Oxalate Crystals Research Articles

Nanonization of ethanolic tulsi leaf extract and its major compound eugenol and evaluation of their inhibitory potential against calcium oxalate crystal (a kidney stone component)

Nanonization of ethanolic tulsi leaf extract and its major compound eugenol and evaluation of their inhibitory potential against calcium oxalate crystal (a kidney stone component)

Crystal growth of calcium oxalate mono- and dihydrate under laminar flow in microfluidic devices

Crystallization of calcium oxalate (CaOx) was studied in microfluidic devices, with geometries simulating kidney stones collecting ducts, under laminar flow conditions relevant for kidney stone formation.

Luteolin alleviated calcium oxalate crystal induced kidney injury by inhibiting Nr4a1-mediated ferroptosis

BackgroundThe global incidence of calcium oxalate (CaOx) kidney stones is rising, and effective treatments remain limited. Luteolin (Lut), a naturally flavonoid present in several plants, is recognized for its anti-inflammatory, anti-injury, and neuroprotective effects. However, its effects on CaOx kidney stone formation and the associated kidney damage are still unknown. ObjectiveOur study seeks to explore the therapeutic impact of Lut on kidney injury and renal fibrosis caused by CaOx crystal and to elucidate the underlying mechanisms. MethodsCaOx stone models were established in mice via intraperitoneal injection of glyoxylate (Gly, 100 mg/kg) for 12 days. Lut (50 mg/kg or 100 mg/kg) was administered intraperitoneally 7 days before and with the period of Gly treatment. Kidney function and histopathology changes in renal tissues were assessed. RNA sequencing was used to explore potential mechanisms between the model and Lut treatment groups. Molecular docking simulations evaluated the interaction between Lut and the downstream target Nr4a1. Moreover, Nr4a1 knockout mice and knockdown plasmids were used to validate the mechanism of Lut in the treatment of CaOx crystal-induced kidney injury. ResultsLut significantly mitigated kidney injury and renal fibrosis induced by CaOx crystal, as evidenced by improved kidney function, histopathology staining and Western blot analysis. Lut treatment also significantly inhibited lipid peroxidation and mitochondrial injury. In vitro experiments further demonstrated that Lut treatment alleviated injury and fibrosis in HK-2 cells. Mechanistically, RNA sequencing and molecular docking simulations indicated that Lut binds to Nr4a1 to regulate ferroptosis, thereby alleviating kidney injury induced by CaOx crystal. Overexpression of Nr4a1 negated Lut's beneficial effects, whereas Nr4a1 knockout exhibited a protective effect against kidney injury. ConclusionLut exerts its protective effects by inhibiting ferroptosis via targeting Nr4a1-Slc7a11-GPX4 pathway, alleviating kidney injury and renal fibrosis caused by CaOx crystal deposition.

Leaf yield quality of Swiss chard Beta vulgaris spp. cicla as influenced by ammonium: nitrate Ratio and Organic Fertilizer

The experiment was conducted to study the effect of NH4+:NO3- ratio and spraying with seaweed extract on the quality indicators of Swiss chard. Nitrate or ammonium fertilization was used alone at a concentration of 400 mg. L-1, or a balanced combination of both at a ratio of 200:200 mg L-1 in combination with spraying with SWE extract at levels of 0, 3, 6 g L-1. Generally, the results showed that the studied quality indicators were affected differently by different fertilization levels and combinations. As, the results showed that the interaction of NH4+:NO3- ratio (200:200) and seaweed extract at a concentration of 6 g L-1 led to the highest significant increase in leaf content of ascorbic acid to 44.92 mg 100 g-1 fresh weight and protein to 6.62%. However, other qualitative indicators, leaf content of oxalic acid 87.85 mg/100 g-1, oxalic acid/calcium ratio 1.73, and number of calcium oxalate crystals 265.13 crystals, recorded the highest values in the nitrate 400: 0 ammonium treatment in combination with the presence of SWE at a concentration of 3 g/L-1.

Stenotrophomonas strain DP30; a marine bacteria capable of precipitating calcium carbonate

This study aimed to evaluate the calcium carbonate precipitation potential of culturable bacteria found in sea surface water. Ureolytic strains were selected using Stuart’s broth. In the preliminary screening, strain DP30 was selected and used in further experiments. Based on the morphological, physiological, and biochemical characteristics with phylogenetic analysis of the 16S rRNA sequencing, the selected strain was identified as Stenotrophomonas maltophilia. DP30 showed the highest urease activity on the 7th day at 28 °C. In addition, it was found that the isolate can show urease activity in low pH environmental conditions such as pH 5. The strain DP30 precipitated CaCO3 on solid Urea-CaCl2 and B4 media but exhibited different crystal morphologies. Plate-like crystals appeared on solid Urea-CaCl2 media, while the strain produced dihydrate calcium oxalate and rhombohedral crystals on solid B4 media. EDS analysis confirmed that the precipitated minerals were composed solely of calcium, carbon, and oxygen. Furthermore, the study showed that S. maltophilia strain DP30 was able to precipitate calcium carbonate under aerobic conditions without urea hydrolysis. These findings suggest that the DP30 strain may have the potential for use in self-healing concrete applications. Moreover, calcium carbonate precipitation without urea hydrolysis where ammonia is produced will provide an environmentally friendly application.

Statistical Analysis of Microarray Data to Identify Key Gene Expression Patterns in Primary Hyperoxaluria

This study aims to utilize microarray data deposited by Romero et al. and conduct bioinformatic analysis for identifying differentially expressed genes (DEGs) associated with a novel method involving gene correction at the Alanine–Glyoxylate Aminotransferase (AGXT) locus and direct conversion of fibroblasts from primary hyperoxaluria type 1 (PH1) patients into healthy induced hepatocytes (iHeps) using Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR-associated protein 9 (CRISPR-Cas9) technology. Additionally, the study aims to elucidate the molecular mechanisms underlying hyperoxaluria compared to oxalate crystal formation. Romero et al.'s GSE226019 microarray data was retrieved from Gene Expression Omnibus. Statistical analysis was done in R and Bioconductor, utilizing rigorous methods to ensure robust and reproducible results. The limma program compared gene expression levels across groups. Pathway analysis, protein-protein interaction (PPI) network creation, and miRNA-target interaction network analysis were constructed. The top ten DEGs included ANGPTL3, SLC38A3, KNG1, BDH1, GC, ADH1C, ARG1, CYP3A4, AMBP, and CYP2C9. Enrichment analysis revealed significant associations with various biological pathways, including Linoleic acid metabolism and Retinol metabolism. Volcano plots and mean difference plots highlighted significant gene expression changes between different sample groups. Protein-protein interaction networks and miRNA-target interaction networks provided insights into molecular interactions and regulatory mechanisms. The top ten differentially expressed genes include ANGPTL3, SLC38A3, KNG1, BDH1, GC, ADH1C, ARG1, CYP3A4, AMBP, and CYP2C9—emerge as key players with strong associations to critical biological pathways like Linoleic acid metabolism and drug metabolism-cytochrome P450. Understanding the regulatory role of specific miRNAs (hsa-miR-4501, hsa-miR-5692c, hsa-miR-6731-3p, hsa-miR-6867-5p, hsa-miR-616-3p, hsa-miR-4468, hsa-miR-3692-3p, hsa-miR-4277, hsa-miR-4763-5p, hsa-miR-4797-5p) in gene expression could provide further insights into disease mechanisms and potential therapeutic avenues. The statistical findings provide a foundation for predictive modeling, hypothesis testing, and exploring personalized therapeutic strategies.

Prolyl hydroxylase domain inhibitors prevent kidney crystal formation by suppressing inflammation.

The early stages of kidney crystal formation involve inflammation and hypoxia-induced cell injury; however, the role of the hypoxic response in kidney crystal formation remains unclear. This study investigated the effects of a prolyl hydroxylase domain inhibitor (roxadustat) on renal calcium oxalate (CaOx) crystal formation through in vitro and in vivo approaches. In the in vitro experiment, murine renal tubular cells (RTCs) were exposed to varying roxadustat concentrations and CaOx crystals. CaOx monohydrate (COM) crystal adhesion was evaluated using fluorescent labels, whereas western blotting was used to examine protein expression. Quantitative real-time polymerase chain reaction was used to analyze gene expression changes. Macrophage responses were investigated by co-culturing them with RTCs treated with COM. In the in vivo experiment, C57BL/6J mice were injected with roxadustat or saline for 2days, followed by glyoxylate for 6days to induce renal crystal deposition. Biochemical measurements recorded plasma erythropoietin, urinary data, and pH levels. Roxadustat suppressed the adhesion of COM crystals to RTCs and the expression of proinflammatory genes, such as chemokine (C-C motif) ligand 2 (Ccl2) and secreted phosphoprotein 1 (Spp1). Roxadustat decreased the expression levels of Ccl2, tumor necrosis factor (Tnf), and interleukin6 (Il6) in co-cultured macrophages. In the in vivo experiment, the amount of renal CaOx crystal deposits was significantly lower in the roxadustat-treated group than in the vehicle group. Roxadustat treatment decreased Ccl2, Tnf, and adheision G protein-coupled receptor E1 (Adgre1) expression in the kidneys. Roxadustat reduced kidney inflammation and CaOx crystal deposition, suggesting its potential as a therapeutic option for kidney stone prevention.

Anatomical and Physicochemical Attributes of Endemic Medicinal Plant Species Vincetoxicum capparidifolium (Wight & Arn.) Kuntze, Apocynaceae

ABSTRACTVincetoxicum capparidifolium (Wight & Arn.) Kuntze [=Tylophora capparidifolia (Wight & Arn.) Kuntze], belonging to the family Apocynaceae, is a medicinal plant species endemic to the southern Western Ghats, Tamil Nadu, India. The current study sought to investigate the macroscopic, organoleptic, microscopic, physicochemical, and proximate compositional aspects of the fresh and powdered leaf and stem portions of V. capparidifolium. The anatomical peculiarities of the leaf parts reveal a hypostomatic nature with paracytic stomata, the epidermis being made up of thin‐walled cells covered with a thick cuticle (5.9 μm), and the hypodermis comprising angular collenchyma cells. The petiole is oval/rounded‐ellipse with abundant nonglandular multicellular trichomes ascending from the epidermis. The hypodermis is composed of collenchymatous cells containing many calcium oxalate crystals and silica bodies. Bicollateral vascular bundles with internal and external phloem characterize the leaf, stem, and petiole parts. The stem is covered by a thin cuticle, chlorenchymatous hypodermis, and large gelatinous fiber bundles (124.29 × 81.71 μm). Secondary growth in the stem is characterized by the development of periderm and lignified vascular tissues. Bicollateral vascular bundles are overlaid by irregular sclerenchyma patches (7.07 × 5.36 μm), a parenchymatous cortex, and pith composed of thin‐walled parenchyma cells. Scanning electron microscopic study of powdered plant parts disclosed the presence of fiber in the stem and a trace outline of leaf epidermal cells. X‐ray diffraction analysis specified indefinite crystallinity in the plant powder (57.038–69.500 nm). Thorough examination of pH, ash content, and percentage of crude lipid confirms that V. capparidifolium exhibits sufficient quality and purity.

Microscopic Evaluation and Qualitative Phytochemical Screening of Corchorus olitorius L. (Molokhia) Leaves

Corchrous is a genus which belongs to Tiliaceae family distributed across Asia and Africa. In the world, the Corchorus genus encompasses 75 taxa. Widely distributed across the tropics, Corchorus olitorius L. (Molokhia) is most likely found in every tropical African nation. Its use as a wild or farmed vegetable has been reported by numerous countries in tropical Africa. In Cyprus, this plant is used to prepare a dish after drying in the summer. The aim of this study was to investigate microscopic evaluation and phytochemical profile of the leaf extracts of C. olitorius. In microscopic evaluation experiments, powdered leaf part of the plant was examined under the microscope. For determination of phytochemical profile, some of secondary metabolites were determined qualitatively by chemical reactions. Microscopic analysis revealed that molokhia leaves displayed epidermis, stoma, calcium oxalate crystals, spongy parenchyma, glandular hair, trichome, midrib. The phytochemical profile identification of the leaf extracts of C. olitorius, revealed the presence of some active ingredients such as carbohydrates, cardioactives, and flavonoids.

DIAGNOSTIC INVESTIGATION OF AMERICAN ROBINS (TURDUS MIGRATORIUS) WITH FATAL ETHYLENE GLYCOL TOXICOSIS AND CONCURRENT PLASMODIUM SPP. INFECTION WITH RETROSPECTIVE REVIEW OF 44 YEARS OF DIAGNOSTIC DATA.

We describe a mortality event involving at least 44 adult American robins (Turdus migratorius) that were found dead on the morning of February 25, 2023 in a residential backyard in Natchitoches Parish, Louisiana. Five carcasses were submitted for diagnostic evaluation. All five robins were in good nutritional and feather condition with no external indicators of injury or illness. Grossly, kidneys were diffusely pale in all robins and 4/5 also had splenomegaly. Consistent histologic lesions included severe, multifocal to coalescing, renal tubular degeneration and necrosis with intraluminal, birefringent calcium oxalate crystals and calcified concretions. Toxicologic testing revealed a markedly elevated calcium concentration (10,000 parts per million) in a pooled kidney sample. Collectively, these findings support a diagnosis of ethylene glycol toxicosis. Ethylene glycol, an ingredient in antifreeze, is a hazardous toxicant in domestic and wild animals living in residential areas, although confirmed reports in songbirds are scarce. In the present case, the circumstances of ethylene glycol exposure are unknown but most likely anthropogenic in origin. Additionally, splenomegaly prompted molecular testing, which detected Plasmodium unalis in three robins and P. vaughani in one robin. Both Plasmodium spp. can infect a wide range of hosts, and although infections likely were subclinical, their detection raises awareness of their potential pathogenicity in wild birds. This mortality event underscores the need to recognize health risks posed by environmental contaminants and vector-borne pathogens to wildlife, and reinforces that wildlife, especially peridomestic species, can serve as sentinels for risks to domestic animal and human health.

A mouse model for the study of diet-induced changes in intestinal microbiome composition on renal calcium oxalate crystal formation.

Currently available animal models for calcium oxalate kidney stones are limited in their translational potential. Particularly with increasing interest in gut microbiota involvement in kidney stone disease, there are limited animal models which can be used. As such, we have developed a novel diet-induced hyperoxaluria murine model which addresses some of the shortcomings of other currently available models. Mice C57BL/6 mice were fed a 1.5% sodium oxalate supplemented chow for two weeks and showed no morbidity or mortality. Mice fed the sodium oxalate diet consistently had renal calcium oxalate crystal deposits as confirmed by polarized light microscopy, and energy-dispersive X-ray spectroscopy. We developed a isotope dilution high-performance liquid chromatography/mass spectrometry protocol which confirmed that our model produced both urinary and enteric hyperoxaluria. 16S ribosomal RNA sequencing of stool samples and cecal contents showed that sodium oxalate is a disruptor of the gut microbiome, and may interfere with commensal microbes in the gut microbiome. With consistent results this mouse model is superior to other models of kidney stone disease, as this model can be applied to investigate topics of oxalate absorption, transport, metabolism, excretion, crystal formation, the gut microbiome and testing of various therapeutic agents for translation to early stages of renal crystal formation in kidney stone disease.

Based on network pharmacology, the mechanism of Dioscin in alleviating renal tubular epithelial cell injury induced by calcium oxalate crystals was explored.

The commencement of kidney stone formation involves a crucial initial phase characterized by injury to renal tubular cells caused by calcium oxalate (CaOx). Dioscin (Dio) has been acknowledged for its potent anti-inflammation and anti-apoptotic properties; nevertheless, the impact and underlying Investigation into the molecular basis underlying the action of Dioscin in mitigating inflammation and apoptotic induced by exposure to calcium oxalate crystals in renal tissues remain unexplored.To comprehend the precise mechanism of Dioscin in the treatment of crystalline nephropathy, we conducted experiments utilizing a murine model of CaOx crystal deposition, induced by intraperitoneal administration of glyoxylate. An in vitro model was constructed using HK-2 cells exposed to calcium oxalate monohydrate (COM). To evaluate the effect of Dioscin on calcium oxalate crystal deposition by ROS assay, Western blotting, immunohistochemistry, Periodic Acid-Schiff staining (PAS) staining, hematoxylin-eosin (H&E) staining. Using network pharmacology and molecular docking methods, we explored the molecular mechanism of Dioscin in the treatment of CaOx-induced renal tubular epithelial cell injury. Subsequently, we conducted experiments to verify our findings.We observed a significant protective effect of Dioscin treatment against kidney oxidative stress and inflammation induced by CaOx. Then we predicted through network pharmacology that Dioscin exerts its anti-apoptotic effect through the NF-kappa B signaling pathway. Then we verified in vitro and in vivo that administration of Dioscin can alleviate the elevation of TLR4 and activation of the NF-kappa B signaling pathway induced by calcium oxalate, as well as attenuate renal apoptosis. Instead, the beneficial impact of this protection of Dioscin was reversed after overexpression of the TLR4.Dioscin has the potential to alleviate the activation of the NF-kappa B signaling pathway through TLR4, thereby exerting anti-inflammatory and anti-apoptotic effects. This study provides new ideas for the prevention and treatment of kidney stones.

Cefazolin shifts the kidney microbiota to promote a lithogenic environment

Clinical studies of the urinary tract microbiome, termed urobiome, suggest a direct, antibiotic-dependent, impact of the urobiome on kidney physiology. However, evidence for kidney bacteria comes from indirect sources or infected tissue. Further, it is unclear how antibiotics impact kidney bacteria. Here we show direct evidence for the presence of bacteria in the kidneys, with microniches in nephrons. In murine kidneys, administration of cefazolin, a commonly used perioperative antibiotic, led to a loss of uroprotective Lactobacillus spp. and proliferation of Enterobacteriaceae (which includes many known uropathogens). This effect was dependent on treatment duration, with recovery post treatment. Uroprotective L. crispatus and a strain of stone-associated E. coli differentially influenced calcium oxalate (CaOx) crystallization through the incorporation of CaOx inhibitors or promoters, respectively. In humans, microbial signatures were identified in the kidney, with unique niches between the glomeruli and tubules, established through RNA sequencing analysis and direct imaging of two independent populations. Collectively, findings support the hypothesis that the kidneys harbor a stable and antibiotic-responsive microbiota that can influence CaOx lithogenesis. The presence of unique, age-dependent microbial signatures in the glomeruli and tubuli carry implications for non-infectious kidney diseases.

Polarised light scanner for digital pathology.

Digital pathology is rapidly transforming diagnostic pathology by allowing remote work and integration of artificial intelligence solutions. Nevertheless, certain technical issues remain to be resolved. Notably, digital images captured by conventional scanners cannot be subjected to polarised light analysis [1]. We have therefore studied if images obtained using the Glissando POL Brightfield and Polarised Light Scanner are comparable to those obtained using conventional polarised light microscopy. Hematoxylin and eosin stained sections from 75 cases, including cases of amyloidosis, periprosthetic membranes, foreign body granulomas, gout, pseudogout, and breast tissues with calcium oxalate crystals were examined using both, a polarised light microscope and the Glissando POL scanner. Representative digital images were acquired for comparison. We here show that in all settings, the images obtained by conventional polarised light microscopy and using the Glissando POL scanner were comparable. We conclude that the Glissando POL scanner can be safely integrated into a digital pathology workflow.

Bis(glycinium) oxalate: effect of deuteration, single crystal neutron diffraction and Raman spectroscopic studies

AbstractThe crystal structure of bis(glycinium) oxalate (BGO) is stabilized by a very strong O–H..O hydrogen bond apart from N–H…O and C-H…O hydrogen bonds. To probe the effect of deuteration on these hydrogen bonds, fully deuterated (FDBGO), C-deuterated(CDBGO), and N-deuterated bis(glycinium) oxalate (NDBGO) crystals were grown. Single crystal neutron diffraction and Raman spectroscopic studies were carried out. It was found from neutron diffraction studies that the O…O distance of the O–H…O hydrogen bond reduced on deuteration showing an inverse Ubbelohde effect. The neutron diffraction and Raman spectroscopic studies also revealed partial deuteration. The DSC studies showed no phase transition. Variation of the melting point amongst the four crystals was in a very small range from 151 to 158 °C.

Morphoanatomy and Histochemistry of Symplocos tetrandra (Mart.) Mart. (Symplocaceae).

The Symplocaceae family comprises 406 species, all of which are classified within a single genus, Symplocos Jacq., which is distributed across multiple continents. In Brazil, this genus is predominantly found in the Atlantic Forest and Cerrado regions and is characterized by the presence of secondary metabolites, such as iridoids, terpenoids, and saponins with biological activities. Moreover, the literature research has unveiled the potential of this genus for antimicrobial, antitumor, and anti-HIV applications. This research conducted morphoanatomical, histochemical studies using light microscopy and scanning electron microscopy (SEM) analysis of the leaves and stems of Symplocos tetrandra (Mart.) Mart. Cross-sections and paradermal were performed. The investigation revealed the presence of prismatic calcium oxalate crystal in petiole and druses calcium oxalate crystals, in petiole and leaf blade. Paracytic stomata on the abaxial surface, lignified pith in the stem, which was detected with the phloroglucinol staining. Oil bodies, uniseriate epidermis, and a thin lipidic cuticle were confirmed with Sudan III. These findings suggest potential anatomical markers for taxonomic classification of the species. The data obtained in this study contributes for species identification, and the presence of metabolites can guide future pharmacological investigation with S. tetrandra.

Calcium sensing receptor regulate claudin-14 via PKA-STAT3 pathway in rat model of nephrolithiasis.

The calcium-sensitive receptor (CaSR) has been identified as a key factor in the formation of kidney stones. A substantial body of research has illuminated the function of CaSR in stone formation with respect to oxidative stress, epithelial injury, crystal adhesion, and stone-associated proteins. Nevertheless, as a pivotal molecule in renal calcium excretion, its pathway that contributes to stone formation by regulating calcium supersaturation remains underexplored. An in vitro rat calcium oxalate kidney stone model was established through the co-cultivation of calcium oxalate monohydrate (COM) with NRK-52E cells, while an in vivo model was constructed using the ethylene glycol method. Subsequently, the level of the CaSR-claudin-14 pathway was determined. To further elucidate the molecular pathway of CaSR-mediated regulation of claudin-14, drugs were selectively added to the in vitro and ex vivo kidney stone models, and the expression of claudin-14 and the levels of stone formation were detected. Moreover, the direct regulation of claudin-14 by CaSR with STAT3 serving as a transcription factor was examined via the dual luciferase assay. Eventually, a Cldn-14 knockout rat model and a model of kidney stone induction by ethylene glycol were generated using CRISPR-Cas9 technology to further clarify the role of claudin-14 in the CaSR-regulated formation of kidney stones. In vitro and in vivo observations revealed that calcium oxalate induces high expression of CaSR-claudin-14. Specifically, CaSR regulates claudin-14 expression through phosphorylation modification of STAT3 via protein kinase A (PKA). In vitro, the intervention of PKA and STAT3 reversed the elevated claudin-14 levels and stone formation induced by CaSR. Finally, we generated cldn-14 knockout rats using CRISPR-Cas9 technology and observed that ethylene glycol still induced stone formation in these animals. Nevertheless, the specific activation or inhibition of CaSR demonstrated no notable impact on stone formation. The results of our study indicate that calcium oxalate crystals induce the activation of the pro-stone pathway of CaSR. That is, activated CaSR regulates claudin-14 levels via the PKA-STAT3 pathway, which further promotes calcium salt stone formation. The role of CaSR in the regulation of stone homeostasis is further enriched.

ROS Responsive Cerium Oxide Biomimetic Nanoparticles Alleviates Calcium Oxalate Crystals Induced Kidney Injury via Suppressing Oxidative Stress and M1 Macrophage Polarization.

Emerging studies have demonstrated that M1 macrophage polarization and oxidative stress play important roles in calcium oxalate (CaOx) induced kidney injury, which leads to increased crystals deposition. ROS scavenging nanozymes and kidney-targeted nanoparticles for antioxidant drugs delivery have emerged as an arisen methodology for kidney injury therapy. However, cell membrane biomimetic-modified nanozymes as anti-inflammatory drug delivery systems for the treatment of kidney injury is rarely reported. Herein, the ROS responsive red blood cell-membrane-coated resatorvid-loaded cerium oxide nanoparticles (RBCM@CeO2/TAK-242) are constructed to suppress CaOx induced kidney injury and crystals deposition. In vitro, RBCM@CeO2/TAK-242 shows effective internalization by renal tubular epithelial cells, along with demonstrated antioxidative, anti-inflammatory, and macrophage reprogramming effects. Glyoxalate(Gly)-induced renal CaOx crystals mouse model is established, RBCM@CeO2/TAK-242 shows excellent injured kidney targeting and biosafety, and could effectively suppress CaOx induced kidney injury and crystals deposition. RBCM@CeO2/TAK-242 has a dual protective effect by both inhibiting oxidative stress and modulating macrophage polarization in vivo. In addition, RNA seq analysis reveals that RBCM@CeO2/TAK-242 protects against CaOx induced kidney injury via suppressing the TLR4/NF-κB pathway. This study provides an innovative strategy for RBCM@CeO2/TAK-242 as injured kidney targeting and dual protective effects for the treatment of CaOx induced kidney injury and crystals deposition.

Optimization of Inositol Extraction from Japanese Rice Bran and Its Potential Application in Inhibiting Calcium Oxalate Crystallization for Urolithiasis Prevention

Optimization of Inositol Extraction from Japanese Rice Bran and Its Potential Application in Inhibiting Calcium Oxalate Crystallization for Urolithiasis Prevention

Role of Rosmarinus officinalis Aqueous Extract in Relieving the Complications Associated with Ethylene Glycol-induced Urolithiasis in Male Rats

Background: Rosmarinus officinalis is considered one of the famous plants from ancient times for its therapeutic ability in many diseases, such as headache, spasms, brain disorders, and some pathological conditions associated with toxicity cases in the liver and kidneys. Aim: The current research has aimed, for the first time, to evaluate anti-urolithiatic effect of Rosmarinus officinalis aqueous extract (RMAE) on calcium oxalate stones formation in male rats and its possible therapeutic mechanisms of action. Evaluation of the polyphenols and flavonoid content in the extract was also performed. Methods: A calcium oxalate nephrolithiasis case was established in rats by adding ethylene glycol (1%) to the rats' daily drinking water for a duration of one month. Treatment was achieved by oral co-administration of RMAE to rats administrated ethylene glycol. Results: Phytochemical results showed that LC/MS-MS analysis led to the identification of 37 compounds in the phytoconstituent profile of RMAE. The biochemical results revealed significant improvement in serum kidney functions (urea, creatinine, and uric acid) in addition to restoring the calcium x phosphorous product and parathyroid hormone (PTH) levels in the plant-treated group compared to the non-treated one. The data have been supported by the significant decrease in lactate dehydrogenase enzyme (LDH) expression in the liver tissues, reflecting the decrease in oxalate synthesis in the liver compared to the non-treated group. Kidneys' histological examinations showed the absence of oxalate crystals in the treated group and the immunohistochemical findings of osteopontin (OPN) protein revealed the impact of RMAE on OPN expression in kidney tissues. Improvements in the femur bone fractures and the parathyroid gland in the treated group were also noticed during microscopic examinations. Conclusion: The anti-lithiatic effect of the extract was attributed to its influence on serum phosphate, serum PTH, and OPN levels in kidney tissues and decreasing synthesis of LDH in liver tissues in addition to the prevention of secondary disease incidences, such as secondary hyperparathyroidism and cardiovascular diseases. On the other hand, the plant's considerable content of phenolics and flavonoids has been found to play a role in controlling kidney stone progression episodes.