Antioxidant and Polyphenol-Rich Ethanolic Extract of Rubia tinctorum L. Prevents Urolithiasis in an Ethylene Glycol Experimental Model in Rats.

Treatment of kidney stones is based on symptomatic medications which are associated with side effects such as gastrointestinal symptoms (e.g., nausea, vomiting) and hepatotoxicity. The search for effective plant extracts without the above side effects has demonstrated the involvement of antioxidants in the treatment of kidney stones. A local survey in Morocco has previously revealed the frequent use of Rubia tinctorum L. (RT) for the treatment of kidney stones. In this study, we first explored whether RT ethanolic (E-RT) and ethyl acetate (EA-RT) extracts of Rubia tinctorum L. could prevent the occurrence of urolithiasis in an experimental 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC)-induced rat model. Secondly, we determined the potential antioxidant potency as well as the polyphenol composition of these extracts. An EG/AC regimen for 10 days induced the formation of bipyramid-shaped calcium oxalate crystals in the urine. Concomitantly, serum and urinary creatinine, urea, uric acid, phosphorus, calcium, sodium, potassium, and chloride were altered. The co-administration of both RT extracts prevented alterations in all these parameters. In the EG/AC-induced rat model, the antioxidants- and polyphenols-rich E-RT and EA-RT extracts significantly reduced the presence of calcium oxalate in the urine, and prevented serum and urinary biochemical alterations together with kidney tissue damage associated with urolithiasis. Moreover, we demonstrated that the beneficial preventive effects of E-RT co-administration were more pronounced than those obtained with EA-RT. The superiority of E-RT was associated with its more potent antioxidant effect, due to its high content in polyphenols.

Tea and coffee consumption and the risk of urinary stones-a systematic review of the epidemiological data.

OBJECTIVE: To explore the relationship between the consumption of coffee and tea with urolithiasis. We evaluated large epidemiological and small clinical studies to draw conclusions regarding their lithogenic risk. METHODS: A systematic review was performed using the Medline and Scopus databases, in concordance with the PRISMA statement. English, French, and Spanish language studies regarding the consumption of caffeinated and decaffeinated coffee and tea, and the relationship to urinary stone disease were reviewed. Case reports and letters, unpublished studies, posters, and comments were excluded. RESULTS: As per the inclusion criteria, 13 studies were included in the final review. Most studies, including four large prospective studies and one meta-analysis, reported a reduced risk of stone formation for coffee and tea. Caffeine has a diuretic effect and increases the urinary excretion of calcium, but if these losses are compensated for, moderate caffeine intakes may have little or no deleterious effects. Green and Herbal teas infused for short time had low oxalate content compared to black tea. CONCLUSION: There is no evidence that moderate consumption of coffee raises the risk for stone formation in healthy individuals, provided the recommended daily fluid intake is maintained. The currently available literature supports in general a protective role for tea against the stone formation, mainly for green tea. However, heterogeneity of published data and lack of standardization needs to be addressed before final and clear conclusions can be given to patients and to the public in general.

Evaluation of diuretic efficacy and antiurolithiatic potential of ethanolic leaf extract of Annona squamosa Linn. in experimental animal models.

OBJECTIVE: The study is to investigate the diuretic and antiurolithiatic activities of ethanolic leaf extract of Annona squamosa Linn. in experimental animals. MATERIALS AND METHODS: For both studies, Wistar albino rats and two doses of extract (250 and 500 mg/kg) were used. Diuretic activity was evaluated by Lipschitz model. Urine volume and urine pH were noted, the concentration of sodium and potassium was estimated by flame photometry, and diuretic index, natriuretic index, and Lipschitz values were calculated from the results. Furosemide was used as a positive control. Ethylene glycol-induced urolithiasis model was used for antiurolithiatic study. Urine volume, urine pH, body weight, and biochemical parameters such as calcium, urea, uric acid, and creatine both from serum and urine were estimated. Antioxidant parameters and histopathological analysis of the kidney were evaluated. Cystone was used as a positive control in this study. Results were expressed as mean ± standard error of mean. Statistical analysis was carried out using one-way analysis of variance, followed by Dunnett's multiple comparison tests. RESULTS: In both diuretic and antiurolithiatic studies, both doses of the extract showed efficacy, and the dose of 500 mg/kg has shown a significant effect compared to positive control and negative control. CONCLUSION: The dose of 500 mg/kg showed a promising diuretic and antiurolithiatic activity.

Antiurolithiatic activity of Boldoa purpurascens aqueous extract: An in vitro and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Boldoa purpurascens Cav. (Nyctaginaceae) is a plant species used in traditional medicine in Cuba as antiurolithiatic. AIM OF THE STUDY: The aim of the present investigation was to evaluate the in vitro and in vivo antiurolothiatic activity of an aqueous extract from the leaves of Boldoa purpurascens. MATERIALS AND METHODS: The aqueous extract from leaves of Boldoa purpurascens was evaluated for antiurolithiatic activity in vitro and in vivo. In vitro crystallization of calcium oxalate (CaOx) was assessed using a nucleation, aggregation and growth assay. The effects of the extract and of Cystone®, used as a positive control, on the slope of nucleation and aggregation, as well as on the growth of CaOx crystals, were evaluated spectrophotometrically. The densities of the formed crystals were compared microscopically. In vivo activity was evaluated in an urolithiasis model in rats, in which kidney stones are induced by ethylene glycol (0.75%) and ammonium chloride (2%) in drinking water for 10 days. Three different experimental doses (100, 200 and 400 mg/kg, p.o.) of the extract and Cystone® were administered for 10 days. After 10 days, various biochemical parameters were measured in urine and serum, and histopathological analysis of the kidneys was carried out. RESULTS: The aqueous extract of Boldoa purpurascens inhibited the slope of nucleation and aggregation of CaOx crystallization, and decreased the crystal density. It also inhibited the growth and caused the dissolution of CaOx crystals. Cystone® exhibited similar effects. At a dose of 400 mg/kg the extract reduced the concentration of uric acid in urine, as well as the serum concentration of uric acid and creatinine. Histopathologic analysis of the kidneys of the same treatment group revealed reduced tissue damage; the results were almost similar to the untreated healthy control group. CONCLUSION: This study indicates that an aqueous leaf extract of Boldoa purpurascens may be effective in the prevention of urinary stone formation, and substantiates the traditional claim.

Molecular mechanisms involved in the protective effect of the chloroform extract of Selaginella lepidophylla (Hook. et Grev.) Spring in a lithiasic rat model.

Urolithiasis is a multifaceted process, progressing from urine supersaturation to the formation of mature renal calculi. Calcium oxalate, the main component of kidney stones, has toxicological effects on renal epithelial cells. Some medicinal plants have shown pharmacological effects against renal lithiasis, such as Selaginella lepidophylla (Hook. et Grev) Spring, a plant empirically used in Mexico for its diuretic and antilithiasic activity. The plant was identified and ground, and a chloroform extract (CE) was obtained. Urolithiasis was induced in Wistar female rats by administration of ethylene glycol and ammonium chloride for 21 days. Urolithiasis rats were treated with the CE (50 mg/kg) for 21 days. Osmolality, creatinine, sodium and potassium concentrations were measured in blood and urine. Glomerular filtration rate (GFR), and electrolytic and water balances were calculated. Urinary oxalic acid concentration was measured. Apoptosis, lipoperoxidation, ROS and p-amino hippuric acid were determined in cortical tissue. Urolithiasis rats showed a decrease of urinary flow, GFR, electrolytic balance, renal tubular secretion and ATP concentration and increase of urinary oxalic acid, lipoperoxidation, oxidative stress and apoptosis in cortical tissue. After treatment with the CE, urinary flow rate, GFR and renal tubular secretion levels were recovered; on the other hand, serum creatinine and urinary oxalic acid decreased on day 21. CE of Selaginella lepidophylla prevented the damage caused by lithiasic process by improving the active secretion in the proximal tubules, counteracting the ROS and lipoperoxidation effects by oxalate and decreased the OAT3 expression on kidney.

Plantas medicinais no controle de urolitíase / Using medicinal plants in the control of urolithiasis

Plantas medicinais têm sido utilizadas mundialmente para o controle de urolitíases na medicina humana. A ocorrência desta afecção tem aumentado em humanos, ruminantes, cães e gatos. Nos animais, fatores patofisiológicos adquiridos, congênitos ou familiares podem estar envolvidos, havendo similaridade ao que se observa em seres humanos. Porém, apesar dos avanços nas pesquisas, o emprego de plantas medicinais na medicina veterinária, ainda é pouco utilizado. Dessa forma, objetivou-se apresentar uma revisão bibliográfica dos resultados do uso de plantas medicinais no controle de urolitíase. As plantas utilizadas são: Ammi visnaga, Bergenia ligulata, Cynodon dactylon, Herniaria hirsuta e Phyllanthus niruri. A atividade antilitogênica foi relacionada às alterações da composição iônica da urina, atividade diurética, inibição de cristalização e agregação de cristais. Destaca-se o uso de Phyllanthus niruri, pela eficácia na prevenção dos urólitos. Extratos de Phyllanthus niruri normalizaram níveis altos de cálcio urinário, desfavorecendo os estágios iniciais de formação dos urólitos. Adicionalmente, foram associados à elevação da filtração glomerular e excreção urinária de ácido úrico sugerindo utilização potencial não só como efeito lítico e preventivo das calculoses, mas também em pacientes hiperuricêmicos e portadores de insuficiência renal. A partir dos resultados relatados, pode-se concluir que os trabalhos apresentados pela literatura atual são capazes de comprovar os efeitos benéficos do uso de plantas medicinais no controle de urolitíase. Entretanto, ainda são escassos os estudos realizados em animais domésticos, predominando ensaios desenvolvidos em roedores.

Medicinal plants have been used worldwide in the prevention of urolithiasis. The occurrence of this disease has increased in men, ruminants, dogs and cats. With regard to animals, acquired (congenital or hereditary) pathophysiological factors may be involved, a fact that bears similarity to what has been observed in humans. Yet, despite advances in research, the use of medicinal plants in veterinary medicine remains still underutilized. Thus, the purpose of this study is to conduct a literature review on the use of medicinal plants in the control of urolithiasis. The plants used are: Ammi visnaga, Bergenia ligulata, Cynodon dactylon, Herniaria hirsute and Phyllanthus niruri. Antilithogenic activity was related to changes in the ionic composition of urine, diuretic activity and inhibition of crystallization and aggregation of crystals. It is worth highlighting the use of Phyllanthus niruri due to its efficiency in the prevention of uroliths. Phyllanthus niruri extracts normalized high levels of urinary calcium, inhibiting the formation of uroliths in the initial stages. Additionally, they were associated with a higher glomerular filtration and higher urinary excretion of uric acid. These results suggest a potential use due to its lytic and preventive effect, as well as due to its application to hyperuricemic patients having renal insufficiency. We can conclude that the studies that pertain to the current literature can demonstrate the beneficial effects of using medicinal herbs to control urolithiasis. However, studies conducted in domestic animals remain scant, while tests developed in rodents still predominate.

[Treatment and metaphylaxis of gout complicated by nephropathy and urolithiasis].

The evaluation of clinical efficacy of combined treatment and metaphylaxis in 58 patients with gout complicated by nephropathy and urolithiasis was performed. The study included 41 (71%) men and 27 (29%) women aged 44 to 88 years (mean age - 58 +/- 7 years). All patients received parenteral therapy with trometamol H, 5 -10 infusion for the course, an average of 7 infusions. For the metaphylaxis, all patients received biologically active supplement urisan 2 tablets 2 times a day during next three months against the background of drug therapy. Findings indicate a high clinical efficacy of the trometamol H in the combined treatment of patients with gout, complicated by nephropathy and urolithiasis, considering that improvement of renal function, microcirculation in the renal parenchyma, increased glomerular filtration rate, normalization of nitrogenous wastes levels, partial or complete dissolution of concretions of the kidneys, a significant decrease in the tophs size, an increase in motor activity were observed, which ultimately improves the quality of life for these patients. Metaphylaxis using urisan for 3 months on a background of traditional therapy contributed to a stable normalization of blood uric acid levels, which prevented the exacerbation of underlying disease and recurrent stone formation. These data allow to recommend reducing the dose of traditional anti-gout drugs and conducting repeated course of metaphylaxis with the urisan after 5-6 months during 3 months.

Herbal medicines in the management of urolithiasis: alternative or complementary?

Kidney stone formation or urolithiasis is a complex process that results from a succession of several physicochemical events including supersaturation, nucleation, growth, aggregation, and retention within the kidneys. Epidemiological data have shown that calcium oxalate is the predominant mineral in a majority of kidney stones. Among the treatments used are extracorporeal shock wave lithotripsy (ESWL) and drug treatment. Even improved and besides the high cost that imposes, compelling data now suggest that exposure to shock waves in therapeutic doses may cause acute renal injury, decrease in renal function and an increase in stone recurrence. In addition, persistent residual stone fragments and the possibility of infection after ESWL represent a serious problem in the treatment of stones. Furthermore, in spite of substantial progress in the study of the biological and physical manifestations of kidney stones, there is no satisfactory drug to use in clinical therapy. Data from IN VITRO, IN VIVO and clinical trials reveal that phytotherapeutic agents could be useful as either an alternative or an adjunctive therapy in the management of urolithiasis. The present review therefore critically evaluates the potential usefulness of herbal medicines in the management of urolithiasis.

Role of overweight and obesity on the urinary excretion of promoters and inhibitors of stone formation in stone formers.

In recent decades there has been an increasing prevalence of urolitithiasis in many western countries and at the same time there has been an increasing progression of obesity that has reached epidemic proportions. The aim of the present study was to assess the influence of overweight/obesity on the metabolic risk factors for renal stone formation. We studied 799 renal stone formers (462 men and 337 women) who came to the clinic for metabolic risk factors evaluation. They were all studied with a standard protocol (two 24-h urine collections and serum parameters). They were divided according to their BMI in normal (BMI < 25) overweight (BMI 25-29.9) and obese (BMI > 30). Low-weight individuals were excluded. Overall, 487 of 799 (60.9%) patients had a BMI > 25, including 40.6% overweight and 20.3% obese. Among women 55.2% had normal weight, 25.5 were overweight, and 19.3% were Obese; among men 27.3% had normal weight, 51.7 were overweight, and 21% were obese. Age increased significantly with increasing BMI both in men and women. In women there was a significant increase in the excretion of oxalate, uric acid, phosphorus, creatinine, and sodium with increasing BMI, but no change was observed in calcium, magnesium, citrate, and urine pH. In men there was a significant increase in the excretion of oxalate, uric acid, creatinine, phosphorus, sodium, magnesium, and citrate with increasing BMI, no change in urinary calcium and significant progressive decrease in urinary pH. In this population of stone formers there was a high prevalence of overweight/obesity (60.9%). Both in men and women we found a significant increase in the urinary excretion of two promoters of stone formation, oxalate, and uric acid but no change in urinary calcium. There was either no change or increase in magnesium and citrate, inhibitors of crystallization, and a significant decrease in urine pH only in men.

Clinical study on the effect of mineral waters containing bicarbonate on the risk of urinary stone formation in patients with multiple episodes of CaOx-urolithiasis.

Investigations in healthy persons have shown that drinking mineral water containing HCO(3) has a positive effect on urine supersaturated with calcium oxalate (SS(CaOx)). The present study evaluates in a common setting whether these effects are also relevant in patients with multiepisodic urinary stone formation. A total of 34 patients with evident multiepisodic CaOx-urolithiasis were included in the study. Patients with hyperparathyroidism, renal tubular acidosis, Wilson's disease, Cushing disease, osteoporosis and malignant diseases were excluded. In a cross-over design and double-blinded the patients received 1.5 l of a mineral water with 2.673 mg HCO(3)/l (test water) or the same amount of water with a low mineral content (98 mg HCO(3)/l) (control water) daily for 3 days. During the study period the patients diet was recorded in a protocol, but not standardised. The main target parameter was SS(CaOx )in 24 h urine. In addition, urinary pH and the most important inhibiting and promoting factors were measured in 24 h urine (Ca, Ox, Mg, Cit). Both waters tested led to a highly significant increase in 24 h urine volume without a difference between each other. In the group, drinking the water containing HCO(3) the urinary pH increased significantly and was within a range relevant for metaphylaxis of calcium oxalate stone formation (x=6.73). This change was highly significant compared to the control group. In addition, significantly increased magnesium and citrate concentration were also observed. Supersaturation with calcium oxalate decreased significantly and to a relevant extent; however, there was no difference between the waters tested. As expected, the risk of uric acid precipitation also decreased significantly under bicarbonate water intake. However, an increase of the risk of calcium phosphate stone formation was observed. It is evident that both waters tested are able to lower significantly and to a relevant extent the risk of urinary stone formation in patients with multiepisodic CaOx-urolithiasis. In addition, the bicarbonate water increases the inhibitory factors citrate and magnesium due to its content of HCO(3) and Mg. Thus, it can be recommended for metaphylaxis of calcium oxalate and uric acid urinary stones.