Systematic review and meta-analysis of the efficacy of clinically tested protectants of cisplatin nephrotoxicity.

INTRODUCTION: Cisplatin is a potent antineoplastic drug that has been widely used to treat a number of solid tumors. However, a high incidence of renal damage observed in patients has led researchers to search for alternate strategies that prevent or at least reduce the cisplatin-induced nephrotoxicity. The objective of the present study was to conduct a systematic review and a subsequent meta-analysis to evaluate and identify compounds with effective antitumor activity and lesser side effects that could provide protection against cisplatin-induced nephrotoxicity. METHODS: The study included all placebo-controlled trials published up to December 2017 that met the inclusion criteria. A total of 22 articles were finally included to extract the following information: number of patients, doses of cisplatin and protectant, qualitative (acute kidney injury incidence) and quantitative (plasma creatinine, blood urea nitrogen, and creatinine clearance) indicators of renal function. The odds ratio or the mean difference (95% confidence interval) of each parameter was calculated for each study and group of studies. RESULTS: The results of this meta-analysis show that there is great variability in the nephroprotective capacity of a variety of products evaluated. Of all the compounds tested, only magnesium sulfate and cystone were found to exert protective effects. However, more studies need to be conducted to confirm these results. CONCLUSIONS: The administration of 1 g of Mg i.v. seems to be the best strategy for the prevention of cisplatin nephrotoxicity.

In Vitro and In Silico Evaluation of Betulin on Calcium Oxalate Crystal Formation.

Objective: The medicinal plant Betula alba has been used for prevention and treatment of kidney stones. Betulin is one of the main phytochemicals of Betula alba. The aim of this study is to investigate the antioxidant and antiurolithiatic activity of betulin in vitro and in silico. For antioxidant activity, 2, 2-diphenyl-1-picrylhydrazyl (DPPH), total reducing capacity, nitric oxide (NO) radical scavenging assay, and superoxide radical scavenging assay were studied. Method: In order to study antiurolithiatic activity, three assays such as crystallization, nucleation, and aggregation of oxalate crystal in urine were performed. In silico experiments were performed by using AutoDock 4.2 tools in order to establish affinity of phytochemicals toward antioxidant enzyme and matrix metalloproteinase (MMP-2 and 9). Results: The results obtained clearly demonstrate the significant scavenging activity of betulin and cystone against DPPH, NO, and superoxide radicals in comparison to standard antioxidant L-ascorbate (L-AA). It has also been observed that betulin has the capacity to inhibit the crystallization, nucleation, and aggregation in comparison to cystone. On the other hand, betulin and L-AA showed strong affinity toward antioxidant enzymes and matrix metalloproteinase as determined by in silico experiments. Conclusions: From this, it may be concluded that the antiurolithiatic activity of betulin is, at least in part, mediated by its antioxidant property.

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®.

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.

Efficacy of Ficus tikoua Bur. extract in ethylene glycol-induced urolithiasis model in SD rats.

The development of new herbal preparations for the treatment of urolithiasis is an urgent task of medical science. Ficus have attracted the attention of pharmacologists due to a wide range of biological properties, including antioxidant, anti-inflammatory, antibacterial and antifungal activity. We studied the effectiveness of Ficus tikoua Bur. in SD rats in which urolithiasis was induced by 6 weeks of oral administration of ethylene glycol 0.5% ad libitum instead of drinking water. Administration of the extract of Ficus tikoua Bur., as well as comparative drug Cystone® after modeling of urolithiasis lead to the restoration of diuresis and the concentration of inorganic phosphates starting from the 6th week of the experiment. The use of the Ficus tikoua Bur. extract for 6 weeks, both during the modeling of urolithiasis and during the recovery period, led to the restoration of the percentage of lymphocytes in the blood, content of sodium, chlorine and inorganic phosphates in the blood to the control level. Thus, the extract of Ficus tikoua Bur. seems to be a promising drug for effective treatment of the initial stages of the development of urolithiasis.

Methanolic extract of Cucumis melo attenuates ethylene glycol-induced nephrolithiasis in Wistar rats.

Evaluation of the effects of methanolic extract of Cucumis melo in ethylene glycol-induced nephrolithiasis on Wistar rats. 0.75% solution of ethylene glycol (EG) in payable water was given to produce nephrolithiasis on Wistar rats. The action of oral intake of methanolic extract of Cucumis melo seed in nephrolithiasis is studied and is matched with the action of oral intake of Cystone (standard) on Wistar rats. EG resulted in hyperoxaluria and deposition of calcium oxalate as well as raised urinary excretion of oxalate and calcium. Supplementation with methanolic extract of Cucumis melo seed decreased the increased renal oxalate, indicating a regulatory effect on oxalate formation endogenously. The outcomes stipulate that the seed of Cucumis melo is endowed with antinephrolithiatic action.

Anti-urolithiatic activity of Bryophyllum pinnatum Lam. hydroalcoholic extract in sodium oxalate-induced urolithiasis in rats.

BACKGROUND AND AIM: Despite advances in modern medicine, the development and growth of calculi continues to be a source of concern for mankind, as there is no effective treatment for kidney stones. In the present study we investigated antiurolithiatic activity of Bryophyllum pinnatum Lam against sodium oxalate (NaOx) induced urolithiasis in rats. EXPERIMENTAL PROCEDURE: In rats with renal calculi caused by sodium oxalate (NaOx, 70 mg/kg, i.p.); the antiurolithiatic action of Bryophyllum pinnatum hydroalcoholic extract (BPHE) was studied. BPHE was given every day orally at doses of 50, 200 mg/kg for 14 days to rats to examine activity against sodium oxalate (NaOx) mediated urolithiasis, with Cystone (500 mg/kg, p.o.) as a reference standard. The effect of the extract on urine oxalate, creatinine and phosphate retention and excretion in the kidney, as well as serum and biochemical analysis of kidney homogenate and histopathological examinations were studied. RESULTS AND CONCLUSION: Oral administration of BPHE at doses of 50,100, and 200 mg/kg to rats with sodium oxalate-mediated renal calculi showed dose-dependent substantial (P<0.05) antiurolithiatic potential, with notable reversal of NaOx-induced ion excretion and urinary CaOx concentration. These findings justify the traditional use of Bryophyllum pinnatum hydroalcoholic extract (BPHE) in the treatment of renal calculi.

Pharmacological studies on the efficacy of a thymoquinone-containing novel polyherbal formulation against cisplatin-induced hepatorenal toxicity in rats.

The aim of this study was to investigate the protective effect of a novel polyherbal formulation against cisplatin-induced hepatorenal toxicity in six groups of rats. Group I: Normal control; Group II: cisplatin (5 mg/kg i.p.); Group III: cisplatin (5 mg/kg i.p.) + cystone (750 mg/kg p.o.); Group IV: cisplatin + Costus speciosus, Fumaria indica, Cichorium intybus, and thymoquinone (CFCT) (25 mg/kg p.o.); Group V: cisplatin + CFCT-50; Group VI: cisplatin + CFCT-100. The rats were treated for 4 weeks. Serum and tissue biochemical parameters were assessed. The results showed that aspartate aminotransferase (131.8 IU/L), alanine aminotransferase (66.75 IU/L), alkaline phosphatase (168.67 IU/L), cholesterol (135.15 IU/L), serum urea (56.76 mg/dl), blood urea nitrogen (47.52 mg/dl), and creatinine (3.11 mg/dl) were significantly elevated (p < .001), while total protein (79.02 g/L) was reduced (p < .001) in the cisplatin group. These results were complemented by the outcomes of antioxidant parameters. Finally, CFCT formulation significantly ameliorated cisplatin toxicity. PRACTICAL APPLICATIONS: In this study, it is revealed that the administration of novel polyherbal formulation (Costus speciosus, Fumaria indica, Cichorium intybus, and thymoquinone [CFCT]) containing Costus speciosus, Fumaria indica, Cichorium intybus, and thymoquinone ameliorated cisplatin-induced hepatorenal injury in rats. The ameliorative effects against cisplatin toxicity could be via contributing to the antioxidant defense system, by scavenging free radicals and reducing oxidative stress and inflammatory responses. This study aimed at being beneficial to cancer's patients, as they are compelled to take cisplatin, and ultimately suffer from the consequences of irreversible nephrotoxic damage. Furthermore, CFCT formulation could be considered as a dietary supplement for the reduction of cisplatin-induced hepatorenal toxicity in cancer patients on cisplatin treatment. However, further clinical study is necessary.

Evaluation of the Protective Effect of Cystone Against Cisplatin-induced Nephrotoxicity in Patients with Cancer: A Pilot Study.

INTRODUCTION: Cisplatin is a widely used anti-cancer drug that is commonly administered for the treatment of various cancers. However, nephrotoxicity is the most important side effect of this drug which limits its use. This study aimed to investigate the protective effect of Cystone against nephrotoxicity induced by Cisplatin in patients with cancer. METHODS: This pilot clinical trial study was conducted on 43 cancer patients treated with Cisplatin (75 mg/m2 for a period of six months). The subjects were divided into treatment group (receiving Cystone, two per 8 hours; n = 21) and control group (n = 22). The two groups were compared with each other in terms of demographic and laboratory variables. RESULTS: In the intervention group receiving Cystone, serum creatinine-based GFR level (P = 0.453) and 24-hour urine creatinine-based GFR level (P = 0.397) did not change significantly during the studied period, but in the control group, serum creatinine-based GFR level (P = 0.013) and 24-hour urine creatinine-based GFR level (P = 0.016) significantly changed. Serum creatinine-based GFR level increased by 2.3 units in the intervention group and 10.5 units in the control group (P = 0.005) in the six months of the study. At the end of the sixth month, 24-hour urine creatinine-based GFR level increased by 2.2 units in the intervention group and 0.8 unit in the control group (P = 0.008). CONCLUSIONS: The use of Cystone resulted in more stable kidney function indices in the intervention group, as compared with the control group. Therefore, Cystone seems to have a protective effect against nephrotoxicity induced by Cisplatin in cancer patients.

Effect of Piper cubeba L. fruit on ethylene glycol and ammonium chloride induced urolithiasis in male Sprague Dawley rats.

BACKGROUND: To investigate the antilithiatic effect of hydroalcoholic extract of Kabab Chini (Piper cubeba L.) fruit in male Sprague Dawley rats. METHODS: Rats were divided into six groups of six each. Group I received regular rat food and drinking water ad libitum. Groups II to VI were administered with ethylene glycol (EG) 0.75% (V/V) and ammonium chloride (AC) 1% (W/V) in drinking water for 7 days to induce urolithiasis. From 8th day Group I received 1 mL of 5% gum acacia. Group IV was treated with Cystone; V and VI groups with the hydro-alcoholic extract of Piper cubeba L. Treatment was continued for further 14 days, thereafter animals sacrificed. While Group II animals were sacrificed just after 7 days treatment with EG and AC. Group III was left untreated until 14 days and sacrificed on 22nd day. Crystalluria was analyzed on 8th and 22nd day while, urinary calcium, phosphorus, creatinine, sodium and magnesium on 22nd day. Biochemistry and histopathological studies of kidney were also carried out. RESULTS: Test groups showed significant reduction (p < 0.001) of crystals in urine. Serum creatinine and urea (p < 0.01) were also decreased significantly. Urine analysis showed significant increase in magnesium while calcium, sodium, chloride and phosphorus significantly decreased along with histopathological improvement in kidney tissue in treated groups. CONCLUSION: From the above results it can be concluded that hydroalcoholic extract of P. cubeba L. fruit has significant inhibitory effect in calcium oxalate urolithiasis.

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

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

Effect of hydro-alcoholic extract of Vernonia cinerea Less. against ethylene glycol-induced urolithiasis in rats.

OBJECTIVE: Aim of this study is to evaluate antiurolithiatic potential of whole plant hydro-alcoholic (30:70) extract of Vernonia cinerea Less. in accordance to its claims made in ancient literature and also being one of the ingredients of cystone, a marketed formulation widely used in the management of urolithiasis. MATERIALS AND METHODS: To induce urolithiasis, 0.75% v/v ethylene glycol was administered orally for 14 days. The curative dose of 400 mg/kg b.w. and preventive doses of 100, 200, and 400 mg/kg b.w. were administered from 15th to 28th and 1st to 28 days, respectively. Cystone 750 mg/kg b.w. was selected as the reference standard for both curative and preventive doses. On 28th day, urinate of 24 h was collected and subjected for estimation of calcium, oxalate, and phosphates. Serum biochemical and kidney homogenate analysis was done for determination of renal oxalate contents. RESULTS: The diseased Group II showed marked increase (P < 0.001 vs. normal Group I) in levels of urine calcium, oxalate, and phosphate. Serum creatinine, urea, and uric acid levels were also increased. Histopathological studies of kidney sections revealed significant changes. Treatment with hydro-alcoholic extract of V. cinerea showed significant (P < 0.01 vs. calculi-induced Group II) dose-dependent activity. A progressive increase in urine output, body weight, and decline in concentrations of stone-forming components such as calcium, oxalates, and phosphates was observed. CONCLUSION: It can be inferred that V. cinerea Less. is effective in ethylene glycol-induced urolithiasis and may have a potential in preventing and curing urolithiasis.

Protective Effect of Propolis in Proteinuria, Crystaluria, Nephrotoxicity and Hepatotoxicity Induced by Ethylene Glycol Ingestion.

BACKGROUND AND AIMS: Propolis is a natural honeybee product with wide biological activities and potential therapeutic properties. The aim of the study is to evaluate the protective effect of propolis extract on nephrotoxicity and hepatotoxicity induced by ethylene glycol in rats. METHODS: Five groups of rats were used. Group 1 received drinking water, group 2 received 0.75% ethylene-glycol in drinking water, group 3 received 0.75% ethylene-glycol in drinking water along with cystone 500 mg/kg/body weight (bw) daily, group 4 received 0.75% ethylene-glycol in drinking water along with propolis extract at a dose of 100 mg/kg/bw daily, and group 5 received 0.75% ethylene-glycol in drinking water along with propolis extract at a dose of 250 mg/kg/bw daily. The treatment continued for a total of 30 d. Urinalyses for pH, crystals, protein, creatinine, uric acid and electrolytes, and renal and liver function tests were performed. RESULTS: Ethylene-glycol increased urinary pH, urinary volume, and urinary calcium, phosphorus, uric acid and protein excretion. It decreased creatinine clearance and magnesium and caused crystaluria. Treatment with propolis extract or cystone normalized the level of magnesium, creatinine, sodium, potassium and chloride. Propolis is more potent than cystone. Propolis extract alleviates urinary protein excretion and ameliorates the deterioration of liver and kidney function caused by ethylene glycol. CONCLUSIONS: Propolis extract has a potential protective effect against ethylene glycol induced hepatotoxicity and nephrotoxicity and has a potential to treat and prevent urinary calculus, crystaluria and proteinuria.

A novel polyherbal formulation containing thymoquinone attenuates carbon tetrachloride-induced hepatorenal injury in a rat model

Objective: To evaluate a novel polyherbal formulation (BSVT) containing the standardized extracts from the leaves of Boerhavia diffusa, Solidago virgaurea, Vitex negundo, and thymoquinone in CCl

Anti-urolithiatic activity of standardized extract of Biophytum sensitivum against zinc disc implantation induced urolithiasis in rats.

Biophytum sensitivum (L.) DC (family: Oxalidaceae) has been used in the Indian indigenous system of medicine, Ayurveda, for the treatment of various health aliments including renal calculi. The present study was undertaken to investigate the anti-urolithiatic activity of standardized methanolic extract of whole plant of B. sensitivum (MBS) in rats. Urolithiasis was induced by surgical implantations of zinc disc in the urinary bladders of rats. Upon postsurgical recovery, different doses of MBS (viz., 100, 200, and 400 mg/kg body weight) were administered to zinc disc-implanted rats for the period of 7 days by the oral route. Anti-urolithiatic activity was evaluated by measuring various dimensions of stones and estimating levels of various biomarkers in serum and urine samples. A significant decrease in urinary output was observed in the disc-implanted animals, which was prevented by the MBS treatment. Supplementation with MBS caused significant improvement in glomerular filtration rate and protein excretion. The elevated levels of serum creatinine, uric acid, and blood urea nitrogen were also prevented by the MBS treatment. The MBS treatment showed reduced formation of deposition around the implanted zinc disc. The higher dose of MBS (400 mg/kg) found more effective. These results indicate that the administration of MBS significantly prevents the growth of urinary stones. The possible mechanism underlying this effect is mediated collectively through diuretic, antioxidant and anti-inflammatory effects of the plant. The results concluded that the methanolic extract of whole plant of B. sensitivum possessed significant anti-urolithiatic activity.

A novel polyherbal formulation containing thymoquinone attenuates carbon tetrachloride-induced hepatorenal injury in a rat model

Objective: To evaluate a novel polyherbal formulation (BSVT) containing the standardized extracts from the leaves of Boerhavia diffusa, Solidago virgaurea, Vitex negundo, and thymoquinone in CCl4 induced hepatorenal toxicity in rats. Methods: A total of 36 rats were divided into six groups including normal control, CCl4 (2 mL/kg, i.p.), CCl4 (2 mL/kg, i.p.) + Cystone? (750 mg/kg p.o.), CCl4 (2 mL/kg, i.p.) + BSVT (25 mg/kg, p.o.), CCl4 (2 mL/kg, i.p.) + BSVT (50 mg/kg, p.o.), and CCl4 (2 mL/kg, i.p.) + BSVT (100 mg/kg, p.o.). All treatments were given for four weeks. Serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, total protein, serum urea, blood urea nitrogen and creatinine were assessed. Superoxide dismutase, malondialdehyde, and glutathione peroxidase were evaluated in tissue homogenate. The histopathological study of liver and kidney tissues was also done. Results: Aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, serum urea, blood urea nitrogen and creatinine were significantly elevated (P<0.001) while total protein was considerably reduced in the CCl4 group as compared to the normal control (P<0.001), which indicated hepatorenal toxicity. In addition, superoxide dismutase and glutathione peroxidase activities were significantly decreased (P<0.001) while malondialdehyde levels were increased markedly (P<0.001). Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner. Conclusions: BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner. Furthermore, clinical studies are required to confirm its efficacy.

Effect of Lagenaria siceraria fruit powder on sodium oxalate induced urolithiasis in Wistar rats.

BACKGROUND: In spite of advances in the present practice of medicine, the formation and growth of calculi continues to trouble mankind, as there is no satisfactory drug to treat kidney stones. In India, many indigenous drugs are in use for the treatment of urinary calculus disease. OBJECTIVE: The present study was intended to determine anti-urolithiatic effect of Lagenaria siceraria fruit powder (LSFP) against sodium oxalate (NaOx) induced urolithiasis in rats. MATERIALS AND METHODS: Animals were grouped as Vehicle Group (received vehicle gum acacia 2% w/v 1 mL/kg/p.o.), NaOx Group(Sodium oxalate 70 mg/kg,i.p.), LSFP Group (500 mg/kg, p.o. LSFP suspended in gum acacia 2% + Sodium oxalate 70 mg/kg), Cystone Group (500 mg/kg, p.o. Cystone suspended in gum acacia 2% + Sodium oxalate 70 mg/kg). RESULT: The increased severity of microscopic calcium oxalate (CaOx) crystals deposition along with increased concentration in the kidney was seen after 7 days of NaOx (70 mg/kg, i.p.) pre-treatment. LSFP (500 mg/kg, p.o.) and standard marketed formulation Cystone (500 mg/kg, p.o.) caused a significant reversal of NaOx-induced changes in ion excretion and urinary CaOx concentration in 7 days treatment. CONCLUSION: From the results, it was concluded that LSFP showed beneficial effect against urolithiasis by decreasing CaOx excretion and preventing crystal deposition in the kidney tubules.