nyi status i kachestvo zhizni patsientov s mochekamennoi bolezn'yu do i posle perkutannoi nefroskopii.

OBJECTIVE: To study the effect of non-drug complex programs including intravenous laser blood irradiation (ILBI) combined with ozone therapy and light therapy on severity of pain syndrome, psychoemotional status and quality of life in patients with urolithiasis before and after percutaneous nephroscopy. MATERIAL AND METHODS: The study included 90 patients with urolithiasis aged 28-62 years (mean 37.6±4.5 years). Patients were divided into 3 groups comparable in age, sex, clinical and functional characteristics: group 1 (n=30) - standard therapy with a course of ILBI combined with ozone therapy (6 procedures) in preoperative period and polarized light therapy and ILBI (6 procedures) in early postoperative period (the next day after surgery); group 2 (n=30) - ILBI combined with ozone therapy in early postoperative period along standard therapy; group 3 (n=30) - standard postoperative therapy (antispasmodics, antibiotic therapy based on bacterial culture of urine, non-steroidal anti-inflammatory drugs). To assess the effectiveness of treatment, we used 11-point numerical rating scale (NRS), 10-point SAM test (well-being, activity and mood) and short version of the SF-12 health questionnaire. RESULTS: Mean NRS score of pain prior to treatment was 5.9±0.8 points. After the course of rehabilitation in the 1st group, there was a significant decrease in intensity of pain (up to NRS score 1.1±0.1, p<0.001). In the 2nd group, analgesic effect was less significant (2.3±0.2 points; p<0.01). In the 3rd group, this value was 3.6±0.2 (p<0.001). The most significant dynamics of all indicators in SAM test was recorded in the 1st group (the indicators reached the values of healthy individuals). In the 2nd group, all indicators were 12.7-17.9% less than in the 1st group. In the 3rd group, the values were 32.4-39.4% less than in the 1st group ( p<0.05). According to the SF-12 questionnaire, 6.7% of patients reported low quality of life after treatment (compared to 83.3 and 53.3% in the 2nd and 3rd groups, respectively), 23.3% of patients reported high quality of life (10% in the 2nd group, no patients in the 3rd group). CONCLUSION: Two courses of non-drug rehabilitation including ILBI and ozone therapy in preoperative period and polarized light with ILBI in early postoperative period after percutaneous nephroscopy contribute to analgesic and psychocorrective effects. This significantly improves the quality of life of patients with urolithiasis before and after intervention.

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.

Antiurolithiatic Potential of Three Sri Lankan Medicinal Plants by the Inhibition of Nucleation, Growth, and Aggregation of Calcium Oxalate Crystals In Vitro.

Background: Deposition and formation of stones in any part of the urinary system is called urolithiasis. CaOx is the predominant component of most stones, and the formation of these stones is a multistep process that includes supersaturation, nucleation, aggregation, growth, and retention. In ayurvedic medicine, medicinal plants are used for the management of kidney stones. The objective of this study was to determine the effect of aqueous, ethanol, and hexane extracts of Drymoglossum piloselloides leaves, Kalanchoe laciniata leaves, and Aegle marmelos flowers against CaOx urolithiasis in vitro. Methods: The crystallization of CaOx monohydrate (COM) and dihydrate (COD) was induced in a synthetic urine system. The nucleation, growth, and aggregation of crystals were measured using spectrophotometric methods. The results were compared against the polyherbal drug, Cystone, under identical concentrations. Crystals generated in the urine were also observed under light microscopy. Statistical differences and percentage inhibitions were calculated using standard formulae and compared. A preliminary phytochemical screening was also performed to detect active phytoconstituents present in the three plants used in the study. Results: The results obtained clearly demonstrated that Kalanchoe laciniata, Aegle marmelos, and Drymoglossum piloselloides have the capacity to inhibit the nucleation, growth, and aggregation of CaOx crystals. Microscopic examination of crystals revealed the presence of more COM than COD crystals but a dose-dependent reduction in crystals was observed in the presence of plant extracts. Hexane, ethanol, and aqueous extracts of all three plants had different capabilities to inhibit nucleation, growth, and aggregation of CaOx crystals but their activities were different at different concentrations. Preliminary phytochemical screening revealed the presence of reducing sugars, proteins, flavonoids, tannins, and polyphenol compound in Kalanchoe laciniata and Drymoglossum piloselloides and reducing sugars, proteins, anthracene glycosides, and saponins in Aegle marmelos. Conclusions: This study provided evidence that Kalanchoe laciniata, Aegle marmelos, and Drymoglossum piloselloides have the potential to be developed as inhibitors of nucleation, growth, and aggregation of CaOx crystals in the treatment of urolithiasis.

Plants Used in Mexican Traditional Medicine for the Management of Urolithiasis: A Review of Preclinical Evidence, Bioactive Compounds, and Molecular Mechanisms.

Urolithiasis (UL) involves the formation of stones in different parts of the urinary tract. UL is a health problem, and its prevalence has increased considerably in developing countries. Several regions use plants in traditional medicine as an alternative in the treatment or prevention of UL. Mexico has known about the role of traditional medicine in the management of urinary stones. Mexican traditional medicine uses plants such as Argemone mexicana L., Berberis trifoliata Hartw. ex Lindl., Costus mexicanus Liebm, Chenopodium album L., Ammi visnaga (L.) Lam., Eysenhardtia polystachya (Ortega) Sarg., Selaginella lepidophylla (Hook. & Grev.) Spring, and Taraxacum officinale L. These plants contain different bioactive compounds, including polyphenols, flavonoids, phytosterols, saponins, furanochromones, alkaloids, and terpenoids, which could be effective in preventing the process of stone formation. Evidence suggests that their beneficial effects might be associated with litholytic, antispasmodic, and diuretic activities, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals. The molecular mechanisms involving these effects could be related to antioxidant, anti-inflammatory, and antimicrobial properties. Thus, the review aims to summarize the preclinical evidence, bioactive compounds, and molecular mechanisms of the plants used in Mexican traditional medicine for the management of UL.

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.

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.

An Unusual Course of a 2,8-Dihydroxyadeninuria Crystalline Nephropathy Secondary to Adenine Phosphoribosyltransferase Deficiency.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare disorder caused by an autosomal recessive genetic disease leading to the deposition of 2,8-dihydroxyadenine (2,8-DHA) in the kidney. The disease remains under-recognized, oftentimes diagnosed in late stages of renal insufficiency or a failed kidney allograft with biopsy-proven disease recurrence. Here, we present the case of a 59-year-old middle eastern male patient diagnosed with 2,8-DHA nephropathy after a very unusual presentation, and we show how the initiation of an appropriate therapy slowed down his evolution toward kidney replacement therapies. His disease was found to be secondary to a specific APRT gene variant c.188G>A p (Gly63Asp) also described in 4 other patients, all from middle eastern origins.

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.

Downregulation of inflammatory mediators by ethanolic extract of Bergenia ligulata (Wall.) in oxalate injured renal epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Indian traditional system of medicine, Bergenia ligulata (Wall.) Engl. has been used for treatment of urolithiasis. Its efficacious nature has led to its incorporation in various commercial herbal formulations such as Cystone and Neeri which are prescribed for kidney related ailments. AIM OF THE STUDY: To assess whether ethanolic extract of B. ligulata can mitigate the cascade of inflammatory responses that cause oxidative stress and ultimately cell death in renal epithelial cells exposed to hyperoxaluric conditions. MATERIAL AND METHODS: Bioactivity guided fractionation using solvents of varying polarities was employed to evaluate the potential of the extracts of B. ligulata to inhibit the crystallization process. Modulation of crystal morphology was visualized through Scanning electron microscopy (SEM) analysis. Cell death was assessed using flow cytometry based assays. Alteration in the inflammatory mediators was evaluated using real time PCR and immunocytochemistry. Phytochemical characterization of the ethanolic extract was carried out using FTIR, LC-MS and GC-MS. RESULTS: Bioactivity guided fractionation for the assessment of antilithiatic activity revealed dose dependent inhibition of nucleation and aggregation process of calcium oxalate crystals in the presence of various extracts, however ethanolic extract showed maximum inhibition and was chosen for further experiments. Studies on renal epithelial NRK-52E cells showed, cytoprotective efficacy of B. ligulata extract against oxalate injury. SEM anaysis further revealed the potential of the extract to modulate the crystal structure and adhesion to renal cell surface. Exposure of the renal cells to the extract led to conversion of the calcium oxalate monohydrate (COM) crystals to the less injurious calcium oxalate dihydrate (COD) form. Expression analysis for oxidative stress and inflammatory biomarkers in NRK-52E cells revealed up-regulation of Mitogen activated protein kinase (MAPK), Osteopontin (OPN) and Nuclear factor- ĸB (NF-ĸB), in response to calcium oxalate insult; which was drastically reduced in the presence of B. ligulata extract. Flow cytometric evaluation pointed to caspase 3 mediated apoptotic cell death in oxalate injured cells, which was attenuated by B. ligulata extract. CONCLUSION: Considering the complex multifactorial etiology of urolithiasis, ethanolic extract from B. ligulata can be a promising option for the management of kidney stones, as it has the potential to limit inflammation and the subsequent cell death.

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.