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Herbo-Mineral Medicine, Lithom Exhibits Anti-Nephrolithiasis Activity in Rat Model of Hyperoxaluria by Attenuating Calcium Oxalate Crystal Formation and Oxidative Stress
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Vancomycin, is widely used against methicillin-resistant bacterial infections. However, Vancomycin accumulation causes nephrotoxicity which leads to an impairment in the filtration mechanisms of kidney. Traditional herbal medicines hold potential for treatment of drug-induced nephrotoxicity. Herein, we investigated protective properties of plant-based medicine Renogrit against Vancomycin-induced kidney injury. Phytometabolite analysis of Renogrit was performed by UHPLC. Spheroids formed from human proximal tubular cell (HK-2) were used for in vitro evaluation of Vancomycin-induced alterations in cell viability, P-gp functionality, NAG, KIM-1 levels, and mRNA expression of NGAL and MMP-7. The in vivo efficacy of Renogrit against Vancomycin-induced nephrotoxicity was further evaluated in Sprague-Dawley (SD) rats by measurement of BUN, serum creatinine, and their respective clearances. Moreover, eGFR, kidney-to-body weight ratio, GSH/GSSG ratio, KIM-1, NAG levels and mRNA expression of KIM-1 and osteopontin were also analyzed. Changes in histopathology of kidney and hematological parameters were also observed. Renogrit treatment led to an increase in cell viability, normalization of P-gp functionality, decrease in levels of NAG, KIM-1, and reduction in mRNA expression of NGAL and MMP-7. In Vancomycin-challenged SD rats, Renogrit treatment normalized altered kidney functions, histological, and hematological parameters. Our findings revealed that Renogrit holds a clinico-therapeutic potential for alleviating Vancomycin-associated nephrotoxicity.
This article reviews the beneficial and adverse effects of high-dose vitamin E supplementation on the vitamin E status and renal function in human and rodent studies. The high doses of vitamin E, which can cause renal effects, were compared to upper limits of toxicity (UL) as established by various authorities worldwide. In recent mice studies with higher doses of vitamin E, several biomarkers of tissue toxicity and inflammation were found to be significantly elevated. In these biomarker studies, the severity of inflammation and the increased levels of the biomarkers are discussed together with the need to re-evaluate ULs, given the toxic effects of vitamin E on the kidney and emphasizing oxidative stress and inflammation. The controversy in the literature about vitamin E effects on the kidney is mainly caused by the dose-effects relations that do not give a clear view, neither in human nor animals studies. In addition, more recent studies on rodents with new biomarkers of oxidative stress and inflammation give new insights into possible mechanisms. In this review, the controversy is shown and an advice given on the vitamin E supplementation for renal health.
Acute kidney injury (AKI) is a clinical syndrome that results from a rapid decline in renal structure or renal functional impairment with the main pathological feature of sublethal and lethal damage to renal tubular cells. However, many potential therapeutic agents cannot achieve the desired therapeutic effect because of their poor pharmacokinetics and short retention time in the kidneys. With the recent emergence and progress of nanotechnology, nanodrugs with unique physicochemical properties could prolong circulation time, enhance efficient targeted delivery, and elevate the accumulation of therapeutics that can cross the glomerular filtration barrier and indicate comprehensive application prospects in the prevention and treatment of AKI. In this review, various types of nanosystems (such as liposomes, polymeric nanosystems, inorganic nanoparticles and cell-derived extracellular vesicles) are designed and applied to improve the pharmacokinetics of drug formation, which could further relieve the burden on the kidneys caused by the final cumulative dose of drugs in conventional treatments. Moreover, the passive or active targeting effect of nanosystems can also reduce the total therapeutic dose and off-target adverse effects on other organs. Nanodelivery systems for treating AKI that alleviate oxidative stress-induced renal cell damage and regulate the inflammatory kidney microenvironment are summarized.
Purpose
To evaluate the safety and efficacy of single-probe dual-energy (SPDE) lithotripters in patients undergoing percutaneous nephrolithotripsy (PCNL) through a systematic review and meta-analysis.
Methods
We searched PubMed, Cochrane Library, Scopus and Embase databases until July 2022 for any preclinical or clinical studies, exploring the safety and efficacy of different SPDE lithotripters in patients undergoing PCNL. We performed a meta-analysis to compare stone-free rate, bleeding, or other complications and mean operative time between SPDE lithotripters and other lithotripters (PROSPERO: CRD42021285631).
Results
We included 16 studies (six preclinical, seven observational and three randomized with 625 participants) in the systematic review and four in the meta-analysis. Preclinical studies suggest that SPDE lithotripters are safe and effective for the management of renal stones. Among clinical studies, four studies assessed Trilogy with no comparative arm, two compared Trilogy or ShockPulse with a dual-probe dual-energy lithotripter, two compared Trilogy with a laser, one compared ShockPulse with a pneumatic lithotripter, and one directly compared Trilogy with ShockPulse. Comparing SPDE lithotripters to other lithotripters, no significant differences were demonstrated in stone free rate (OR 1.13, 95% CI 0.53–2.38, I² = 0%), postoperative blood transfusion (OR 1.33, 95% CI 0.34–5.19, I² = 0%), embolization (OR 0.45, 95% CI 0.02–12.06), operative time (WMD: 2.82 min, 95% CI −7.31–12.95, I² = 78%) and postoperative complications based on the Clavien–Dindo classification.
Conclusions
SPDE lithotripters represent a promising treatment modality for patients requiring PCNL. Despite the initial encouraging findings of preclinical and isolated clinical studies, it seems that Trilogy or ShockPulse provide similar efficiency compared to older generation devices.
Background
The prevalence of diabetes has considerably increased in recent years. In the long run, use of dual therapy of anti-diabetic agents becomes mandatory to attain euglycemia. Also, the incidences of diabetes-related co-morbidities have warranted the search for new therapeutic approaches for the management of the disease. Traditional herbo-mineral, anti-diabetic agents like Madhugrit are often prescribed to mitigate diabetes and related complications. The present study aimed to thoroughly characterize the pharmacological applications of Madhugrit.
Methods
Phytometabolite characterization of Madhugrit was performed by ultra-high performance liquid chromatography. Evaluation of cell viability, α-amylase inhibition, glucose uptake, inflammation, and wound healing was performed by in vitro model systems using AR42J, L6, THP1, HaCaT cells, and reporter cell lines namely NF-κB, TNF-α, and IL-1β. The formation of advanced glycation end products was determined by cell-free assay. In addition, the therapeutic potential of Madhugrit was also analyzed in the in vivo Caenorhabditis elegans model system. Parameters like brood size, % curling, glucose and triglyceride accumulation, lipid deposition, ROS generation, and lipid peroxidation were determined under hyperglycemic conditions induced by the addition of supraphysiological glucose levels.
Results
Madhugrit treatment significantly reduced the α-amylase release, enhanced glucose uptake, decreased AGEs formation, reduced differentiation of monocyte to macrophage, lowered the pro-inflammatory cytokine release, and enhanced wound healing in the in vitro hyperglycemic (glucose; 25 mM) conditions. In C. elegans stimulated with 100 mM glucose, Madhugrit (30 µg/ml) treatment normalized brood size, reduced curling behavior, decreased accumulation of glucose, triglycerides, and lowered oxidative stress.
Conclusions
Madhugrit showed multimodal approaches in combating hyperglycemia and related complications due to the presence of anti-diabetic, anti-inflammatory, anti-oxidant, wound healing, and lipid-lowering phytoconstituents in its arsenal. The study warrants the translational use of Madhugrit as an effective medicine for diabetes and associated co-morbidities.
Mitophagy is an essential mitochondrial quality control mechanism that eliminates damaged mitochondria and the production of reactive oxygen species (ROS). The relationship between mitochondria oxidative stress, ROS production and mitophagy are intimately interwoven, and these processes are all involved in various pathological conditions of acute kidney injury (AKI). The elimination of damaged mitochondria through mitophagy in mammals is a complicated process which involves several pathways. Furthermore, the interplay between mitophagy and different types of cell death, such as apoptosis, pyroptosis and ferroptosis in kidney injury is unclear. Here we will review recent advances in our understanding of the relationship between ROS and mitophagy, the different mitophagy pathways, the relationship between mitophagy and cell death, and the relevance of these processes in the pathogenesis of AKI.Abbreviations: AKI: acute kidney injury; AMBRA1: autophagy and beclin 1 regulator 1; ATP: adenosine triphosphate; BAK1: BCL2 antagonist/killer 1; BAX: BCL2 associated X, apoptosis regulator; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; BH3: BCL2 homology domain 3; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CASP1: caspase 1; CAT: catalase; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CI-AKI: contrast-induced acute kidney injury; CISD1: CDGSH iron sulfur domain 1; CL: cardiolipin; CNP: 2',3'-cyclic nucleotide 3'-phosphodiesterase; DNM1L/DRP1: dynamin 1 like; E3: enzyme 3; ETC: electron transport chain; FA: folic acid; FUNDC1: FUN14 domain containing 1; G3P: glycerol-3-phosphate; G6PD: glucose-6-phosphate dehydrogenase; GPX: glutathione peroxidase; GSH: glutathione; GSK3B: glycogen synthase kinase 3 beta; GSR: glutathione-disulfide reductase; HIF1A: hypoxia inducible factor 1 subunit alpha; HUWE1: HECT, UBA and WWE domain containing 1; IL1B: interleukin 1 beta; IMM: inner mitochondrial membrane; IPC: ischemic preconditioning; IRI: ischemia-reperfusion injury; LIR: LC3-interacting region; LPS: lipopolysaccharide; MA: malate-aspartate; MPT: mitochondrial permeability transition; MUL1: mitochondrial E3 ubiquitin protein ligase 1; mtROS: mitochondrial ROS; NLR: NOD-like receptor; NLRP3: NLR family pyrin domain containing 3; NOX: NADPH oxidase; OGD-R: oxygen-glucose deprivation-reperfusion; OMM: outer mitochondrial membrane; OPA1: OPA1 mitochondrial dynamin like GTPase; OXPHOS: oxidative phosphorylation; PARL: presenilin associated rhomboid like; PINK1: PTEN induced kinase 1; PLSCR3: phospholipid scramblase 3; PMP: peptidase, mitochondrial processing; PRDX: peroxiredoxin; PRKN: parkin RBR E3 ubiquitin protein ligase; RPTC: rat proximal tubular cells; ROS: reactive oxygen species; SLC7A11/xCT: solute carrier family 7 member 11; SOD: superoxide dismutase; SOR: superoxide reductase; SQSTM1/p62: sequestosome 1; TCA: tricarboxylic acid; TIMM: translocase of inner mitochondrial membrane; TOMM: translocase of outer mitochondrial membrane; TXN: thioredoxin; VDAC: voltage dependent anion channel; VCP: valosin containing protein.
Nephrolithiasis is a worldwide problem with increasing prevalence, enormous costs, and significant morbidity. Calcium-containing kidney stones are by far the most common kidney stones encountered in clinical practice. Consequently, hypercalciuria is the greatest risk factor for kidney stone formation. Hypercalciuria can result from enhanced intestinal absorption, increased bone resorption, or altered renal tubular transport. Kidney stone formation is complex and driven by high concentrations of calcium-oxalate or calcium-phosphate in the urine. After discussing the mechanism mediating renal calcium salt precipitation, we review recent discoveries in renal tubular calcium transport from the proximal tubule, thick ascending limb, and distal convolution. Furthermore, we address how calcium is absorbed from the intestine and mobilized from bone. The effect of acidosis on bone calcium resorption and urinary calcium excretion is also considered. Although recent discoveries provide insight into these processes, much remains to be understood in order to provide improved therapies for hypercalciuria and prevent kidney stone formation.
Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Urolithiasis is the third most common urological disease after urinary tract infections and prostate diseases, and it is characterised by an occurrence rate of about 15%, which continues to rise. The increase in the incidence of kidney stones observed in recent decades, is most likely caused by modifications in dietary habits (high content of protein, sodium and sugar diet) and lifestyle (reduced physical activity) in all industrialised countries. Moreover, men are more likely than women to be diagnosed with kidney stones. A growing body of evidence suggests that inflammation, oxidant–antioxidant imbalance, angiogenesis, purine metabolism and urea cycle disorders may play a crucial role in nephrolithiasis development. Patients with urolithiasis were characterised by an increased level of reactive oxygen species (ROS), the products of lipid peroxidation, proinflammatory cytokines as well as proangiogenic factors, compared to controls. Furthermore, it has been shown that deficiency and disorders of enzymes involved in purine metabolism and the urea cycle might be causes of deposit formation. ROS generation suggests that the course of kidney stones might be additionally potentiated by inflammation, purine metabolism and the urea cycle. On the other hand, ROS overproduction may induce activation of angiogenesis, and thus, allows deposit aggregation.
Background
In spite of advances in the modern allopathic medicines, there is no satisfactory treatment of kidney stones, so formation and growth of calculi continues to trouble mankind. In India, many herbal formulations are in use for the treatment of urolithiasis. The purpose of the present study was to investigate the antiurolithiatic efficacy of combined extract of plants Dolichos biflorus ( D.b ) (hydroalcoholic seed extract) and Crataeva nurvala ( C.n ) (aqueous bark extract) in ethylene glycol-induced urolithiasis in Wistar rats. Rats were divided into 4 groups. Ethylene glycol (0.75% v/v, p.o.) was administered for 35 days. Different drug treatments were given from the 21st to 35th day of the study. On the last day, rats were sacrificed, and different samples were taken for further analysis.
Results
Both the combination drug treatments were found to be effective in treating urolithiasis. More significant protection was observed on treatment with the fraction ratio of D.b + C.n (3:1). Histopathology analysis showed degenerated glomeruli and inflammatory cells in urolithiasis control. The same were regenerated on treatment with combined extract of the two plants.
Conclusion
Administration of the combined plant extracts in a ratio of D.b + C.n (3:1) possesses better efficacy against ethylene glycol-induced urolithiasis in rats which may be evaluated further for mechanistic pathway elucidation in vivo.
Bergenia (Saxifragaceae) genus is native to central Asia and encompasses 32 known species. Among these, nine are of pharmacological relevance. In the Indian system of traditional medicine (Ayurveda), "Pashanabheda" (stone breaker) is an elite drug formulation obtained from the rhizomes of B. ligulata. Bergenia species also possess several other biological activities like diuretic, antidiabetic, antitussive, insecticidal, anti-inflammatory, antipyretic, anti-bradykinin, antiviral, antibacterial, antimalarial, hepatoprotective, antiulcer, anticancer, antioxidant, antiobesity, and adaptogenic. This review provides explicit information on the traditional uses, phytochemistry, and pharmacological significance of the genus Bergenia. The extant literature concerned was systematically collected from various databases, weblinks, blogs, books, and theses to select 174 references for detailed analysis. To date, 152 chemical constituents have been identified and characterized from the genus Bergenia that belong to the chemical classes of polyphenols, phenolic-glycosides, lactones, quinones, sterols, tannins, terpenes, and others. B. crassifolia alone possesses 104 bioactive compounds. Meticulous pharmacological and phytochemical studies on Bergenia species and its conservation could yield more reliable compounds and products of pharmacological significance for better healthcare.
Calcium oxalate (CaOx) crystal deposition within the tubules is often a perplexing finding on renal biopsy of both native and transplanted kidneys. Understanding the underlying causes may help diagnosis and future management. The most frequent cause of CaOx crystal deposition within the kidney is hyperoxaluria. When this is seen in native kidney biopsy, primary hyperoxaluria must be considered and investigated further with biochemical and genetic tests. Secondary hyperoxaluria, for example due to enteric hyperoxaluria following bariatric surgery, ingested ethylene glycol or vitamin C overdose may also cause CaOx deposition in native kidneys. CaOx deposition is a frequent finding in renal transplant biopsy, often as a consequence of acute tubular necrosis and is associated with poorer long-term graft outcomes. CaOx crystal deposition in the renal transplant may also be secondary to any of the causes associated with this phenotype in the native kidney. The pathophysiology underlying CaOx deposition is complex but this histological phenotype may indicate serious underlying pathology and should always warrant further investigation.
Background:
Dietary and lifestyle factors may play an important role in the increasing prevalence of nephrolithiasis. We aimed to review and quantify the associations between lifestyle factors and incident nephrolithiasis and suggest lifestyle changes for the primary prevention of nephrolithiasis.
Methods:
PubMed, EMBASE, and Cochrane Library were searched up to May 2019, for observational studies and randomized controlled trials (RCTs) that assessed modifiable lifestyle factors and risk of nephrolithiasis in adults. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were computed using a random effects model. The I2 statistic was employed to evaluate heterogeneity. Subgroup analysis, sensitivity analysis and meta-regression were also conducted whenever possible.
Results:
Fifty relevant articles with 1,322,133 participants and 21,030 cases in total were identified. Prominent risk factors for incident stones were body mass index (1.39,1.27-1.52), dietary sodium (1.38, 1.21-1.56), fructose, meat, animal protein, and soda. In contrast, protective factors included fluid intake (0.55, 0.51-0.60), a Dietary Approaches to Stop Hypertension (DASH) style diet (0.69, 0.64-0.75), alcohol (0.69, 0.56-0.85), water, coffee, tea, vegetables, fruits, dietary fiber, dietary calcium (0.83, 0.76-0.90), and potassium. Vitamin D (1.22, 1.01-1.49) and calcium (1.16, 1.00-1.35) supplementation alone increased the risk of stones in meta-analyses of observational studies, but not in RCTs, where the cosupplementation conferred significant risk.
Conclusions:
Several modifiable factors, notably fluid intake, dietary patterns, and obesity, were significantly associated with nephrolithiasis. Long-term RCTs are required to investigate the cost-effectiveness of dietary patterns for stone prevention. The independent and combined effects of vitamin D and calcium supplementation on nephrolithiasis need further elucidation.
Introduction Due to unavailability of potent drug for treatment of urolithiasis and its reoccurrence, the interest is increasing for study of natural products with anti-urolithiatic activity having fewer side effects. The present study was aimed to examine the anti-urolithiatic property of methanolic extract of Crataeva nurvala root and bark for in vivo, in comparison to popular herbal standard Cystone. Method Mice were divided into seven groups. Group I act as normal control group and group II serve as negative control. Group II to group VII were given normal diet and pure drinking water containing ethylene glycol and ammonium chloride. Group III was taken as standard whereas Group IV to VII were taken as test group. Test group were fed with 150 mg/kg and 300 mg/kg of both bark and root extract where as a standard group was supplied with Cystone at dose of 750 mg/kg. At 11 th day of treatment, urine was analyzed for total biochemical parameters namely uric acid, calcium and magnesium along with total urinary volume per day. Result The result showed that both root and bark extract of plant have effective antiurolithiatic effect. Among them, root extract at the concentration of 300 mg/kg performed most significant activity which is almost similar to standard. Conclusion Our study revealed that, C. nurval root can be the best alternative for ayurvedic drug as it alone can show the potent anti-urolithiatic activity almost similar to poly herbal drug .
Background: Mutrashmari (urinary stones) is one among the Ashtamahagada (eight fatal conditions) and is Kaphapradhan Tridoshaja
Vyadhi, which is correlated with urolithiasis. It is the major cause of morbidity. The lifetime prevalence of symptomatic urolithiasis
is approximately 10% in men and 5% in women. Many treatment modalities have been adopted in medical sciences, but it is quite
expensive and also the pathogenesis behind recurrence of formation of stone cannot be avoided. Hence, it is necessary to find out an
economical effective, easily available medicine to treat Mutrashmari. Objectives: The aim of this study was to evaluate the efficacy of
Shaman Chikitsa in Mutrashmari w.r.t. to urolithiasis. Materials and Methods: It is a single case study. A 50-year-old man who was
already diagnosed before 20 years approached to outpatient department of Panchakarma with complaints of pain in abdomen and
back, which was radiating from loin to groin region; burning micturition; and dysuria. The patient was administered with Shaman
Aushadhi. Results: The patient got 80% results in chief and associated complaints, and during and after the completion of therapy
there was an improvement in the quality of life of the patient. Conclusion: Satisfactory relief in symptoms was seen in patient after 1
month of Shaman Chikitsa.
Keywords: Mutrashmari, Shaman Chikitsa, urolithiasis
Understanding the mechanisms of kidney stone formation, development patterns and associated pathological features are gaining importance due to an increase in the prevalence of the disease and diversity in the presentation of the stone composition. Based on the micro-structural characteristics of kidney stones, it may be possible to explain the differences in the pathogenesis of pure and mixed types of stones. In this study, the microstructure and distribution of mineral components of kidney stones of different mineralogy (pure and mixed types) were analyzed. The intact stones removed from patients were investigated using synchrotron radiation X-ray computed microtomography (SR-μCT) and the tomography slice images were reconstructed representing the density and structure distribution at various elevation planes. Infrared (IR) spectroscopes, X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to confirm the bulk mineral composition in the thin section stones. Observations revealed differences in the micro-morphology of the kidney stones with similar composition in the internal 3-D structure. Calcium oxalate monohydrate stones showed well-organised layering patterns, while uric acid stones showed lower absorption signals with homogenous inner structure. Distinct mineral phases in the mixed types were identified based on the differential absorption rates. The 3-D quantitative analysis of internal porosity and spatial variation between nine different types of stones were compared. The diversity among the microstructure of similar and different types of stones shows that the stone formation is complex and may be governed by both physiological and micro-environmental factors. These factors may predispose a few towards crystal aggregation and stone growth, while, in others the crystals may not establish stable attachment and/or growth.
Background
Thiazide diuretics are commonly prescribed to prevent kidney stones. However, it is unclear whether higher doses confer greater benefit.
Objective
To determine whether lower doses of thiazide diuretics confer a similar protective effect against kidney stone events as higher doses.
Design
Population-based cohort study.
Setting
Linked health administrative databases in Ontario, Canada.
Patients
Older adults newly prescribed a thiazide diuretic between 2003 and 2014 were separated into 2 groups based on daily dose: low dose (⩽12.5 mg hydrochlorothiazide/chlorthalidone, or ⩽1.25 mg indapamide) or high dose.
Measurements
The primary outcome was time to a kidney stone event, using diagnosis and procedure codes. A secondary outcome was kidney stone surgery.
Methods
An association between thiazide diuretic dose and a kidney stone event was estimated using Cox proportional hazards regression.
Results
A total of 536 of 105 239 patients (0.51%) experienced a kidney stone event. We did not detect a difference in kidney stone risk in the high-dose relative to the low-dose group (adjusted hazard ratio, 1.10; 95% confidence interval, 0.93-1.31). Results were similar when analysis was restricted to the more specific outcome of kidney stone surgery. Neither a history of prior kidney stones nor the type of thiazide diuretic modified the effect of diuretic dose on outcome.
Limitations
Patients were >65 years old and we were unable to adjust for some potential confounders such as dietary factors.
Conclusions
Lower dose thiazide diuretics appear to confer a similar protective effect as higher dose thiazides against the development of kidney stones.
Crystal aggregation is one of the most crucial steps in kidney stone pathogenesis. However, previous studies of crystal aggregation were rarely done and quantitative analysis of aggregation degree was handicapped by a lack of the standard measurement. We thus performed an in vitro assay to generate aggregation of calcium oxalate monohydrate (COM) crystals with various concentrations (25–800 μg/ml) in saturated aggregation buffer. The crystal aggregates were analyzed by microscopic examination, UV-visible spectrophotometry, and GraphPad Prism6 software to define a total of 12 aggregation indices (including number of aggregates, aggregated mass index, optical density, aggregation coefficient, span, number of aggregates at plateau time-point, aggregated area index, aggregated diameter index, aggregated symmetry index, time constant, half-life, and rate constant). The data showed linear correlation between crystal concentration and almost all of these indices, except only for rate constant. Among these, number of aggregates provided the greatest regression coefficient (r = 0.997; p < 0.001), whereas the equally second rank included aggregated mass index and optical density (r = 0.993; p < 0.001 and r = −0.993; p < 0.001, respectively) and the equally forth were aggregation coefficient and span (r = 0.991; p < 0.001 for both). These five indices are thus recommended as the most appropriate indices for quantitative analysis of COM crystal aggregation in vitro.
Background and objective
The purpose of the current investigation was to study the influences, preventive and diuretic, of Nigella sativa L. seeds oil (NSSO) on calcium oxalate (CaOx) urolithiasis induced in Wistar male rats.
Methodology
Seeds of Nigella sativa L. (N.S) were analysed for the evaluation of the concentration of oxalate and calcium. Nigella sativa L. seeds oil is obtained by hydrodistillation and HPTLC densitometric method was adopted to determine the amount of thymoquinone (TQ) present.
Thirty male Wistar rats were divided into 5 groups (N=6). Group I, negative control, drank tap water. The other groups were II Positive control, III, IV and V received a treatment model inducing calcium oxalate urolithiasis for 28 days, using an aqueous solution involve 0.75% (EG) ethylene glycol and 1.0 % (AC) chloride ammonium. Rats in group III received in addition, 750 mg/kg Cystone from the beginning to the end of calculi induction experimentation.
However, rats in Groups IV and V received (NSSO) at 5 ml/kg b.w by gavage on days 1st to 28th and 15th to 28th days, respectively. On days 0, 7, 14, 21 and 28, body weights were measured and the 24-hour urine samples were accumulated and analysed for biochemical elements. On the 28th day, blood samples were collected for the estimation of serum parameters including creatinine, BUN and uric acid.
All animals were sacrificed at the end of the experiment and the kidneys were detached for histopathological examination.
Results
Administration of (NSSO) at 5 ml/kg body weight/dose/day for 28 days exerts a protective effect by reducing significantly (p <0.01) urinary and serum rates of calcium, phosphate and oxalate. This preventive diet could increase the volume of urine excreted.
Conclusion
The nephroprotectrice and diuretic activity demonstrated by Nigella sativa L. gives a scientific basis that approves their traditional use like a remedy against urolithiasis.
List of Abbreviations:NSSO: Nigella sativa L. Seeds oil ; CaOx: Calcium Oxalate; N.S: Nigella sativa L.; HPTLC: High performance thin layer chromatography; TQ: Thymoquinone; N: Number; EG: Ethylene Glycol; AC: Chloride Ammonium BUN: Blood Urea Nitrogen; LD50: Lethal Dose 50; b.w: body weight; H & E: Haematoxyline and Eosin; HPLC-UV:;Caph: calcium phosphate; FR: glomerular filtration rate
Dried rhizome of Bergenia ligulata (pashanbhed) is commonly used as a traditional herbal medicine with a wide range of therapeutic applications including urolithiasis. Aqueous extract of B. ligulata was prepared through maceration followed by decoction (mother extract, 35.9% w/w). Further, polarity based fractions were prepared successively from mother extract which yielded 3.4, 2.9, 5.4, 7.5, and 11.3% w/w of hexane, toluene, dichloromethane (DCM), n -butanol, and water fractions, respectively. The in vitro, ex vivo, and real-time antiurolithiasis activity of mother extract and fractions were carried out using aggregation assay in synthetic urine and in rat plasma. The study revealed that DCM fraction has significantly ( p<0.05 ) greater inhibitory potential than other fractions. Ethylene glycol in drinking water (0.75%, v/v) for 28 days was used for induction of urolithiasis and the curative effects of mother extract and DCM fraction were checked for the level of oxalate, calcium, creatinine, uric acid, and urea of both urine and serum. Treatment with mother extract and DCM fraction at a dose of 185 mg/kg and 7 mg/kg, respectively, in ethylene glycol induced rats resulted in a significant ( p<0.05 ) decrease in serum and urine markers. Histological study revealed lower number of calcium oxalate deposits with minimum damage in the kidneys of mother extract and DCM fraction treated rats. This result provides a scientific basis for its traditional claims.
Oxidative stress is a causal factor and key promoter of urolithiasis associated with renal tubular epithelium cell injury. The present study was designed to investigate the preventive effects of metformin on renal tubular cell injury induced by oxalate and stone formation in a hyperoxaluric rat model. MTT assays were carried out to determine the protection of metformin from oxalate-induced cytotoxicity. The intracellular superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured in vitro. Male Sprague-Dawley rats were divided into control group, ethylene glycol (EG) treated group, and EG + metformin treated group. Oxidative stress and crystal formations were evaluated in renal tissues after 8-week treatment. Metformin significantly inhibited the decrease of the viability in MDCK cells and HK-2 cells induced by oxalate. Besides, metformin markedly prevented the increased concentration of MDA and the decreased tendency of SOD in oxalate-induced MDCK cells and HK-2 cells. In vivo, the increased MDA levels and the reduction of SOD activity were detected in the EG treated group compared with controls, while these parameters reversed in the EG + metformin treated group. Kidney crystal formation in the EG + metformin treated group was decreased significantly compared with the EG treated group. Metformin suppressed urinary crystal deposit formation through renal tubular cell protection and antioxidative effects.
Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers, when initiating new animal or human experiments. Interspecies allometric scaling for dose conversion from animal to human studies is one of the most controversial areas in clinical pharmacology. Allometric approach considers the differences in body surface area, which is associate with animal weight, while extrapolating the doses of therapeutic agents among the species. This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling. The method of calculation of injection volume of parenteral formulation based on human equivalent dose is also briefed.
The incidence of kidney stones is common in the United States and treatments for them are very costly. This review article provides information about epidemiology, mechanism, diagnosis, and pathophysiology of kidney stone formation, and methods for the evaluation of stone risks for new and follow-up patients. Adequate evaluation and management can prevent recurrence of stones. Kidney stone prevention should be individualized in both its medical and dietary management, keeping in mind the specific risks involved for each type of stones. Recognition of these risk factors and development of long-term management strategies for dealing with them are the most effective ways to prevent recurrence of kidney stones.
Fenugreek is one of several herbal medicines whose seeds and leaves are used either as food or as an ingredient in folk medicine. In the existing literature, there is evidence regarding the effects of fenugreek on ethylene glycol induced kidney stone formation of rats. Regarding the other drugs, such as Cystone, the seeds of Trigonella foenum-graecum (fenugreek) are reported to have been used as anti-urolithiatic in traditional medicine. Thus, the present study was undertaken to investigate the effect of fenugreek on the prevention of kidney stone formation. Twenty male albino rats were divided into 4 groups: Normal, Ethylene Glycol (EG), Cystone and Fenugreek. The duration of the experiment was 28 days. Ethylene glycol group led to increases in kidney weight, malondialdehyde (MDA) and platelet count, while Cystone and Fenugreek combat the effect of EG. Haematological examination showed that the hemoglobin and red blood cell count in rats treated EG were significantly lower than those in the controls while Fenugreek and Cystone decreased the EG effect. Our studies demonstrate the anti-urolithiatic and anti-oxidative potential effects of T. foenum-graecum, which could exert beneficial effects against the kidney stone formation and the associated free radicals complications in kidney tissues. Further clinical trials are needed for evaluating its benefits and the possible side effects.
Tribulus terrestris (family Zygophyllaceae), commonly known as Gokshur or Gokharu or puncture vine, has been used for a long time in both the Indian and Chinese systems of medicine for treatment of various kinds of diseases. Its various parts contain a variety of chemical constituents which are medicinally important, such as flavonoids, flavonol glycosides, steroidal saponins, and alkaloids. It has diuretic, aphrodisiac, antiurolithic, immunomodulatory, antidiabetic, absorption enhancing, hypolipidemic, cardiotonic, central nervous system, hepatoprotective, anti-inflammatory, analgesic, antispasmodic, anticancer, antibacterial, anthelmintic, larvicidal, and anticariogenic activities. For the last few decades or so, extensive research work has been done to prove its biological activities and the pharmacology of its extracts. The aim of this review is to create a database for further investigations of the discovered phytochemical and pharmacological properties of this plant to promote research. This will help in confirmation of its traditional use along with its value-added utility, eventually leading to higher revenues from the plant.
Food is the major source for serving the nutritional needs, but with growing modernization some traditional ways are being given up. Affluence of working population with changing lifestyles and reducing affordability of sick care, in terms of time and money involved, are some of the forces that are presently driving people towards thinking about their wellness. There has been increased global interest in traditional medicine. Efforts to monitor and regulate traditional herbal medicine are underway. Ayurveda, the traditional Indian medicine, remains the most ancient yet living traditions. Although India has been successful in promoting its therapies with more research and science-based approach, it still needs more extensive research and evidence base. Increased side effects, lack of curative treatment for several chronic diseases, high cost of new drugs, microbial resistance and emerging, diseases are some reasons for renewed public interest in complementary and alternative medicines. Numerous nutraceutical combinations have entered the international market through exploration of ethnopharmacological claims made by different traditional practices. This review gives an overview of the Ayurvedic system of medicine and its role in translational medicine in order to overcome malnutrition and related disorders.
Adhesion of calcium oxalate (CaOx) crystals to kidney cells is a key event in kidney stones associated with marked hyperoxaluria. As the propensity of stone recurrence and persistent side effects are not altered by surgical techniques available, phytotherapeutic agents could be useful as an adjuvant therapy. The present study is aimed at examining the antilithiatic potency of the protein biomolecules of Tribulus terrestris, a plant which is a common constituent of herbal marketed preparations to treat urolithiasis. Various biochemical methods with mass spectrometry were used to purify and characterize the purified protein. The protective potency of the protein was tested on the oxalate induced injury on renal epithelial cell lines (NRK 52E). An antilithiatic protein having molecular weight of ~ 60kDa was purified. This purified protein showed similarities with Carotenoid cleavage dioxygenase 7 (CCD7) of Arabidopsis thaliana after matching peptide mass fingerprints in MASCOT search engine. An EF hand domain was identified in CCD7 by SCAN PROSITE. Presence of an EF hand domain, a characteristic feature of calcium binding proteins and a role in the synthesis of retinol which is transported by retinol binding protein, a protein found in kidney stone matrix; of CCD7 support the role of TTP as an antilithiatic protein. The protective potency of TTP on NRK 52E was quite comparable to the aqueous extract of cystone. Our findings suggest that this purified protein biomolecule from Tribulus terrestris could open new vista in medical management of urolithiasis.
We have reviewed the general mechanisms involved in kidney stone formation, with reference to those composed of calcium oxalate
or phosphate, uric acid, and cystine. These processes include nucleation of individual crystals, aggregation or secondary
nucleation to produce small intrarenal multicrystalline aggregates, fixation within the kidney, and further aggregation and
secondary nucleation to produce the clinical stone. The factors regulating these processes have been discussed as well as
the effects of tubular fluid or urine pH and promoters or inhibitors, including urate or uric acid in the case of calcium
oxalate stones, citrate, pyrophosphate, phytate, and urinary proteins. We also discuss the potential for macromolecular inhibitors
to actually promote stone formation when they are fixed to some intrarenal structure or if they themselves become aggregated
into protein–protein complexes.
There is considerable interest in the role that mammalian heme peroxidase enzymes, primarily myeloperoxidase, eosinophil peroxidase and lactoperoxidase, may play in a wide range of human pathologies. This has been sparked by rapid developments in our understanding of the basic biochemistry of these enzymes, a greater understanding of the basic chemistry and biochemistry of the oxidants formed by these species, the development of biomarkers that can be used damage induced by these oxidants in vivo, and the recent identification of a number of compounds that show promise as inhibitors of these enzymes. Such compounds offer the possibility of modulating damage in a number of human pathologies. This reviews recent developments in our understanding of the biochemistry of myeloperoxidase, the oxidants that this enzyme generates, and the use of inhibitors to inhibit such damage.
Treatment with cationic amphiphilic drugs like Amiodarone leads to development of phospholipidosis, a type of lysosomal storage disorder characterized by excessive deposition of phospholipids. Such disorder in liver enhances accumulation of drugs and its metabolites, and dysregulates lipid profiles, which subsequently leads to hepatotoxicity. In the present study, we assessed pharmacological effects of herbal medicine, Livogrit, against hepatic phospholipidosis-induced toxicity. Human liver (HepG2) cells and in vivo model of Caenorhabditis elegans (N2 and CF1553 strains) were used to study effect of Livogrit on Amiodarone-induced phospholipidosis. In HepG2 cells, Livogrit treatment displayed enhanced uptake of acidic pH-based stains and reduced phospholipid accumulation, oxidative stress, AST, ALT, cholesterol levels, and gene expression of SCD-1 and LSS. Protein levels of LPLA2 were also normalized. Livogrit treatment restored Pgp functionality which led to decreased cellular accumulation of Amiodarone as observed by UHPLC analysis. In C. elegans, Livogrit prevented ROS generation, fat-6/7 gene overexpression, and lysosomal trapping of Amiodarone in N2 strain. SOD-3::GFP expression in CF1553 strain normalized by Livogrit treatment. Livogrit regulates phospholipidosis by regulation of redox homeostasis, phospholipid anabolism, and Pgp functionality hindered by lysosomal trapping of Amiodarone. Livogrit could be a potential therapeutic intervention for amelioration of drug-induced phospholipidosis and prevent hepatotoxicity.
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a disorder in which urinary solutes precipitate to form aggregates of crystalline material in the urinary space. The incidence of nephrolithiasis has been increasing, and the demographics have been evolving. Once viewed as a limited disease with intermittent exacerbations that are simply managed by urologists, nephrolithiasis is now recognized as a complex condition requiring thorough evaluation and multifaceted care. Kidney stones are frequently manifestations of underlying systemic medical conditions such as the metabolic syndrome, genetic disorders, or endocrinopathies. Analysis of urine chemistries and stone composition provide a window into pathogenesis and direct ancillary studies to uncover underlying diseases. These studies allow providers to devise individualized strategies to limit future stone events. Given its complexity, kidney stone disease is best addressed by a team led by nephrologists and urologists with input from multiple other health professionals including dietitians, endocrinologists, interventional radiologists, and endocrine surgeons. In this installment of AJKD's Core Curriculum in Nephrology, we provide a case-based overview of nephrolithiasis, divided by the individual stone types. The reader will gain a pragmatic understanding of the pathophysiology, evaluation, and management of this condition.
Diabetes mellitus is a disease characterized by hyperglycemia. Chronic hyperglycemia indiabetes mellitus can cause various complications, one of which is diabetic nephropathy,which affects the kidney. Chronic hyperglycemia causes an increase in free radicals and adecrease in antioxidant activity resulting in oxidative stress conditions. This study aims to determine kidney damage caused by oxidative stress and the role of antioxidants in reducingthis damage through literature studies. The literature used comes from Google search results such as PubMed, Google Scholar, ResearchGate, and ScienceDirect. From the search results, ten journals meeting the inclusion and exclusion criteria were selected for review and comparison so that a conclusion could be drawn. The results of this literature study have demonstrated that biochemical parameters, such as increased levels of creatinine, urea, malondialdehyde (MDA), and decreased antioxidant enzymes, as well as kidney histological parameters, such as changes in the shape of tubules, glomeruli, and increased kidney expression, are indicators of kidney damage caused by oxidative stress. The mechanism of antioxidants in reducing kidney damage is through DNA cutting, binding to phenolic OH groups, down-regulation of the oxidase expression of nitrogen oxides 4 nicotinamide adenine dinucleotide phosphate (Nox4 NADPH), antioxidant enzyme systems, activation of the activated protein kinase pathway - silent mating type information regulation 2 homolog 1- peroxisome proliferator-activated receptor-γ coactivator 1α (AMPK-SirT1- PGC-1 α), protein glycation reactions, and inhibition of protein 53 (P53) so that erythroid nuclear factor 2-related factor 2 (Nrf2) can activate antioxidant gene transcription.
Nephrolithiasis affects a significant proportion of people today as a result of changing lifestyles. A number of physicochemical processes within the kidney lead to the development of nephrolithiasis, also known as kidney stones. Sadly, there isn't a good drug that can be used in clinical treatment. Natural remedies have been utilized for the treatment of kidney stones for years and are still in use today, serving as solutions in many circumstances since they are effective, socially acceptable, and have less adverse effects than pharmaceutical treatments. We have given an overview of these natural substances in this chapter, together with information on their primary chemical components and potential modes of action. The findings in this chapter show the prospective role that natural products can play in the prevention and management of kidney stones.
Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease (ESRD), and the prevalence of DKD has increased worldwide during recent years. DKD is associated with poor therapeutic outcomes in most patients, but there is limited understanding of its pathogenesis. This review suggests that oxidative stress interacts with many other factors in causing DKD. Highly active mitochondria and NAD(P)H oxidase are major sources of oxidants, and they significantly affect the risk for DKD. Oxidative stress and inflammation may be considered reciprocal causes of DKD, in that each is a cause and an effect of DKD. Reactive oxygen species (ROS) can act as second messengers in various signaling pathways and as regulators of metabolism, activation, proliferation, differentiation, and apoptosis of immune cells. Epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs can modulate oxidative stress. The development of new technologies and identification of new epigenetic mechanisms may provide novel opportunities for the diagnosis and treatment of DKD. Clinical trials demonstrated that novel therapies which reduce oxidative stress can slow the progression of DKD. These therapies include the NRF2 activator bardoxolone methyl, new blood glucose-lowering drugs such as sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists. Future studies should focus on improving early diagnosis and the development of more effective combination treatments for this multifactorial disease.
The herb Boerhavia diffusa (BD) is well-known in the Indian medicinal system. Punarnava is its vernacular name. BD is one of the chief ingredients in ayurvedic formulations used for urinary diseases. In the realm of phytochemistry, the plant has risen to prominence due to its diverse biological activities. Here, we reviewed the scientific literature available on administration of BD for acute kidney injury, chronic kidney disease, polycystic kidney disease, renal calculi, urinary tract infection, and COVID-19 related kidney disease and we also explored its antioxidant and anti-inflammatory properties. The nephroprotective effect of BD has been clearly demonstrated in in vitro, in vivo, and in clinical studies. The in vivo studies have yielded a plethora of data. The most commonly employed extracts were aqueous, hydroalcoholic, ethanolic, and methanolic extracts. Clinical studies have employed polyherbal combinations containing BD extract. Irrespective of the type of BD extract, all studies showed reduction in the key markers of kidney diseases, namely urea, creatinine, BUN, and proteins. It has antifibrotic property reducing the formation of extracelluar collagen deposition in the renal tubules, which is not much explored. The review highlights the importance of further research required in establishing the molecular mechanisms underlying the action of BD. With in-depth molecular research and clinical trials, BD could be developed into a novel therapeutic agent for the successful treatment of renal disorders especially the chronic kidney disease.
Atherosclerosis is the main pathological process of several cardiovascular diseases. It may begin early in life and stay latent and asymptomatic for an extended period before its clinical manifestation. The formation of foamy macrophages due to dysregulated lipid metabolism is a key event in the development and progression of atherosclerotic plaque. The current pharmacotherapy for atherosclerosis is not able to address multiple aetiologies associated with the disease. Lipidom, an herbal prescription medicine, has anti-oxidant, lipid lowering and anti-inflammatory properties that lead to multifaceted treatment benefits against chronic inflammation, dyslipidaemia, and oxidative stress. The present study aimed to characterize the pharmacological effects of Lipidom using various experimental models. The phytochemical analysis of Lipidom was performed on ultra-high performance liquid chromatography (UHPLC) platform. Lipidom was evaluated for cytosafety, IL-1β and MCP-1 release, modulation of NLRP3 pathway, NFκB activity, ROS generation, lipid accumulation and gene expression in THP1 macrophages. Furthermore, Lipidom evaluation was also performed in the N2, CF1553, and TJ356 strains of Caenorhabditis elegans (C. elegans). The evaluation of brood size, adult (%), lipid accumulation, triglyceride levels, SOD-3 GFP signal, MDA formation, DAF-16 nuclear translocation, and gene expression was performed in C. elegans. Lipidom treatment significantly reduced the inflammatory mediators, lipid accumulation, oxidative stress, and normalized genes involved in the development of foamy macrophages. Lipidom treated C. elegans showed a significant decline in lipid accumulation and oxidative stress. Taken together, Lipidom treatment showed a multifaceted approach in the modulation of several mediators responsible for the development and progression of atherosclerotic plaque.
Chronic kidney disease (CKD) is associated with a variety of distinct disease processes that permanently change the function and structure of the kidney across months or years. CKD is characterized as a glomerular filtration defect or proteinuria that lasts longer than three months. In most instances, CKD leads to end-stage kidney disease (ESKD), necessitating kidney transplantation. Mitochondrial dysfunction is a typical response to damage in CKD patients. Despite the abundance of mitochondria in the kidneys, variations in mitochondrial morphological and functional characteristics have been associated with kidney inflammatory responses and injury during CKD. Despite these variations, CKD is frequently used to define some classic signs of mitochondrial dysfunction, including altered mitochondrial shape and remodeling, increased mitochondrial oxidative stress, and a marked decline in mitochondrial biogenesis and ATP generation. With a focus on the most significant developments and novel understandings of the involvement of mitochondrial remodeling in the course of CKD, this article offers a summary of the most recent advances in the sources of procured mitochondrial dysfunction in the advancement of CKD. Understanding mitochondrial biology and function is crucial for developing viable treatment options for CKD.
Background
The plant species belonging to the genus Boerhavia (Nyctaginaceae) have been used extensively in ethnomedicine and Ayurveda in India. Raktapunarnava and Shweta punarnava are two of the species which find mention in various Ayurvedic formulations. Other species of Boerhavia, though not found in Indian system of medicine, do hold importance in ethnomedicine systems in India and other countries.
Objective
Boerhavia being a polymorphic genus, has been treated as a single genus encompassing species belonging to a morphologically related genus Commicarpus also. Owing to this taxonomic quandary with regard to merger or separation of the two genera by different workers, there are different reports of the number of species belonging to the genus. This has further resulted in flawed reporting of ethnomedicinal as well as ethnopharmacological studies. The present review focuses on resolving any confusion in taxonomic treatment, to highlight the ethnomedicinal uses supported by ethnopharmcological data and the phytochemistry of Boerhavia and Commicarpus species found in India.
Conclusion
In India four species of Boerhavia and two species belong to Commicarpus have been reported to occur. The literature survey revealed that except B. diffusa, no other species of Boerhavia has been explored in detail. This presents an opportunity to undertake research on Boerhavia species and find new phytochemicals with promising therapeutic effects.
Background
Chronic kidney disease (CKD) and end-stage renal diseases, has high global morbidity and mortality.
Objective
We aimed to investigate the antioxidant and anti-inflammatory properties of curcumin and its impact on kidney biochemical parameters associated with kidney disease among CKD and hemodialysis (HD) patients.
Methods
The intended keywords were used in the literature search. Clinical trial studies from the very beginning to December 25th, 2021, indexed in the Institute for Scientific Information (ISI), Scopus, and PubMed databases were included in the review. Records with no accessible full texts, non-English language articles, and studies that were not related to the study aim were excluded. The agreement for exclusion required all authors to concur. Finally, after reviewing all available literature, 27 articles were included in this systematic review.
Results
Curcumin supplementation increased antioxidant capacity by improving catalase (CAT) activity, free radical scavenging activity, and, nuclear factor erythroid 2–related factor 2 (Nrf2). It also reduced hs-CRP, IL-6, and, TNF-a levels in patients with CKD and HD patients. Different results were reported regarding the effect of curcumin on kidney-related biochemical parameters. But mostly the results showed that there are no significant changes were seen in glomerular filtration (GFR), albumin (Alb), serum creatinine (sCr), proteinuria (PRO), and blood urea nitrogen (BUN) in these patients.
Conclusion
Although it seems curcumin improved antioxidant capacity and decreased inflammatory cytokines in CKD and HD patients, it did not affect renal biochemical parameters. More clinical studies with larger sample sizes appear to be needed.
Although nephrolithiasis is a more common disease in men rather than women, several studies over the last decades show that the male to female ratio 3:1 is narrowing. These finding may be associated to modified risk factors for stone formation between females and males. Changes in lifestyle and increasing obesity in women may play a role in shifting of gender disparity. Furthermore, recent studies have demonstrated an increase of kidney stones in women which have necessitated emergency department visits (ED). Therefore, females show a greater percentage of mortality rate if compared to males, especially if stone disease is associated to urosepsis and requires the admission to the Intensive Care Unit (ICU). This article reviews recent insights into changing gender prevalence in urinary calculi and into identifying the relation between gender and risk factors for stone disease, that in case of severe urosepsis might also lead to mortality.
Urolithiasis is a most common health problem seen amongst most of the population suffering from the recurrence of kidney stones composed of calcium and oxalate crystals. Although the various conventional therapies are available for the urothialisis, the recurrence of kidney stones and the side effects of the drugs cannot be avoided. Increasing incidence of the stone formation associated with inflammation and severe pain, the demand of polyherbal formulations have gained more attention in preventing a suffering from lithiasis. The various herbal plants extract consist of active phytoconstituents like flavonoids, alkaloids, saponins, strerols possesses an bioactivity like diuretic, ant-inflammatory, analgesic and anti-oxidant property. The current review emphasizes the understanding pathology of the stone formation and traditional used medicinal plants as an alternative complementary therapy with less side effects. In addition, the review has also put an effort to summarize mechanisms of various herbal plants in the management of urolithiasis and providing a future investments and direction in developing plant based formulations for urolithiasis.
Allopurinol, a first line urate-lowering therapy, has been associated with serious cutaneous reactions that have a high mortality. A number of risk factors for these serious adverse reactions have been identified including ethnicity, HLA-B∗5801 genotype, kidney impairment, allopurinol starting dose, and concomitant diuretic use. There is a complex interplay between these risk factors, which may (albeit rarely) lead to allopurinol-related serious adverse events. Although oxypurinol, the active metabolite of allopurinol, has been implicated, there is no defined drug concentration at which the reaction will occur. There is no specific treatment other than the cessation of allopurinol and supportive care. Whether hemodialysis, which rapidly removes oxypurinol, improves outcomes remains to be determined. Strategies to help reduce this risk are therefore important, which includes screening for HLA-B∗5801 in high-risk individuals, commencing allopurinol at low dose, and educating patients about the signs and symptoms of severe cutaneous adverse reactions, and what to do if they occur.
Fibrogenesis is a common feature for all types of chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the main processes involving renal fibrosis and its inhibition is considered as a preventive/therapeutic strategy for CKD. Trigonelline (TRIG), a plant alkaloid commonly found in herbs, coffee bean, soy bean and other edible food plants, has several beneficial effects on human health and has been proposed to reduce renal fibrosis but with unclear mechanisms. This study thus addressed cellular mechanism underlying the anti-fibrogenic effects of TRIG in renal tubular epithelial cells grown in vitro. EMT was successfully induced by oxalate treatment as indicated by morphological changes into spindle-shape cells, increased expression of mesenchymal proteins (fibronectin, vimentin and α-smooth muscle actin (α-SMA)), decreased expression of epithelial proteins (E-cadherin and zonula occludens-1 (ZO-1)) and increased activity of a profibrotic factor (matrix metalloproteinase-9 (MMP-9)). Interestingly, these oxalate-induced EMT features could be attenuated by TRIG pretreatment. Moreover, TRIG also prevented oxalate-induced cell migration, reactive oxygen species (ROS) overproduction, and down-regulation of Nrf-2 signaling molecule. These data indicated that TRIG could attenuate the effects of oxalate-induced EMT and thus may serve as the anti-fibrotic compound for prevention and/or treatment of CKD.
Introduction:
Changes in the surgical treatment of nephrolithiasis, owing to recent technical advances and innovations, have made treatments more effective and less invasive. In this retrospective, observational cohort study, we identified the changing trends in the treatment of nephrolithiasis.
Materials and methods:
We included patients with newly diagnosed nephrolithiasis who received any treatment in the United States, including extracorporeal shockwave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), and open surgery, from January 2007 to December 2014. Demographic factors, such as age, sex, region, surgical treatment type, and cost data, were analyzed.
Results:
The median age of patients at treatment was 52 years, and the ratio of men and women was similar. There were definite changes in the trends of all treatment modalities (p < 0.01). Both the number and percentage tended to increase for RIRS, whereas for SWL, the number increased, but the percentage showed a steady decrease. In PCNL, both number and percentage increased to a minor degree. The overall cost of nephrolithiasis treatments during the study period nearly doubled (from $30,998,726 to $57,310,956). The number of treatments and average cost per treatment increased annually for each treatment modality. RIRS was the least expensive; the other procedures in decreasing order of their mean costs were as follows: SWL, PCNL, and open surgery.
Conclusions:
There was a gradual but constant change in treatment trends of nephrolithiasis, with an increasing trend for RIRS and a decreasing trend for SWL. Although PCNL has relatively invasive characteristics, it is still in steady demand.
Objective:
To evaluate the protective effects of melatonin (Mel) on an ethylene glycol-induced nephrolithiasis model in rats.
Methods:
Thirty-two Wistar albino rats were divided into 4 groups; control, ethylene glycol (EG), melatonin prevention (Mel+EG+Mel), melatonin treatment (EG+Mel) groups. 0.75% EG was added to drinking water to create nephrolithiasis model. EG group received EG and Mel+EG+Mel group received both EG and melatonin for 8 weeks. In EG+Mel group, EG is given for 8 weeks and melatonin is given for the last 4 weeks of the experiment. At the end of experimental period, urine, blood samples and tissues were collected.
Results:
In 24-hour urine samples, calcium, citrate and creatinine levels were decreased and oxalate levels were increased in EG group whereas Mel prevention and Mel treatment reversed these parameters back to control levels. Malondealdehyde, glutathione activities, myeloperoxidase, superoxide dismutase levels and caspase-3 activity showed improvements in melatonin treated groups when compared with EG group. 8-hydroxydeoxyguanosine, matrix metalloproteinase-9 levels, N-acetly-β-glucosaminidase activity and osteopontin mRNA expression were elevated in EG group and decreased back to control levels in Mel+EG+Mel and EG+Mel groups. Histological examination showed improvement in melatonin treated groups when compared with EG group.
Conclusion:
Melatonin can prevent crystalluria and kidney damage due to crystal formation and aggregation. Melatonin can be considered as a potential prophylactic and protective agent in high-risk patients for urinary stone formation or recurrence if supported by further clinical studies.
The objective of the present study was to investigate therapeutic efficacy of standardized fenugreek seed extract with trigonelline as marker (SFSE-T) in experimental urolithiasis in rats. Effects of subacute oral treatments of SFSE-T (30 and 60 mg/kg) and reference anti-urolithiasis drug, Cystone (750 mg/kg) were evaluated against 0.75% ethylene glycol (EG) and 1 % w/v ammonium chloride (AC) induced urolithiasis in rats. The biochemical (urinary and serum) and histopathological parameters were investigated. Subacute oral treatment of SFSE-T (60 mg/kg) showed reversal of EG+AC induced changes in urine (decreased 24-h urine output, pH, excretion of creatinine, citrate, and chloride and increased uric acid and oxalate excretion) and serum (increased creatine, uric acid and blood urea nitrogen) parameters and decreased creatine clearance. Histopathology examination of the kidneys sections from SFSE-T (60 mg/kg) treated rats showed lowered number of crystals, cell damage and tubulointerstitial damage index as compared with EG+AC control rats. Standardized fenugreek seed extracts showed promising therapeutic effect against experimental urolithiasis in rats.
Cisplatin is one of the extensively used anticancer drugs against various cancers. Dosage dependent nephrotoxicity is the major problem in cisplatin chemotherapy. Cisplatin induced nephrotoxicity results in the depletion of renal antioxidant defence system. Our present study is aimed to investigate the nephroprotective effect of vanilic acid to against cisplatin induced nephrotoxicity in male wistar rats. Elevated levels of serum creatinine, blood urea nitrogen, serum uric acid and reduced antioxidant status were observed as indicatives of nephrotoxicity in cisplatin (7 mg/kg bw) alone administered rats. Animals which are pre-treated with vanillic acid (50 mg/kg and 100 mg/kg) restored the elevated levels of renal function markers and reduced antioxidant status to near normalcy when compared to cisplatin alone treated animals. Cisplatin induced lipid peroxidation was markedly reduced by oral administration of vanillic acid at a high dose. The findings in the present study suggest that vanillic acid is a potential antioxidant that reduce cisplatin nephrotoxicity and can be as a combinatorial regimen in cancer chemotherapy.
Infectious urolithiasis is a consequence of persistent urinary tract infections caused by urease producing bacteria e.g. Proteus mirabilis. These stones are composed of struvite and carbonate apatite. Their rapid growth and high recurrence indicate that so far appropriate methods of treatment have not been found. In the present study, the inhibitory effect of phenolic compounds was investigated in vitro against formation of struvite/apatite crystals. The impact of these substances with different chemical structures on crystallization caused by clinical isolates of P. mirabilis was tested spectrophotometrically using a microdilution method. Among the 11 tested compounds resveratrol, epigallocatechin gallate, peralgonidin, vanillic and coffee acids at the concentrations 250-1000μg/ml inhibited P. mirabilis urease activity and crystallization. However, only vanillic acid had such an effect on all tested strains of P. mirabilis. Therefore, using an in vitro model, bacterial growth, crystallization, urease activity and pH were examined for 24h in synthetic urine with vanillic acid. Effect of vanillic acid was compared with that of other known struvite/apatite crystallization inhibitors (acetohydroxamic acid, pyrophosphate) and it was shown that vanillic acid strongly inhibited bacterial growth and the formation of crystals. It can be assumed that this compound, after further studies, can be used in the treatment or prophylaxis of infectious urolithiasis.
Under suitable conditions, oxalic acid and indole react to form a red- or pink-colored compound which conforms to Beer's law. Photometric comparison with standards permits the determination of oxalic acid in concentrations as low as 0.030 mg. per ml. The method is simple and possesses a high degree of sensitivity, the average being within ±2%.
Boerhaavia diffusa Linn. (Nyctaginaceae) is widely used in traditional Indian medicines against renal afflictions including calcium oxalate (CaOx) urolithiasis and is known for antioxidant activity.
The present study was designed to investigate the ameliorating effect of aqueous extract of B. diffusa roots (BDE) in hyperoxaluric oxidative stress and renal cell injury.
In vitro antioxidant activity of BDE was estimated in terms of total phenolic content and 1,1-diphenyl-2-picryl hydrazyl free radical scavenging activity. Wistar albino rats were given 0.75% v/v ethylene glycol in drinking water to induce chronic hyperoxaluria and simultaneously BDE was given to nephrolithiasic treated rats at the dose of 100 and 200 mg/kg b.w. orally for 28 days. Urinary volume, oxalate, serum creatinine, blood urea nitrogen (BUN), malondialdehyde (MDA) and antioxidant enzyme (SOD, CAT, GST, GPx) were evaluated.
BDE extract was found to posses a high total phenolic content and exhibited significant free radicals scavenging activity. Oxalate excretion significantly increased in hyperoxaluric animals as compared to control which was protected in BDE-treated animals. BDE treatment significantly reduced level of MDA and improved the activity of antioxidant enzymes followed by reduction in BUN and serum creatinine. In addition, BDE reduced the number of CaOx monohydrate crystals in the urine. Histological analysis depicted that BDE treatment inhibited deposition of CaOx crystal and renal cell damage.
The present study reveals that antioxidant activity of BDE significantly protects against hyperoxaluric oxidative stress and renal cell injury in urolithiasis.