A Sodium Oxalate-Rich Diet Induces Chronic Kidney Disease and Cardiac Dysfunction in Rats.

Chronic kidney disease (CKD) is a worldwide public health issue affecting 14% of the general population. However, research focusing on CKD mechanisms/treatment is limited because of a lack of animal models recapitulating the disease physiopathology, including its complications. We analyzed the effects of a three-week diet rich in sodium oxalate (OXA diet) on rats and showed that, compared to controls, rats developed a stable CKD with a 60% reduction in glomerular filtration rate, elevated blood urea levels and proteinuria. Histological analyses revealed massive cortical disorganization, tubular atrophy and fibrosis. Males and females were sensitive to the OXA diet, but decreasing the diet period to one week led to GFR significance but not stable diminution. Rats treated with the OXA diet also displayed classical CKD complications such as elevated blood pressure and reduced hematocrit. Functional cardiac analyses revealed that the OXA diet triggered significant cardiac dysfunction. Altogether, our results showed the feasibility of using a convenient and non-invasive strategy to induce CKD and its classical systemic complications in rats. This model, which avoids kidney mass loss or acute toxicity, has strong potential for research into CKD mechanisms and novel therapies, which could protect and postpone the use of dialysis or transplantation.

In-office Treatments for Dentin Hypersensitivity: A Randomized Split-mouth Clinical Trial.

PURPOSE: To assess the effectiveness of four in-office therapies used for the treatment of dentin hypersensitiviy (DH) after one single application. MATERIALS AND METHODS: A randomised, controlled, split-mouth clinical trial was designed to evaluate the following treatments: 5% sodium fluoride varnish (positive control); 3% potassium oxalate; two-step self-etching adhesive; high power diode laser. Nineteen patients were selected and one tooth per quadrant was included in the study. After evaporative stimulation, pain was quantified by the Visual Analog Scale (VAS) at baseline, immediately after treatment, and after 15, 30 and 60 days. RESULTS: Compared to the baseline values, fluoride varnish (p = 0.00) and potassium oxalate (p = 0.00) presented an immediate desensitising effect that remained constant at 15, 30 and 60 days. The high-power diode laser presented significant reduction in VAS scores after 15 days (p = 0.00), while in the self-etching adhesive group, a significant reduction in VAS scores was observed only after 60 days (p = 0.03). The change in VAS ([VAS x days] - VAS baseline) differed among the groups immediately after treatment, being higher in the fluoride varnish and lower in the adhesive groups, but no statistically significant difference was found at time intervals of 15, 30 and 60 days. CONCLUSION: When an immediate desensitising effect is desired after one single application, fluoride varnish and potassium oxalate should be used. High-power diode laser and self-etching adhesive may not be clinically considered an appropriate desensitising therapy after one single application.

Oral administration of oxalate-enriched spinach extract as an improved methodology for the induction of dietary hyperoxaluric nephrocalcinosis in experimental rats.

Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, this study is aimed to develop an improved model for the induction of dietary hyperoxaluria, and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups. Group I, control; group II rats received 0.75% EG, group III rats fed with 5% KOx diet and group IV and V rats were administered with spinach extract of 250 and 500 mg soluble oxalate/day respectively, for 28 d. Urine and serum biochemistry were analyzed. After the experimental period, rats were sacrificed, liver and kidney tissue homogenates were used for antioxidant and lipid peroxidation assay. Relative change in expression of kidney injury molecule-1 (KIM-1) and crystal modulators genes in kidney tissues were evaluated. Tissue damage was assessed by histology studies of liver and kidney. Experimental group rats developed hyperoxaluria and crystalluria. Urine parameters, serum biochemistry, antioxidant profile, lipid peroxidation levels and gene expression analysis of experimental group II and III rats reflected acute kidney damage compared to group V rats. Histopathology results showed moderate hyperplasia in liver and severe interstitial inflammation in kidneys of group II and III than group V rats. Ingestion of naturally available oxalate enriched spinach extract successfully induced dietary hyperoxaluria and nephrocalcinosis in rats with minimal kidney damage.

Dietary recommendations and treatment of patients with recurrent idiopathic calcium stone disease.

This review describes the various dietary regimens that have been used to advise patients on how to prevent the recurrence of their calcium-containing kidney stones. The conclusion is that although there is some general advice that may be useful to many patients, it is more efficacious to screen each patient individually to identify his/her main urinary, metabolic, nutritional, environmental, and lifestyle risk factors for stone-formation and then tailor specific advice for that particular patient based on the findings from these investigations. If the patient can be motivated to adhere strictly to this conservative approach to the prophylactic management of their stone problem over a long time period, then it is possible to prevent them from forming further stones. This approach to stone management is considerably less expensive than any of the procedures currently available for stone removal or disintegration. In the UK, for each new stone episode prevented by this conservative approach to prophylaxis it is calculated to save the Health Authority concerned around £2000 for every patient treated successfully. In the long term, this accumulates to a major saving within each hospital budget if most stone patients can be prevented from forming further stones and when the savings are totalled up country-wide saves the National Exchequer considerable sums in unclaimed Sick Pay and industry a significant number of manpower days which would otherwise be lost from work. It is also of immense relief and benefit to the patients not to have to suffer the discomfort and inconvenience of further stone episodes.

Oxamate-mediated inhibition of lactate dehydrogenase induces protective autophagy in gastric cancer cells: involvement of the Akt-mTOR signaling pathway.

Cancer cells produce a substantial amount of energy through aerobic glycolysis even in the presence of adequate oxygen. Lactate dehydrogenase (LDH), a key regulator of glycolysis, reversibly catalyzes the conversion of pyruvate to lactate. Recently, oxamate, an inhibitor of LDH, has been shown to be a promising anticancer agent. However, the detailed mechanism remains largely unclear. In this study, we demonstrate that oxamate inhibits the viability of human gastric cancer cells in a dose- and time-dependent manner. In addition, treatment with oxamate induces protective autophagy in gastric cancer cells. Moreover, autophagy inhibited by chloroquine or Beclin 1 small interfering RNA (siRNA) enhances oxamate-induced apoptosis and proliferation inhibition. Further study has shown that oxamate treatment significantly augments reactive oxygen species (ROS) production. Furthermore, cells pretreated with N-acetyl cysteine (NAC), a ROS inhibitor, display significantly reduced ROS production and attenuated oxamate-induced autophagy. Finally, functional studies reveal that the Akt-mTOR signaling pathway, a major negative regulator of autophagy, is inhibited by oxamate. Together, our results provide new insights regarding the biological and anti-proliferative activities of oxamate against gastric cancer, and may offer a promising therapeutic strategy for gastric cancer.

Evaluation of potassium binoxalate gel and Nd:YAG laser in the management of dentinal hypersensitivity: a split-mouth clinical and ESEM study.

Dentinal hypersensitivity is one of the oldest recorded complaints of discomfort to mankind and yet there appears to be no permanent treatment for this clinical condition. This study was designed to evaluate the clinical efficacy of potassium binoxalate gel and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser on dentin hypersensitivity for a period of 9 months. Eighty teeth (20 subjects, 25-55 years old, M = F) were evaluated in a split-mouth design to receive potassium binoxalate (group A, 40 teeth) and Nd:YAG (group B, 40 teeth: 1 W, 10 Hz, and 60 s, irradiated twice). The diameter of output beam was about 300 µm with a distance of 2 mm between laser fiber or tip and tooth surface. The clinical efficacy was evaluated by air-blast test and cold-water test using visual analog scale. Electron microscopy photomicrographs were taken to confirm the results. Analysis was done at baseline; immediately post-treatment; and at 3, 6, 9 months post-treatment. Student's paired and unpaired T tests were used to evaluate the statistical analysis. Both treatment modalities were effective in reducing dentine hypersensitivity. However, Nd:YAG laser was better when intragroup comparison was made at 9 months post-treatment. Nd:YAG lasers is better in long-term treatment (up to 9 months) owing to the melting of dentinal tubules. However, due to depth of penetration of microcrystals, gel was better when ease of the procedure is considered. Nevertheless, both treatment modalities resulted in recurrence. Hence, further studies are needed to discover an agent, which can be considered as a "gold standard".

Effectiveness of a desensitizing agent for topical and home use for dentin hypersensitivity: a randomized clinical trial.

PURPOSE: To evaluate the effectiveness of a desensitizing gel for topical and home use for the treatment of dentin hypersensitivity (DH) by means of a 3-arm parallel, randomized, double blind clinical trial. METHODS: 107 participants were allocated to three groups: placebo gel (PG), test gel (TG) (5% sodium fluoride, 5% potassium oxalate, 10% strontium chloride) and 2% sodium fluoride gel (FG). DH measurement was performed by a single blind examiner by means of the visual analog scale (VAS) after tactile (blunt tipped probe), thermal (air blast) and osmotic (water blast) stimulus at time intervals of baseline, 7, 15 and 30 days. RESULTS: The greatest reductions in DH were observed for the TG, with significant differences for FG in the thermal (Δ = -56 vs -30) and osmotic stimuli (Δ = -44 vs -18). Considering the percentage of participants with moderate/severe pain at 30 days, the TG demonstrated the lowest percentages, with significant differences in comparison with the other groups in thermal and osmotic stimuli. We can conclude that the test gel showed a greater reduction in DH than fluoride 2% and placebo gel, and maybe a treatment option for individuals with DH.

Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and therapy of ischemia-reperfusion injury.

The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the generation of high level of hydrogen peroxide (H2O2). In this study, we report a novel diagnostic and therapeutic strategy for I/R injury based on H2O2-activatable copolyoxalate nanoparticles using a murine model of hind limb I/R injury. The nanoparticles are composed of hydroxybenzyl alcohol (HBA)-incorporating copolyoxalate (HPOX) that, in the presence of H2O2, degrades completely into three known and safe compounds, cyclohexanedimethanol, HBA and CO2. HPOX effectively scavenges H2O2 in a dose-dependent manner and hydrolyzes to release HBA which exerts intrinsic antioxidant and anti-inflammatory activities both in vitro and in vivo models of hind limb I/R. HPOX nanoparticles loaded with fluorophore effectively and robustly image H2O2 generated in hind limb I/R injury, demonstrating their potential for bioimaging of H2O2-associated diseases. Furthermore, HPOX nanoparticles loaded with anti-apoptotic drug effectively release the drug payload after I/R injury, exhibiting their effectiveness for a targeted drug delivery system for I/R injury. We anticipate that multifunctional HPOX nanoparticles have great potential as H2O2 imaging agents, therapeutics and drug delivery systems for H2O2-associated diseases.

Impact of oxalic acid on rumen function and bacterial community in sheep.

Oxalic acid (OA) is a secondary compound occurring in a wide range of plants consumed by ruminants, especially in saline lands or in arid and semi-arid regions. However, its impact on the rumen microbial community and its changes over time, as well as the potential consequences on ruminal function, remain unknown. To examine this impact, five ewes fitted with a ruminal cannula and fed low-quality grass hay were dosed daily with 0.6 mmol of OA/kg body weight through the cannula for 14 days. On days 0 (before the start), 4, 7 and 14 of the administration period, samples of ruminal digesta were collected throughout the day (0, 3, 6 and 9 h after the morning feeding) for analysis of the bacterial community and fermentation parameters (pH, ammonia and volatile fatty acid (VFA) concentrations). In addition, two feedstuffs were incubated in situ using the nylon bag technique to estimate ruminal degradation. Terminal restriction fragment length polymorphism was employed to monitor the dynamics of total bacteria, and quantitative real-time PCR was used to investigate the abundance of the oxalate-degrading Oxalobacter formigenes. Neither pH nor total VFA concentrations were affected. Nevertheless, OA dosing altered molar proportions of most individual VFA and ammonia concentrations (P < 0.001). The dry matter disappearance of alfalfa hay was reduced on days 7 and 14 and that of barley straw only on day 7 (P < 0.01). These slight changes were related to others observed in the relative frequency of a number of terminal restriction fragments. Variations in the ruminal microbiota occurred rapidly with OA administration, which did not modify the bacterial diversity significantly but altered the structure of the community. However, many of these changes were reversed by the end of the experiment, with no significant differences between days 0 and 14 of dosing. These results suggest a rapid adaptation of the rumen bacterial community linked to the estimated increase in the abundance of O. formigenes (from 0.002% to 0.007% of oxc gene in relation to the total bacteria 16S rDNA; P < 0.01), which is assumed to be responsible for oxalate breakdown.

Postharvest treatments with salicylic acid, acetylsalicylic acid or oxalic acid delayed ripening and enhanced bioactive compounds and antioxidant capacity in sweet cherry.

Sweet cherry cultivars ('Cristalina' and 'Prime Giant') harvested at commercial ripening stage were treated with salicylic acid (SA), acetylsalicylic acid (ASA) or oxalic acid (OA) at 1 mM and then stored for 20 days under cold temperature. Results showed that all treatments delayed the postharvest ripening process, manifested by lower acidity, color changes and firmness losses, and maintained quality attributes for longer periods than controls. In addition, total phenolics, anthocyanins and antioxidant activity increased in untreated fruit during the first 10 days of storage and then decreased, while in fruits of all treatments, these parameters increased continuously during storage without significant differences among treatments. Thus, postharvest treatments with natural compounds, such as SA, ASA or OA, could be innovative tools to extend the storability of sweet cherry with higher content of bioactive compounds and antioxidant activity as compared with control fruits.

Improved methodology to induce hyperoxaluria without treatment using hydroxyproline.

The use of hydroxyproline (HP) to generate hyperoxaluria in the rat is a problem because it is impossible to separate the effect of oxalate on renal injury from the effects of HP and the large array of metabolic intermediates formed when HP is converted to oxalate. Previously, the Dahl salt-sensitive (SS) and Brown Norway (BN) rat strains were studied to determine genetic control of resistance or susceptibility to HP-induced renal injury and crystal deposition. To develop a better model to induce hyperoxaluria without causing injury from HP metabolites, animals were fed a diet containing various levels of added oxalate (0, 1, 2, 3, or 5%). After 5 weeks rats were killed and the kidneys were removed for microscopic evaluation of tubule changes and crystal deposition. The 3 and 5% oxalate-fed groups had a substantial increase in urine oxalate, about 50 and 140 µmol/g body weight over controls, respectively. Both the SS and BN 3% oxalate-fed animals showed only slightly elevated tubule area and no crystal deposition. However, BN animals fed 5% oxalate had a dramatic increase in their percent tubule areas compared to control BN rats and treated SS rats. Crystal deposition in the kidneys was only observed in the 5% oxalate-fed groups. The BN kidneys demonstrated a threefold higher crystal deposition compared to oxalate-fed SS rats. We conclude that oxalate-supplemented food is a better method of producing hyperoxaluria in the rat than using HP which may introduce metabolic intermediates injurious to the kidney.

A study of calcium intake and sources of calcium in adolescent boys and girls from two socioeconomic strata, in Pune, India.

Adequate intake of calcium is important for skeletal growth. Low calcium intake during childhood and adolescence may lead to decreased bone mass accrual thereby increasing the risk of osteoporotic fractures. Our aim was to study dietary calcium intake and sources of calcium in adolescents from lower and upper economic strata in Pune, India. We hypothesized that children from lower economic strata would have lower intakes of calcium, which would predominantly be derived from non-dairy sources. Two hundred male and female adolescents, from lower and upper economic stratum were studied. Semiquantitative food frequency questionnaire was used to evaluate intakes of calcium, phosphorus, oxalic acid, phytin, energy and protein. The median calcium intake was significantly different in all four groups, with maximum intake in the upper economic strata boys (893 mg, 689-1295) and lowest intake in lower economic strata girls (506 mg, 380-674). The median calcium intake in lower economic strata boys was 767 mg (585-1043) and that in upper economic strata girls was 764 mg (541-959). The main source of calcium was dairy products in upper economic strata adolescents while it was dark green leafy vegetables in lower economic strata adolescents. The median calcium intake was much lower in lower economic strata than in the upper economic strata both in boys and girls. Girls from both groups had less access to dairy products as compared to boys. Measures need to be taken to rectify low calcium intake in lower economic strata adolescents and to address gender inequality in distribution of dairy products in India.

Antioxidant and anti-inflammatory activities of hydroxybenzyl alcohol releasing biodegradable polyoxalate nanoparticles.

p-Hydroxybenzyl alcohol (HBA) is one of phenolic compounds in herbal agents and plays a pivotal role in protection against oxidative damage-related diseases due to anti-inflammatory effects. We have developed a new biodegradable and anti-inflammatory peroxalate copolymer in which HBA is chemically incorporated into its backbone. The HBA-incorporated copolyoxalate (HPOX) was synthesized from a condensation reaction of oxalyl chloride, 1,4-cyclohexamethanol and HBA and was capable of releasing pharmaceutically active HBA during hydrolytic degradation. HPOX could be dispersed into a single emulsion for the formulation of nanoparticles which had a mean size approximately 500 nm in diameter. The nanoparticles released HBA which was able to inhibit the production of nitric oxide (NO) by suppressing the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. HPOX nanoparticles also reduced the production of tumor necrosis factor-alpha (TNF-alpha). The remarkable features of HPOX are that the polymer degrades completely into small molecules and one of degradation products is a pharmaceutically active compound. We anticipate that HPOX is highly potent and versatile for the treatment of inflammatory diseases.

Increased protein intake on controlled oxalate diets does not increase urinary oxalate excretion.

High animal protein intake is a risk factor for calcium oxalate stone disease. The effect of dietary protein on the urinary excretion of calcium, acid and citrate is well established. However, its effect on oxalate excretion is unclear, due in part to an inadequate control of dietary oxalate intake in previous studies. This relationship warrants clarification due to the proposed important role of the metabolism of amino acids in endogenous oxalate synthesis. In this study, 11 normal subjects consumed controlled oxalate diets containing 0.6, 1.2 and 1.8 g protein/kg body weight/day. The analysis of 24 h urine collections confirmed that as protein intake increased, urinary calcium and glycolate increased and urinary pH and citrate decreased. The increased glycolate excretion was due in part to an increased hydroxyproline, but not glycolate consumption. Total daily urinary oxalate excretion did not change. When indexed to creatinine there was a small but significant decrease in oxalate excretion. This is most likely due to hyperfiltration. These results indicate that as dietary protein intake increases, the catabolism of diet-derived amino acids is not associated with an increased endogenous oxalate synthesis in normal subjects.

An evaluation of the acceptability as forage of some nutritive and antinutritive components and of the dry matter degradation profiles of five species of Ficus.

The suitability of five species of Ficus, F. mucoso, F. thonningii, F. polita, F. religiosa and F. benjamina, for feeding ruminant livestock was studied. The nutritive and antinutritive components were determined and the acceptability of the forages to livestock was assessed using a cafeteria method in 8 adult small ruminants. Also, the degradation potential of the dry matter of the five Ficus species was investigated using 3 fistulated sheep. The crude protein (CP) content of the Ficus species varied significantly (p < 0.05), ranging from 130 to 180 g/kg DM. The content of neutral detergent fibre (NDF) also varied significantly (p < 0.05), ranging from 650 to 710 g/kg DM. The organic matter (OM) contents did not differ significantly (p > 0.05), having a mean value of 916 g/kg DM. The concentrations of tannin, saponin, phytic acid and oxalic acid were low. The acceptability of the forage was similar for four of the species but poor for F. polita. The extent of DM degradation varied significant among the Ficus species, the ranking order being F. benjamina > F. thonningii > F. mucoso > F. religiosa > F. polita.

Urinary oxalic acid excretion differs after oral loading of rats with various oxalate salts.

BACKGROUND: To compare urinary oxalate excretion after the oral administration of oxalic acid, disodium oxalate, or calcium oxalate in rats. METHODS: Male Wistar rats were divided into four groups of six rats each and were intravenously hydrated with normal saline, and then were administered normal saline (control group), 10 mg of oxalic acid, equimolar disodium oxalate, or equimolar calcium oxalate via a gastrostomy. Urine specimens were collected just before administration and at hourly intervals up to 5 h afterwards. The urinary oxalate, calcium, magnesium and phosphorus levels were measured. RESULTS: Urinary oxalate excretion peaked at 1-2 h after administration of oxalic acid or equimolar disodium oxalate, while administration of calcium oxalate only caused a small increase of urinary oxalate excretion. Cumulative urinary oxalate excretion during 5 h was 1.69 +/- 0.10 mg (mean +/- SD; 17%), 1.43 +/- 0.13 mg (13%), and 0.22 +/- 0.03 mg (2%) after the administration of oxalic acid, disodium oxalate, and calcium oxalate, respectively. Urinary calcium excretion showed a decrease in the oxalic acid and disodium oxalate groups, while urinary magnesium or phosphorus excretion did not change significantly. CONCLUSION: The upper gastrointestinal tract seems to be the major site of oxalic acid absorption and only free oxalate is absorbed irrespective of whether it is the sodium salt or not. After binding to calcium in the gut, oxalic acid absorption seems to be inhibited in the presence of calcium and this means that calcium oxalate is poorly absorbed (at least in the upper gastrointestinal tract).

The control of Varroa destructor using oxalic acid.

Twenty-four honeybee (Apis mellifera) colonies were used to monitor the efficacy of a solution of 2.9% oxalic acid (OA) and 31.9% sugar against the mite Varroa destructor. Mite mortality was established prior to and after OA treatments, which were conducted in August and September. The treatments resulted in 37% mite mortality as opposed to 1.11% in the controls. OA treatment conducted in September on previously untreated colonies resulted in 25% mite mortality. OA treatments in October and November resulted in approximately 97% mite mortality. These results suggest that OA is effective during the broodless period and less effective when applied to colonies with capped broods. The possible use of OA against the Varroa mite in honeybee colonies as an alternative to routine chemical treatments is discussed.

Prevention of nephrolithiasis.

The high incidence of recurrence after an initial stone event underscores the need for an effective medical prophylactic program. Dietary modification and drug therapies have long been advocated to reduce the likelihood of stone recurrence. While the efficacy of a high fluid intake has been validated in a randomized trial, the benefit of other dietary measures is based on modulation of urinary stone risk factors and outcomes derived from observational studies. Several drug therapies have been evaluated in a limited number of prospective, randomized trials and efficacy has been demonstrated for thiazides, allopurinol and alkali citrate in some populations of recurrent stone formers. The role of selective versus nonselective therapy for stone prevention awaits further study.

Should dietary calcium and protein be restricted in patients with nephrolithiasis?

Renal stone disease is a painful condition that affects 1-20% of the general population. Therapy aimed at decreasing the incidence of recurrent stones includes dietary advice. Dietary considerations include intake of both calcium and protein. Calcium restriction in stone formers is not recommended because it can have adverse effects on bone and the incidence of stones. Although a high-protein diet can elevate urinary calcium, uric acid, and sulfate and decrease urinary citrate, which may alter the propensity to form stones, restriction of protein to less than the current RDA for the management of stone disease can not be recommended at this time.

[Hypocalcemia in a four-week-old foal]. / Hypocalcemie bij een vier weken oud veulen.

Intake of Rumex, a plant genus of the Polygonaceae family, probably led through the assimilation of oxalic acid, to hypocalcaemia in a four-week old foal. This foal was presented with muscle rigidity and a stiff gait. Both the total and ionized calcium concentrations were low, 1.38 mmol/l and 0.54 mmol/l respectively. The foal was treated with a total of 150 ml of a 20% calcium solution IV. The foals neuromuscular signs resolved within a few hours after receiving calcium solution.