Targeting urinary calcium oxalate crystallization with inulin-type AOFOS from Aspidopterys obcordata Hemsl. for the management of rat urolithiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate crystals play a key role in the development and recurrence of kidney stones (also known as urolithiasis); thus, inhibiting the formation of these crystals is a central focus of urolithiasis prevention and treatment. Previously, we reported the noteworthy in vitro inhibitory effects of Aspidopterys obcordata fructo oligosaccharide (AOFOS), an active polysaccharide of the traditional Dai medicine Aspidopterys obcordata Hemsl. (commonly known as Hei Gai Guan), on the growth of calcium oxalate crystals. AIM OF THE STUDY: To investigated the effectiveness and mechanism of AOFOS in treating kidney stones. MATERIALS AND METHODS: A kidney stones rats model was developed, followed by examining AOFOS transport dynamics and effectiveness in live rats. Additionally, a correlation between the polysaccharide and calcium oxalate crystals was studied by combining crystallization experiments with density functional theory calculations. RESULTS: The results showed that the polysaccharide was transported to the urinary system. Furthermore, their accumulation was inhibited by controlling their crystallization and modulating calcium ion and oxalate properties in the urine. Consequently, this approach helped effectively prevent kidney stone formation in the rats. CONCLUSIONS: The present study emphasized the role of the polysaccharide AOFOS in modulating crystal properties and controlling crystal growth, providing valuable insights into their potential therapeutic use in managing kidney stone formation.

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.

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.

The anti-urolithiasis activity and safety of strangury-relieving herbs: A comparative study based on fruit fly kidney stone model.

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithiasis is one of the oldest and most widespread urological diseases suffered globally. In the long history of Traditional Chinese Medicine, there're numerous herbs documented with strangury-relieving properties playing crucial roles in treating various urological disorders, including dysuria, hematuria, and renal colic, etc., which may be caused by urolithiasis. Exploring these herbs may reveal safer, more effective, and cost-efficient drugs and therapies for urolithiasis. AIM OF THE STUDY: This study aims to assess the anti-urolithiasis efficacy and safety of 46 Chinese traditional and folk herbal drugs using the fruit fly (Drosophila melanogaster) kidney stone model, in order to identify the most valuable ethnomedicinal materials. MATERIALS AND METHODS: Water extract and 50% ethanol extract of each herb were prepared respectively. 0.2% (w/w) sodium oxalate was chosen as appropriate lithogenic agent through fruit fly life span study. Male fruit-flies within three days of emergence were aged for an additional three days, then were randomly divided into experimental groups, model group and control groups (n = 20). The flies in blank control group, model group and positive control group were fed with standard food, standard food containing 0.2% sodium oxalate, standard food containing 0.2% sodium oxalate and 3% (w/w) Garcinia cambogia extract, respectively. Meanwhile, flies in the experimental groups were raised on standard food containing 0.2% sodium oxalate and 3% (w/w) herbal extract. The anti-urolithiasis capability of the extracts was evaluated using stone area ratio (the stone area divided by the area of the Malpighian tubule) and stone-clearing rate. Additionally, the 7-day mortality rate was employed as an indicator of safety. RESULTS: Out of the 46 herbs, 24 exhibited significant anti-urolithiasis effects in their water extracts. Among them, Herba Nephrolepidis, Herba Humuli, Herba Desmodii Styracifolii, Cortex Plumeriae Rubrae, and Herba Mimosae Pudicae showed us a low 7-day mortality rate of fruit-flies as well. However, only a limited number of herbal extracts (8 out of 46) showed obvious anti-urolithiasis activity in their 50% ethanol extracts. CONCLUSION: Highly potential anti-urolithiasis candidates were discovered from strangury-relieving herbs recorded in classical Traditional Chinese Medicine works, highlighting the significant value of traditional and folk ethnopharmacological knowledge.

Naringen's Effects on Diuresis and Prevention of Urolithiasis in Hypertensive Rats.

This research demonstrates the diuretic effect of naringenin, a flavanone aglycone found in citrus, on spontaneously hypertensive female and male rats (SHR). The data reinforces existing literature findings that male SHR exhibits higher systolic blood pressure than age-matched females. Urine volume assessed over 8 hours was lower when obtained from SHR males than females. When these animals were orally treated with different doses of naringenin (0.1-1 mg/kg), this increased urinary volume in both genders at the highest dose tested. In contrast, the lowest dose promoted a significant natriuretic effect. The other electrolytes analyzed in urine were not significantly altered, except potassium excretion, which was shown to be increased in the urine of SHR males. Furthermore, naringenin showed promise in reducing calcium oxalate (CaOx) crystal formation in an in vitro model, presenting potential advantages in lithiasis prevention.

Clinical patterns and implications of prescription opioid use in a pediatric population for the management of urolithiasis in the emergency room.

Extrapolations from the adult population have suggested that opioids should be avoided in the management of pediatric urolithiasis, but the literature is sparse with regards to actual practice patterns and the downstream implications. We sought to investigate the rate of oral opioid administration for children presenting to the emergency room (ER) with urolithiasis and to identify associations between opioid administration and return visits and persistent opioid use. The TriNetX Research and Diamond Networks were used for retrospective exploratory and validation analyses, respectively. Patients <18 years presenting to the emergency room with urolithiasis were stratified by the receipt of oral opioids. Propensity score matching was performed in a 1:1 fashion. Incident cases of opioid administration and risk ratios (RRs) for a return ER visit within 14 days and the presence of an opioid prescription at 6 to 12 months were calculated. Of the 4672 patients in the exploratory cohort, 11.9% were prescribed oral opioids. Matching yielded a total of 1084 patients. Opioids at the index visit were associated with an increased risk of return visits (RR 1.51, 95% CI 1.04-2.20, P = 0.03) and persistent opioid use (RR 4.00, 95% CI 2.20-7.26, P < 0.001). The validation cohort included 6524 patients, of whom 5.7% were prescribed oral opioids. Matching yielded a total of 722 patients and demonstrated that opioids were associated with an increased risk of return visits (RR 1.50, 95% CI 1.04-2.16, P = 0.03) but not persistent opioid use (RR 1.70, 95% CI 0.79-3.67, P = 0.17). We find that the opioid administration rate for pediatric urolithiasis appears reassuringly low and that opioids are associated with a greater risk of return visits and persistent use.

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.

[Prevention of urolithiasis using febuxostat in patients with metabolic syndrome].

INTRODUCTION: Urolithiasis is a chronic highly recurrent disease. The development of new methods of its pathogenetic treatment and prevention is a priority task of practical urology. AIM: To evaluate the clinical efficiency and safety of Febuxostat-SZ and to develop the rec-ommendations for its use in patients with uric acid stones. MATERIALS AND METHODS: The analysis of 525 patients with urolithiasis was carried out. On the basis of a comprehensive examination, they were divided into two groups: in the group 1, pa-tients (n=231) had urolithiasis and metabolic syndrome, while in the group 2 (n=294), only urolithia-sis was diagnosed without metabolic syndrome. In both groups, depending on the stone composi-tion, in addition to general measures, specific stone prevention was carried out, which included die-tary regimen and drug therapy. RESULTS: Uric acid excretion after 6 months of therapy in patients with urolithiasis and meta-bolic syndrome decreased from 9.8+/-1.8 to 3.9+/-1.1 mmol/l, urinary excretion of citrates and urine acidity increased from 0.8 +/-0.6 to 2.5+/-0.8 mmol/l and from 5.4+/-0.5 to 6.3+/-0.5, respectively, while serum uric acid level decreased from 451.4+/-15.1 up to 385.2+/-16.2 mmol/l. In the group of patients who, in addition to prescribing stone prevention, underwent correction of the metabolic syndrome, uric acid excretion after 3 months decreased by half: from 9.7+/-1.9 to 5.0+/-1.2 mmol/l, urine pH and citrate excretion increased from 5.4+/-0.4 to 6.3+/-0.5 and from 0.8+/-0.5 to 2.3+/-1.0 mmol/l, respective-ly, while serum uric acid level decreased from 459.5+/-17.7 to 370.9+/-15.1 mmol/l after 6 months of treatment. CONCLUSION: The use of Febuxostat-SZ in the complex therapy of urinary stone disease showed high efficiency in normalizing urine acidity, the level of daily excretion and serum uric acid level, as well as satisfactory tolerability and a minimal profile of side effects.

Dietary supplements and medicinal plants in urolithiasis: diet, prevention, and cure.

BACKGROUND: Urolithiasis has been a major health concern for centuries, primarily owing to the limited treatment options in the physician's armamentarium. However, various studies have underscored a lesser incidence of urolithiasis in cohorts predominantly consuming fruits and vegetables. This article aims to review various dietary plants, medicinal herbs and phytochemicals in the prevention and management of urolithiasis. METHODS: To provide context and evidence, relevant publications were identified on Google Scholar, PubMed and Science-Direct using keywords such as urolithiasis, nephrolithiasis, urolithiasis, renal stones, phytochemicals and dietary plants. RESULTS: Growing bodies of evidence suggest the incorporation of plant-based foods, medicinal and herbal supplements, and crude drugs containing phytochemicals into the staple diet of people. The anti-urolithiatic activity of these plant bioactives can be attributed to their antioxidant, antispasmodic, diuretic, and inhibitory effect on the crystallization, nucleation and crystal aggregation effects. These mechanisms would help alleviate the events and symptoms that aid in the development and progression of renal calculi. In addition, it will also avoid the exacerbation of secondary disorders like inflammation and injury, which can initiate a vicious circle in turn worsening the disease progression. CONCLUSION: In conclusion, the results presented in the review demonstrate the promising role of various dietary plants, medicinal and herbal supplements, and phytochemicals in preventing and managing the precipitation of uroliths. However, more conclusive and cogent evidence from preclinical and clinical studies is required to substantiate their safety, efficacy and toxicity profiles in humans.

Potential for Urolithiasis-related Research Using the Novel Medicare-Litholink Database.

INTRODUCTION: To overcome the data availability hurdle of observational studies on urolithiasis, we linked claims data with 24-hour urine results from a large cohort of adults with urolithiasis. This database contains the sample size, clinical granularity, and long-term follow-up needed to study urolithiasis on a broad level. METHODS: We identified adults enrolled in Medicare with urolithiasis who had a 24-hour urine collection processed by Litholink (2011 to 2016). We created a linkage of their collections results and paid Medicare claims. We characterized them across a variety of sociodemographic and clinical factors. We measured frequencies of prescription fills for medications used to prevent stone recurrence, as well as frequencies of symptomatic stone events, among these patients. RESULTS: In total, there were 11,460 patients who performed 18,922 urine collections in the Medicare-Litholink cohort. The majority were male (57%), White (93.2%), and lived in a metropolitan county (51.5%). Results from their initial urine collections revealed abnormal pH to be the most common abnormality (77.2%), followed by low volume (63.8%), hypocitraturia (45.6%), hyperoxaluria (31.1%), hypercalciuria (28.4%), and hyperuricosuria (11.8%). Seventeen percent had prescription fills for alkali monotherapy, and 7.6% had prescription fills for thiazide diuretic monotherapy. Symptomatic stone events occurred in 23.1% at 2 years of follow-up. CONCLUSIONS: We successfully linked Medicare claims with results from 24-hour urine collections performed by adults that were processed by Litholink. The resulting database is a unique resource for future studies on the clinical effectiveness of stone prevention strategies and urolithiasis more broadly.

d,l-Methionine in combination with amoxicillin-clavulanic acid successfully dissolves spontaneously occurring infection-induced struvite urocystoliths in dogs: a pilot study.

OBJECTIVE: To determine the efficacy and safety of a urinary acidifier (d,l-methionine [Methio-Form]) and an antimicrobial agent (amoxicillin-clavulanic acid [Clavamox]) without changing diet for dissolving infection-induced struvite urocystoliths in dogs. ANIMALS: 14 dogs were recruited for this prospective study; 11 completed it and 3 dogs withdrew due to inability of the owners to administer the treatment (n = 2) or refusal of treatment by the dog (1). PROCEDURES: All dogs were administered d,l-methionine (approx initial dose of 75 mg/kg, PO, q 12 h) and amoxicillin-clavulanic acid (22 mg/kg, PO, q 12 h) based on urine culture and sensitivity. Urine pH, urinalysis, urine culture, venous blood gas and serum biochemical analysis, and lateral survey abdominal radiographic images were evaluated initially and every 4 weeks until urolith dissolution (success) or lack of change in size and/or shape of urocystoliths on 2 consecutive reevaluation points (failure) occurred. RESULTS: Uroliths dissolved in 8 of 11 dogs in a median of 2 months (range, 1 to 4 months) with a final effective dosage of d,l-methionine of approximately 100 mg/kg, PO, every 12 hours. In 3 dogs, uroliths failed to dissolve and were removed surgically; they contained variable amounts of calcium oxalate. No adverse events occurred. CLINICAL RELEVANCE: Infection-induced struvite urolithiasis is 1 of the 2 most common minerals occurring in canine uroliths. Results of this study supported the use of d,l-methionine and amoxicillin-clavulanic acid without changing diet for dissolution of infection-induced struvite urocystoliths in dogs.

Dietary management of hypocitraturia in children with urolithiasis: results from a systematic review.

PURPOSE: Hypocitraturia is a low urinary excretion of citrate and a well-known risk factor for kidney stone development in children. This systematic review aimed to evaluate the dietary management of hypocitraturia in children with urolithiasis. METHODS: Literature search was performed on 30th September 2022 using Embase, PubMed, and Cochrane Central Controlled Register of Trials. Studies were included if children with stones and hypocitraturia were managed with diet supplements. RESULTS: Six papers were included. Four studies evaluated the role of oral potassium citrate associated with high fluid intake on stone resolution and recurrence. Two studies assessed the impact of oral potassium citrate on long-term stone recurrence after percutaneous nephrolithotomy and shock wave lithotripsy. All studies demonstrated that the association of potassium citrate and high fluid intake was well tolerated with no side effects and restored normal urine citrate excretion, allowed a reduction in stone size, and, following definitive treatments, was associated with a lower rate of stone regrowth and recurrence compared with controls. These effects were demonstrated across all pediatric ages. CONCLUSIONS: Our review infers that oral potassium citrate and high fluid assumption are safe and effective in restoring urine citrate excretion, treating and preventing stone recurrence with no serious adverse events, and should probably be the first-line treatment of pediatric patients with asymptomatic stones and hypocitraturia.

Himalayan Citrus jambhiri juice reduced renal crystallization in nephrolithiasis by possible inhibition of glycolate oxidase and matrix metalloproteinases.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrus fruits are a very rich source of electrolytes and citric acid. They have been used traditionally for treating urinary ailments and renal stones. Citrus jambhiri is indigenously used as a diuretic. AIM OF THE STUDY: Present study aimed at establishing the antiurolithiatic potential of the juice of Citrus jambhiri fruits along with the elucidation of the mechanism involved in the urolithiasis disease defying activity. METHODS: The antiurolithiatic activity was established by means of nucleation, growth and aggregation assay in the in vitro settings and by means of ethylene glycol mediated calcium oxalate urolithiasis in the male Wistar rats. Docking studies were performed in an attempt to determine the mechanism of the antiurolithiatic action. RESULTS: Present study revealed the role of C. jambhiri fruit juice in reducing nucleation, growth and aggregation of calcium oxalate crystals by possible reduction in the urinary supersaturation relative to calcium oxalate and raising the zeta potential of the calcium oxalate crystals. C. jambhiri fruit juice treatment in experimental rats produced significant amelioration of hypercalciuria, hyperoxaluria, hyperphosphaturia, hyperproteinuria, hyperuricosuria, hypocitraturia and hypomagnesiuria and ion activity product of calcium oxalate. It exhibited nephroprotection against calcium oxalate crystals induced renal tubular dilation and renal tissue deterioration. Docking studies further revealed high binding potential of the phytoconstituents of C. jambhiri viz. narirutin, neohesperidin, hesperidin, rutin and citric acid with glycolate oxidase and matrix metalloproteinase-9. CONCLUSION: C. jambhiri fruit juice possesses excellent antiurolithiatic activity. The study reveals antiurolithiatic mechanism that involves restoration of equilibrium between the promoters and inhibitors of stone formation; and inhibition of matrix metalloproteinases and glycolate oxidase.

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.

Synthesize and characterization of CaOx crystals against various citrus waste peel extracts: an in vitro study.

Citrus fruits have been consumed by world's population for several centuries. Since it's an edible source possesses various uses in treating many diseases. Among various diseases urolithiasis is one of the major issues globally demands in painless surgical treatment. Calcium Oxalate (CaOx) is found to be the most prevailing constituent of renal calculus in humans which tends to be the categories of the urolithiasis. Citric acid is commonly used in treating to dissolve them in medications. Citrate compound has the ability to bind with calcium stones to relieve oxalates in urine. The objective of the present study is to assess the efficacy of citrate compounds from waste citrate peels describing the inhibition of calcium oxalate (CaOx) crystals. Multistep extraction procedures were performed for the selected citrus peels of Citrus limon, Citrus limetta and Citrus sinensis using different solvents (hexane, aqueous and ethanol) and were tested for its inhibitory actions with different parameters against the synthesized CaOx crystals. The synthetic CaOx crystals were characterized by Microscopy, FTIR, SEM, XRD, and TGA. The structural change in the crystal was observed for inhibition at various stages like nucleation, growth and aggregation when treated with the ethanol extracts of citrus peels. Thus the present investigation concludes that the ethanol extracts of C. sinensis peels highly inhibits at a concentration of 1000 (µg/mL) in 60 min when compared to other solvents. This research would give additional information in preparation of drugs against CaOx urolithiasis in future pharmaceutical development processes.

The effects of Cynodon dactylon (Poaceae family) and Dolichos biflorus (Fabaceae family) extracts on decreasing size and excretion of kidney and urinary tract stones: a randomized, double-blind controlled trial.

OBJECTIVES: Given high and growing prevalence rate of urolithiasis in most societies as well as the problems caused by this issue, it is necessary to apply more cost-effective and safer therapeutic methods, which are accessible for all the individuals worldwide. Therefore, this study aimed to investigate efficacy of herbal medicines named Cynodon dactylon and Dolichos biflorus on solving and excretion of renal and urinary tract stones in patients with urolithiasis. METHODS: This study included 96 patients with urolithiasis who were randomly allocated into three groups. The first group received the extract of D. biflorus seeds (1,600 mg), the second group received extract of C. dactylon rhizome (1,600 mg) and the third group received placebo for 21 days. In this study, we used an hydroalcoholic extract of D. biflorus and C. dactylon prepared by Soxhlet method. For each patient, the size of the stones, the amount of calcium in the urine, the number of stones excreted and their chemical substance type were measured. RESULTS: In this study, changes were observed at the significance level in the interventions groups of 1 and 2, and the placebo group in the left kidney, so that changes in size of the stone in left kidney as intergroup were significantly different in these three groups (p=0.02). The mean of changes in stone size in left kidney in the group C. dactylon was 3.78 ± 7.1 and in the group D. biflorus, it was 0.27 ± 0.6. CONCLUSIONS: A significant difference in the results of this study show that C. dactylon rhizome and D. biflorus seed extracts are able to decrease the size of the stone and can be effective on kidney stones excretion.

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.