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The aim of this paper is to explore the mechanism of zinc-α2-glycoprotein (ZAG) forming a feedback pathway with extracellular signal- regulated kinase 1/2 (ERK1/2) and p38 to regulate epithelial mesenchymal transition (EMT) in rat renal epithelial cells (NRK-52E) induced by high uric acid environment, we divided NRK-52E into normal control group and high uric acid-induced group which was stimulated by 20 mg/dL uric acid for 48 h, and the cells in each group were transfected with overexpression of ZAG and knocked down respectively, to observe the interactions between ZAG expression level and ERK1/2 and p38 signaling pathways in the cells. The results revealed that the mRNA and protein expression of EMT-related molecules were elevated in rat kidney cells under high uric acid environment compared with the normal culture group (P<0.05); up-regulation of ZAG decreased the expression of mitogen-activated protein kinase kinase (MAPKK), ERK1/2, p38, activated transcription factor-2 (ATF2) and protein kinase B (PKB or Akt) mRNA in this pathway in rat kidney epithelial cells under high uric acid environment culture (P<0.01), while the downregulation of ZAG increased (P<0.05). At the protein level, the expression of MAPKK, p38 and Akt decreased in the ZAG up-regulated group compared to the untransfected group (P<0.05, P<0.01, P<0.001); and the expression of ERK1/2, p38 and Akt was elevated in the ZAG down-regulated group (P<0.001, P<0.05, P<0.01). The results suggest that transfection up-regulation of ZAG decreases the expression of laminin and vimentin mRNA, the marker genes related to EMT in NRK-52E; regulation of ZAG expression in NRK-52E can play a positive role in ERK1/2 and p38 signaling pathways, and thus inhibit renal cell EMT. This study provides an experimental basis for clinical treatment of hyperuricemic nephropathy (HN). [ABSTRACT FROM AUTHOR]

Hyperuricemia (HUA) is a prevalent chronic disease, characterized by excessive blood uric acid levels, that poses a significant health risk. In this study, the preventive effects and potential mechanisms of ethanol extracts from Chinese sumac (Rhus chinensis Mill.) fruits on HUA and uric acid nephropathy were comprehensively investigated. The results demonstrated a significant reduction in uric acid levels in hyperuricemia mice after treatment with Chinese sumac fruit extract, especially in the high-dose group, where the blood uric acid level decreased by 39.56%. Visual diagrams of the kidneys and hematoxylin and eosin (H&E)-stained sections showed the extract's effectiveness in protecting against kidney damage caused by excessive uric acid. Further investigation into its mechanism revealed that the extract prevents and treats hyperuricemia by decreasing uric acid production, enhancing uric acid excretion, and mitigating the oxidative stress and inflammatory reactions induced by excessive uric acid in the kidneys. Specifically, the extract markedly decreased xanthine oxidase (XOD) levels and expression in the liver, elevated the expression of uric acid transporters ABCG2, and lowered the expression of uric acid reabsorption proteins URAT1 and SLC2A9. Simultaneously, it significantly elevated the levels of endogenous antioxidant enzymes (SOD and GSH) while reducing the level of malondialdehyde (MDA). Furthermore, the expression of uric-acid-related proteins NLRP3, ACS, and Caspase-3 and the levels of IL-1β and IL-6 were significantly reduced. The experimental results confirm that Chinese sumac fruit extract can improve HUA and uric acid nephropathy in mice fed a high-purine yeast diet. This finding establishes a theoretical foundation for developing Chinese sumac fruit as a functional food or medicine for preventing and treating HUA. [ABSTRACT FROM AUTHOR]

Uric acid nephropathy (UAN) is caused by purine metabolism disorders. UAN rat models were established in SD rats. The modeling rats received different doses of hispidulin (10, 20, 50 mg/mL). Febuxostat was applied as the positive drug. Serum creatinine, uric acid (UA), and cystatin‐C (cys‐C), neutrophil gelatinase‐associated lipocalin (NGAL), IL‐1β, IL‐8, TNF‐α, and IL‐6 in rats were detected. HE staining was done to assess kidney injury. UAN rats possessed prominent levels of serum creatinine, UA, cys‐C, and NGAL, which all reduced after hispidulin treatment in a dose‐dependent manner. HE staining determined the improvement of kidney injury after treatment, which was comparable to the efficacy of febuxostat. Hispidulin inhibited the release of IL‐1β, IL‐8, TNF‐α, and IL‐6 in UAN rats. Hispidulin enhanced autophagy in UAN rats, presenting as ascending LC3II/I ratio and downregulated P62. The increasing trend of inflammasome‐related proteins of NLRP3 and Caspase‐1 was changeovered by hispidulin. The activation of NF‐kB signaling was intercepted by hispidulin in UAN rats. Hispidulin can effectively improve renal function injury caused by UAN in rats. The mechanism may be related to the inhibition of inflammatory response induced by autophagy and activation of NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Hyperuricemia (HUA) is a prevalent chronic disease, characterized by excessive blood uric acid levels, that poses a significant health risk. In this study, the preventive effects and potential mechanisms of ethanol extracts from Chinese sumac (Rhus chinensis Mill.) fruits on HUA and uric acid nephropathy were comprehensively investigated. The results demonstrated a significant reduction in uric acid levels in hyperuricemia mice after treatment with Chinese sumac fruit extract, especially in the high-dose group, where the blood uric acid level decreased by 39.56%. Visual diagrams of the kidneys and hematoxylin and eosin (H&E)-stained sections showed the extract’s effectiveness in protecting against kidney damage caused by excessive uric acid. Further investigation into its mechanism revealed that the extract prevents and treats hyperuricemia by decreasing uric acid production, enhancing uric acid excretion, and mitigating the oxidative stress and inflammatory reactions induced by excessive uric acid in the kidneys. Specifically, the extract markedly decreased xanthine oxidase (XOD) levels and expression in the liver, elevated the expression of uric acid transporters ABCG2, and lowered the expression of uric acid reabsorption proteins URAT1 and SLC2A9. Simultaneously, it significantly elevated the levels of endogenous antioxidant enzymes (SOD and GSH) while reducing the level of malondialdehyde (MDA). Furthermore, the expression of uric-acid-related proteins NLRP3, ACS, and Caspase-3 and the levels of IL-1β and IL-6 were significantly reduced. The experimental results confirm that Chinese sumac fruit extract can improve HUA and uric acid nephropathy in mice fed a high-purine yeast diet. This finding establishes a theoretical foundation for developing Chinese sumac fruit as a functional food or medicine for preventing and treating HUA.

[Display omitted] • BBR was bound to RBCs in the UAN mice, which can be recognized and phagocytosed by macrophages. • BBR was recruited to the injured kidney and functioned, in the UAN mice, after binding to RBCs. • BBR activated AMPK, inhibited the activation of inflammatory pathway NF-κB and regulated macrophage polarization to ameliorate kidney injury. • The anti-inflammatory and macrophage polarization regulation effects of BBR were completely reversed upon administration of Compound C, an AMPK inhibitor. Uric acid nephropathy (UAN), caused by a common metabolic disorder resulting from hyperuricemia (HUA), has an increasing incidence. Previous studies have shown that berberine (BBR) has clear urate-lowering and anti-inflammatory effects in UAN mice, but its mechanism needs to be further clarified. Therefore, Potassium Oxonate (PO) combined with hypoxanthine (HX) induced UAN mice model and MSU induced THP-1 cells polarization model were adopted to investigate the mechanism of BBR on UAN in terms of tissue distribution and molecular pharmacology. Study unveiled that BBR was first found to bind to red blood cells (RBCs), which were recognized and phagocytosed by monocytes, then recruited by the injured kidney. Subsequently, BBR was enriched and functional in damaged kidney. The results of in vivo experiments revealed that, BBR reduced UA, BUN, CRE levels as well as the release of TNF-α, IL-1β, IL-18 and IL-6, and alleviated renal injury in UAN mice, as consistent with previous studies. Additionally, BBR decreased MCP-1 expression, while diminishing macrophage infiltration and decreasing M1 proportion as determined by RT-qPCR. In vitro experiments, demonstrated that MSU promoted inflammatory polarization of THP-1 cells, while BBR reduced synthesis of inflammatory factors and inhibited MSU-induced inflammatory polarization. These effects of BBR were dependent on AMPK activation along with indirect inhibition of NF-κB signaling pathway mediated. However, the anti-inflammatory and macrophage polarization regulation effects of BBR were completely reversed upon administration of Compound C, an AMPK inhibitor. Therefore, BBR ameliorated kidney injury via regulating macrophage polarization through AMPK, which has therapeutic potential for UAN patients. [ABSTRACT FROM AUTHOR]

Background: Uric acid nephropathy (UN) is a complication of hyperuricemia (HUA), which has a great impact on people's lives. Here, we evaluated the therapeutic potential of total flavonoids of Phellinus igniarius (TFPI) in vivo and studied the anti UN effect of TFPI in vitro. Methods: Hyperuricemia was induced by intraperitoneal injection of potassium oxonate in ICR mice. After intervention with TFPI, we evaluated the levels of serum uric acid (UA) and creatinine (CR), and the contents of xanthine oxidase (XOD) and adenosine deaminase (ADA) in liver. To explore the effect and molecular mechanism of TFPI on UN, we treated HK-2 cells with monosodium urate (MSU) to study the effect of TFPI on apoptosis and inflammation. In addition, to explore the mechanism of TFPI on uric acid transport we evaluated the relationship between uric acid transporter ABCG2 and inflammatory signaling pathway TLR4-NLRP3. Results: In the model mice, TFPI significantly decreased the levels of UA and Cr, which may be related to the inhibition of XOD enzyme activity. In HK-2 cells, the response of TFPI to MSU can effectively inhibit apoptosis and activation of TLR4-NLRP3 signaling pathway and promote the expression of ABCG2. Conclusions: TFPI can significantly inhibit the release of inflammatory factors and promote the expression of ABCG2 by targeting TLR4 receptor and NLRP3 inflammasome. And targeted inhibition of XOD enzyme activity to reduce uric acid level and inhibit the development of UN.

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 μmol/L vs. 325.60 ± 18.65 μmol/L, p

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 μmol/L vs. 325.60 ± 18.65 μmol/L, p < 0.001), serum creatinine (66.20 ± 11.88 μmol/L vs. 182.20 ± 8.87 μmol/L, p < 0.001) and BUN level (13.33 ± 3.16 mmol/L vs. 36.04 ± 6.60 mmol/L, p < 0.001). The treatment group also displayed attenuated renal pathological lesions and metabolic endotoxemia (25.60 ± 5.90 ng/mL vs. 38.40 ± 4.98 ng/mL, p < 0.01), and improved tightly linked proteins expression. Besides, curcumin altered the gut microbiota structure in UAN rats. More specifically, curcumin treatment protected against the overgrowth of opportunistic pathogens in UAN, including Escherichia-Shigella and Bacteroides, and increased the relative abundance of bacteria producing short‐chain fatty acids (SCFAs), such as Lactobacillus and Ruminococcaceae. These results suggest that curcumin could modulate gut microbiota, fortify the intestinal barrier, attenuate metabolic endotoxemia, and consequently protect the renal function in UAN rats. [ABSTRACT FROM AUTHOR]

The abnormal production and/or excretion of uric acid can lead to a disorder in uric acid metabolism, resulting in hyperuricemia, uric acid nephropathy, gouty arthritis, and other diseases related to uric acid metabolism disorder. The clinical incidence of these diseases is increasing year after year, posing a significant threat to public health. In the past, hyperuricemia and gouty arthritis were often considered different diseases, with uric acid nephropathy being a complication of hyperuricemia. However, recent research has challenged this perspective, suggesting that hyperuricemia, uric acid nephropathy, and gouty arthritis are different stages of the same disease, with urate deposition as the common pathological feature. This article offered a comprehensive overview of the current understanding of hyperuricemia, uric acid nephropathy, and gouty arthritis in both traditional Chinese medicine(TCM) and western medicine. It delved into the most up-to-date insights into the involvement of urate deposition in the pathogenesis of uric acid metabolism disorders and highlighted the dominant role of TCM in the prevention and treatment of uric acid metabolism disorders, so as to provide a reference for effective intervention strategies and drug development in uric acid metabolism disorder-related diseases.

Uric acid metabolic disorder is considered to be the main pathogenesis of uric acid nephropathy (UN). Smilax glabra Roxb. is a traditional Chinese herb which has been used in the treatment of gout, but the mechanism was unclear. In this study, we investigated the protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. (SGF) on uric acid nephropathy rats and its underlying mechanisms of promoting uric acid excretion. Sprague Dawley (SD) rats were induced by high purine diet (yeast pellets + adenine) for 5 weeks. Rats were orally treated with SGF or allopurinol daily. The biochemical parameters and enzymes in different treated rats were determined by commercial kits. Kidney pathology was visualized using optical microscopy and electron microscopy. Renal inflammatory factors were detected by ELISA. Renal fibrosis factors and uric acid transporters were analyzed by real time RT-PCR and western blot. The results showed that SGF significantly improved kidney function. Histopathologic examination revealed that urate-induced renal damage was markedly reversed by SGF. Meanwhile, SGF treatment was also found to significantly inhibit renal oxidative stress. SGF treatment obviously suppressed the inflammatory factors of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and the profibrotic factors of basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1) expression in UN rats. Moreover, SGF either significantly inhibited uric acid production or promoted uric acid excretion in UN rats. The mechanism of SGF promoting uric acid excretion was related to its increase of ATP-binding cassette transporter G2 (ABCG2), organic anion transporter 1 (OAT1), organic anion transporters 2 (OCT2) and organic cation/carnitine transporters 2 (OCTN2) expression. In conclusion, SGF could ameliorate renal oxidative stress and inflammation in UN rats through promoting uric acid excretion.

Objective: By copying the uric acid nephropathy rat model, the oxidative stress injury of mitochondria was caused in renal tubular epithelial cells and the relationship between the injury and the induction of cell apoptosis was identified. Methods: All rats were randomly divided into NC (normal control, NC) group, HUA (high uric acid, HUA) group and GSH (reductive glutathione, GSH) group. The values were quantitatively tested in the kidney tissues, including 24-h urinary protein quantity, serum creatinine, blood uric acid, the MDA (malondialdehyde, MDA) and SOD (superoxide dismutase, SOD) oxidative stress indicators. The expression of p53, Bax and caspase-9/-3 were detected by immunoblotting. TUNEL assays were used to detect the apoptosis of renal tubular epithelial cells. Result: In HUA and GSH groups, the 24-h urinary protein(24UTP), serum creatinine, and blood uric acid increased gradually with the increase of the replication cycle and the increase was significant compared to the NC group (p

Uric acid nephropathy (UAN) is caused by excessive uric acid, which results in the damage of renal tissue via urate crystals deposition in the kidneys. The roots and rhizomes of Salvia miltiorrhiza Bunge (S. miltiorrhiza) have been clinically used in many prescriptions to treat uric acid-induced renal damage. This study investigates the uricosuric and nephroprotective effects of the ethyl acetate extract of S. miltiorrhiza (EASM) and tanshinone IIA (a major component of S. miltiorrhiza, Tan-IIA) on UAN and explores the underlying molecular mechanism. Both EASM and Tan-IIA significantly decreased serum uric acid (SUA), serum creatinine (SCR), urine uric acid (UUA), and increased urine creatinine (UCR), and blood urea nitrogen (BUN) levels in experimental UAN mice. In adenine and potassium oxonate-induced mice, EASM and Tan-IIA treatment alleviated renal dysfunction and downregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Moreover, EASM treatment significantly prevented excessive reactive oxygen species (ROS) production in uric acid-induced HK-2 cells and suppressed the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). EASM also suppressed ROS-activated mitogen-activated protein kinases (MAPKs) in vivo and in vitro. These results suggest that both EASM and Tan-IIA demonstrated inhibitory effects on UAN through relieving NOX4-mediated oxidative stress and suppressing MAPK pathways activation. [ABSTRACT FROM AUTHOR]

Objective: By copying the uric acid nephropathy rat model, the oxidative stress injury of mitochondria was caused in renal tubular epithelial cells and the relationship between the injury and the induction of cell apoptosis was identified. Methods: All rats were randomly divided into NC (normal control, NC) group, HUA (high uric acid, HUA) group and GSH (reductive glutathione, GSH) group. The values were quantitatively tested in the kidney tissues, including 24-h urinary protein quantity, serum creatinine, blood uric acid, the MDA (malondialdehyde, MDA) and SOD (superoxide dismutase, SOD) oxidative stress indicators. The expression of p53, Bax and caspase-9/-3 were detected by immunoblotting. TUNEL assays were used to detect the apoptosis of renal tubular epithelial cells. Result: In HUA and GSH groups, the 24-h urinary protein(24UTP), serum creatinine, and blood uric acid increased gradually with the increase of the replication cycle and the increase was significant compared to the NC group (p <.05). Compared to the NC group, MDA increased whereas SOD decreased. The expression of apoptotic proteins, such as p53, Bax, and caspase-9/-3 in the mitochondria was significantly different (p <.05). TUNEL assay revealed that the renal tubular epithelial cells in HUA group were largely apoptotic, whereas the GSH group improved significantly. Conclusion: Mitochondria incurred the substantial damage due to being in a state of oxidative stress, which was the primary cause of apoptosis in the renal tubule epithelial cells. GSH exhibited the effective resistance to the influence of oxidative stress and can restore the damage in the renal tubular epithelial cells. [ABSTRACT FROM AUTHOR]

Abstract Uric acid metabolic disorder is considered to be the main pathogenesis of uric acid nephropathy (UN). Smilax glabra Roxb. is a traditional Chinese herb which has been used in the treatment of gout, but the mechanism was unclear. In this study, we investigated the protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. (SGF) on uric acid nephropathy rats and its underlying mechanisms of promoting uric acid excretion. Sprague Dawley (SD) rats were induced by high purine diet (yeast pellets + adenine) for 5 weeks. Rats were orally treated with SGF or allopurinol daily. The biochemical parameters and enzymes in different treated rats were determined by commercial kits. Kidney pathology was visualized using optical microscopy and electron microscopy. Renal inflammatory factors were detected by ELISA. Renal fibrosis factors and uric acid transporters were analyzed by real time RT-PCR and western blot. The results showed that SGF significantly improved kidney function. Histopathologic examination revealed that urate-induced renal damage was markedly reversed by SGF. Meanwhile, SGF treatment was also found to significantly inhibit renal oxidative stress. SGF treatment obviously suppressed the inflammatory factors of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and the profibrotic factors of basic fibroblast growth factor (bFGF), transforming growth factor-β 1 (TGF-β 1) expression in UN rats. Moreover, SGF either significantly inhibited uric acid production or promoted uric acid excretion in UN rats. The mechanism of SGF promoting uric acid excretion was related to its increase of ATP-binding cassette transporter G2 (ABCG2), organic anion transporter 1 (OAT1), organic anion transporters 2 (OCT2) and organic cation/carnitine transporters 2 (OCTN2) expression. In conclusion, SGF could ameliorate renal oxidative stress and inflammation in UN rats through promoting uric acid excretion. [ABSTRACT FROM AUTHOR]

Abstract This study is designed to explore the mechanism by which long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) plays a pathogenic role in uric acid nephropathy (UAN). The expressions of ANRIL, miR-122-5p, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and NOD-like receptor protein 3 (NLRP3) were determined in UAN patients and uric acid-treated HK-2 cells by qRT-PCR. Protein levels of BRCC3 and NLRP3 were examined by western blot. The levels of inflammatory cytokines were quantified by ELISA. CCK-8 assay was used to assess cell viability. Apoptosis was detected by Annexin V-FITC/PI double-labeled flow cytometry and TUNEL assay. The interaction between ANRIL, miR-122-5p and BRCC3 were studied using luciferase reporter assay. The role of ANRIL in renal injury was evaluated in experimental rats. ANRIL and BRCC3 were highly expressed while miR-122-5p was down-regulated in serum of UAN patients and uric acid-treated tubular epithelial cells. Luciferase reporter assay and in vitro rescue experiment confirmed that ANRIL promoted NLRP3 inflammasome activation by up-regulating BRCC3 expression via sponging miR-122-5p. Furthermore, in vivo experiment validated that knockdown of ANRIL alleviated renal injury of UAN rats. ANRIL exerted pathogenic effect in UAN to promote NLRP3 inflammasome activation via miR-122-5p/BRCC3 axis. Highlights • ANRIL was highly expressed in UAN patients and uric acid-treated tubular epithelial cells. • ANRIL promoted NLRP3 inflammasome activation by increasing BRCC3 expression via sponging miR-122-5p. • Knockdown of ANRIL alleviated renal injury of UAN rats. [ABSTRACT FROM AUTHOR]

Abstract The prevalence of gout is relatively high worldwide, and many gout patients suffer from uric acid nephropathy (UAN) concomitantly. ELR-CXC chemokines such as CXCL8 and CXCL1 have a elevated expression in UAN. In this research, a mouse UAN model was established for a 12 week duration, and uric acid-related crystals were observed. CXCL8(3–72)K11R/G31P (G31P) is a mutant protein of CXCL8/interleukin 8 (IL-8), which has been reported to have therapeutic efficacy in both inflammatory diseases and malignancies for it acts as a selective antagonist towards CXCR1/CXCR2. In this study, G31P-treated mice showed declined production of the blood urea nitrogen (BUN) level and urine volume in UAN mice compared with G31P-untreated UAN counterparts. In addition, G31P effectively improved renal fibrosis, and reduced uric acid accumulation and leukocyte infiltration in UAN kidneys. Furthermore, the expressions of CXCL1 and CXCL2 were reduced and the activation of NOD-like receptors protein 3 (NLRP3) was inhibited by G31P treatment. This study has demonstrated that G31P attenuates inflammatory progression in chronic UAN, and plays a renoprotective function. [ABSTRACT FROM AUTHOR]

Uric acid nephropathy (UAN) is caused by excessive uric acid, and is a key risk factor for uric acid nephrolithiasis, gouty arthritis, renal diseases and cardiovascular diseases. The present study aimed to evaluate the protective effect of fucoidan, a sulfated polysaccharide component of brown algae, on UAN and to elucidate the underlying molecular mechanism. A rat model of UAN was induced by adenine treatment, and rats were then randomly assigned to control, model or fucoidan treatment groups. Hematoxylin and eosin staining of the kidney tissues of rats with UAN was subjected to conventional morphological evaluation. Cellular infiltrate in the tubules, atrophic glomeruli, tubular ectasia, granuloma hyperplasia focal fibrosis and accumulated urate crystals in the tubules of UAN rat renal tissues were observed. These symptoms of kidney damage were reduced in the fucoidan treatment group. Periodic acid methenamine silver. Masson staining was performed and the results indicated that renal interstitial fibrosis was reduced among renal tissues from the fucoidan treatment group compared with the model group. Terminal deoxynucleotidyl.transferase.mediated dUTP nick end labelling staining revealed a lower proportion of apoptotic nuclei in the kidneys of the fucoidan treatment group compared with the model group. Protein kinase A (PKA) 2β and phosphorylated PKA 2β protein levels were significantly elevated in renal tissues of the fucoidan treatment group compared with the model group (P<0.05 and P<0.01, respectively), suggesting that PKA expression was upregulated by fucoidan. Immunohistochemistry staining of PKA in rat renal tissues demonstrated increased expression of PKA. The surface organic cation transporter 2 (OCT2) level was significantly increased by fucoidan treatment compared with the model group (P<0.01), with no significant change in total OCT2 level. COS.7 cells ectopically expressing OCT2 were established. It was indicated that fucoidan was able to activate PKA and upregulate surface OCT2 in OCT2.expressing COS.7 cells. This further demonstrated that upregulation of surface OCT2 expression in OCT2.expressing cells was induced by PKA upregulation. In conclusion, fucoidan upregulated surface OCT2 expression in renal tissues to alleviate the symptoms of UAN via upregulated expression of PKA. [ABSTRACT FROM AUTHOR]

• QL activates autophagy by regulating AMPK/Stat3 pathway in UAN. • AMPK/Stat3 pathway is implicated in UA-induced NLRP3 inflammasome activation. • QL attenuates renal immune inflammatory damage in UAN rats via modulating AMPK/Stat3 mediated autophagy. Excessive deposition of uric acid (UA) is one of the risk factors for kidney damage. Qinling liquid (QL) has a certain therapeutic effect on uric acid nephropathy (UAN), but its regulation mechanism is still unclear. UAN rat models and UA induced rat renal tubular epithelial cells (NRK-52E) were constructed to evaluate the functional roles of QL. We firstly evaluated the kidney function and the degree of kidney damage in rats after QL treatment. Then, effects of QL on autophagy and NLRP3 inflammasome activation were assessed. Moreover, the regulation of QL in AMPK and Stat3 phosphorylation levels and the relationship among autophagy, AMPK/Stat3 pathway and NLRP3 inflammasomes were determined. QL could alleviate the inflammatory damage in UAN rats and promote the activation of autophagy. In addition, QL suppressed UA-induced activation of NLRP3 inflammasomes in rat renal tubular epithelial cells, which was partially reversed by autophagy inhibitor. Further, AMPK/Stat3 axis-mediated autophagy participated in the regulation of UA-induced NLRP3 inflammasome activation in NRK-52E cells. Finally, we confirmed that inhibiting AMPK/Stat3 pathway partly deteriorated the ameliorating effect of QL on renal immune inflammatory injury in UAN rats. Through in vivo and in vitro experiments, we found that QL promotes autophagy by activating the AMPK/Stat3 pathway, thereby improving renal immune inflammatory injury in UAN. [ABSTRACT FROM AUTHOR]

Background: Uric acid nephropathy (UN) is a complication of hyperuricemia (HUA), which has a great impact on people's lives. Here, we evaluated the therapeutic potential of total flavonoids of Phellinus igniarius (TFPI) in vivo and studied the anti UN effect of TFPI in vitro., Methods: Hyperuricemia was induced by intraperitoneal injection of potassium oxonate in ICR mice. After intervention with TFPI, we evaluated the levels of serum uric acid (UA) and creatinine (CR), and the contents of xanthine oxidase (XOD) and adenosine deaminase (ADA) in liver. To explore the effect and molecular mechanism of TFPI on UN, we treated HK-2 cells with monosodium urate (MSU) to study the effect of TFPI on apoptosis and inflammation. In addition, to explore the mechanism of TFPI on uric acid transport we evaluated the relationship between uric acid transporter ABCG2 and inflammatory signaling pathway TLR4-NLRP3., Results: In the model mice, TFPI significantly decreased the levels of UA and Cr, which may be related to the inhibition of XOD enzyme activity. In HK-2 cells, the response of TFPI to MSU can effectively inhibit apoptosis and activation of TLR4-NLRP3 signaling pathway and promote the expression of ABCG2., Conclusions: TFPI can significantly inhibit the release of inflammatory factors and promote the expression of ABCG2 by targeting TLR4 receptor and NLRP3 inflammasome. And targeted inhibition of XOD enzyme activity to reduce uric acid level and inhibit the development of UN., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: To study the expression and effect of interleukin1 (IL-1) β and interleukin-1 receptor-associated kinase 4 (IRNK-4) in Uric Acid Nephropathy Rats, and investigate the significance of IL-1β Signaling Pathway in the development of uric acid nephropathy. Methods: 54 Wistar rats were randomly divided into hyperuricemia group and normal control group. Establishing the rats model group to examine the levels of uric acid (UA) , serum urea nitrogen (BUN), serum creatinin (CR) and 24 h urinary microalbumin (mA1b) in each group; Morphological changes were observed by HE staining; The expression levels of L-1β in renal tissue were detected by immunohistochemical method; The expression levels of IRAK-4 were detected by fluorescent quantitation PCR. Results: The Expression level of IL-1β was significantly higher in the hyperuricemia group after 2, 4, 6 weeks (P<0.01); IRAK-4 mRNA in renal tissue were increased in hyperuricemia group after 2,4,6 weeks, and significantly higher in 4-6 weeks (P<0.01). Conclusion: The expression of IL-1β and IRAK-4 may be associated with the progress of inflammation in uric acid nephropathy, which will provide a new option for treatment of this disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] IGPS is isolated from traditional Chinese herb P. scandens (LOUR.) MERRILL. [•] Protective effects of IGPS on UAN rats induced by yeast and PO were assessed. [•] IGPS could alleviate high uric acid-induced nephropathy injury. [•] IGPS could decrease SBP by up regulation NOS-1 expression. [•] IGPS shows immunomodulatory properties by inhibiting TNF-α and TGF-β1 expression. [Copyright &y& Elsevier]

A 25-year-old man presented with acute kidney injury (AKI), massive proteinuria and hyperuricemia after epileptic seizures. His AKI improved along with the disappearance of proteinuria after corticosteroid treatment. A kidney biopsy revealed no significant glomerular abnormalities, but varying degrees of tubular injury, such as proximal tubular simplification, mild distal tubular proliferation, and Tamm-Horsfall protein-like material accumulation with extravasation into the interstitium, were noted. A further analysis revealed the intratubular depositions of uric acid crystals, indicating the involvement of acute uric acid nephropathy associated with seizures. Our patient's condition is rare, and the clinicopathological aspects of the diagnostic challenges are discussed.

Abstract: Aims: Uric acid nephropathy (UAN) is due to excessive uric acid, which leads to hyperuricemia and kidney damage via the deposition of urate microcrystals in the kidneys. Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from the traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). This study aimed to evaluate the anti-inflammatory and immunomodulatory effects of IGPS and its mechanism on UAN rats. Main methods: The experimental model of UAN rats was induced by using uricopoiesis promoter adenine and uricase inhibitor potassium oxonate (PO). Treatment groups received three different doses of IGPS, allopurinol (AP) and benzbromarone (BEN) daily for 24days respectively. The histopathology of renal tissues in UAN rats were assessed for conventional morphological evaluation. The nuclear factor-κBp65 (NF-κBp65), monocyte chemoattractant protein-1 (MCP-1) and α-smooth muscle actin (α-SMA) protein expression of renal tissues in UAN rats were investigated by immunohistochemistry. MCP-1 and α-SMA mRNA levels were monitored by method of reverse transcription polymerase chain reaction (RT-PCR). Key findings: Treatment with IGPS significantly ameliorated UAN induced renal tissue injury, inhibited the biological activity of NF-κBp65, MCP-1 and α-SMA, and suppressed the mRNA expressions of MCP-1 and α-SMA. Significance: IGPS exerts a protective effect against renal injury in UAN rats, possesses anti-inflammatory and immunomodulatory effects by inactivating NF-κBp65 pathway transmembrane signal transduction, down regulating the expression of MCP-1 and α-SMA to modulate pro-inflammatory mediator production in nephropathy tissue to improve renal fibrosis in UAN rats. [Copyright &y& Elsevier]

Acute renal failure developed during the first 3 days after birth in a newborn subsequently diagnosed with hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) deficiency. Fluid infusion and allopurinol therapy normalised renal function and serum uric acid levels. Only a few cases of acute renal failure due to acute hyperuricemic nephropathy related to HPRT deficiency have previously been reported in infants, and there are no reported cases in newborns as young as 3 days old. [ABSTRACT FROM AUTHOR]

We report a case of Castleman’s disease that developed tumor lysis syndrome spontaneously and after systemic chemotherapy. A 44-year-old male patient was admitted with a 2-week history of abdominal distension accompanied by dyspnea. Physical examination revealed multiple lymph node enlargements. After admission, spontaneous hemoperitoneum developed and he underwent exploratory laparotomy, with the removal of the ruptured spleen. Pathologic review of the splenic tissue and excised lymph node gave the diagnosis of multicentric Castleman’s disease. He experienced two episodes of tumor lysis syndrome, initially spontaneous and then chemotherapy related, which needed vigorous management including hemodialysis and intensive fluid therapies. To our knowledge, this is the first reported case of Castleman’s disease complicated by tumor lysis syndrome. This suggests that the possibility of tumor lysis syndrome should be considered when treating Castleman’s disease with a large disease burden. [ABSTRACT FROM AUTHOR]

This report is about a 23-year-old man who required hemodialysis in connection with an acute renal failure resulting from uric acid nephropathy without hyperuricemia. After recovering renal function he showed extreme hypouricemia (0,1-0,3 mg/dl) and elevated uric acid clearance (100-300 ml/min). The fractional excretion of uric acid (Cua/Cer) could be suppressed by oral pyrazinamide and enhanced by probenecid. As no other renal tubular or metabolic abnormalities were detected, it is suggested that a markedly increased renal tubular urate secretion was responsible for the hypouricemia and also for the rare side-effect of an uric acid nephropathy in this patient. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved., Materials and Methods: HK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t -test was used to analyze the difference between groups., Results: Myosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses., Conclusion: The Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy.

• Rhein inhibits apoptosis and inflammatory injury of UAN. • LincRNA-Cox2 regulates STAT1 expression by sponging miR-150-5p. • Rhein attenuates inflammatory injury of UAN via lincRNA-Cox2/miR-150-5p/STAT1 axis. Rhein has protective effect on uric acid nephropathy (UAN). This article aims to demystify the mechanism of function of rhein in UAN. Mouse kidney epithelial cell line (TCMK-1) was incubated with uric acid (UA) to induce inflammatory injury. Then, the TCMK-1 cells were treated with rhein. The relationships among lincRNA-Cox2, miR-150-5p and STAT1 were evaluated by luciferase reporter assay. CCK8 and flow cytometry were performed to detect cell proliferation and apoptosis. The levels of IL-6, IL-1β and TNF-α were investigated by enzyme linked immunosorbent assay. Western blot and quantitative real-time PCR were performed to examine the expression of genes and proteins. We found that UA suppressed proliferation and enhanced apoptosis and the levels of IL-6, IL-1β and TNF-α of TCMK-1 cells, which was effectively improved by rhein treatment. Furthermore, lincRNA-Cox2 overexpression caused an increase of apoptosis and inflammatory factors in the rhein-treated TCMK-1 cells. LincRNA-Cox2 regulated STAT1 expression by sponging miR-150-5p. And lincRNA-Cox2 promoted apoptosis and inflammatory injury of TCMK-1 cells by regulating miR-150-5p/STAT1 axis. In summary, our studies demonstrate that rhein has a protective effect against UAN by inhibiting renal inflammatory injury via lincRNA-Cox2/miR-150-5p/STAT1 axis. [ABSTRACT FROM AUTHOR]

Spontaneous tumor lysis syndrome (SPTLS) is a rare phenomenon that can manifest in rapidly proliferating hematological malignancies and solid tumors prior to initiating cytotoxic therapy. We encountered a patient who originally presented with diffuse lymphadenopathy, abdominal distention, and dyspnea, who had laboratory abnormalities suggestive of SPTLS. His peripheral flow cytometry and lymph node biopsy revealed blastoid-variant mantle cell lymphoma. Prior to initiating chemotherapy, acute kidney injury (AKI) and uric acid had improved with intravenous fluids and the initiation of allopurinol. However, after beginning chemotherapy, the patient developed a second AKI concerning for tumor lysis syndrome (TLS). He went on to have renal recovery and did not require renal replacement therapy. With the exception of case reports, there is limited evidence to guide general medicine clinicians who encounter cases of SPTLS. Expert-based guidelines are available to guide use of rasburicase, an uricase enzyme, before initiation of chemotherapy for certain malignancies when risk for TLS is considered high. Despite these guidelines, the role of rasburicase in preventing AKI remains controversial after inconclusive results in a meta-analysis. The causative relationship between uric acid and AKI in TLS is based on a mechanism of tubular obstruction. There are also mechanisms by which uric acid may cause AKI without tubular obstruction related to acute hyperuricemic nephropathy. Further characterization of the role of uric acid in causing AKI in patients without tubular obstruction may identify new mechanisms of injury and offer insight into new treatment strategies.

Uric acid nephropathy (UAN) is caused by excessive uric acid, and is a key risk factor for uric acid nephrolithiasis, gouty arthritis, renal diseases and cardiovascular diseases. The present study aimed to evaluate the protective effect of fucoidan, a sulfated polysaccharide component of brown algae, on UAN and to elucidate the underlying molecular mechanism. A rat model of UAN was induced by adenine treatment, and rats were then randomly assigned to control, model or fucoidan treatment groups. Hematoxylin and eosin staining of the kidney tissues of rats with UAN was subjected to conventional morphological evaluation. Cellular infiltrate in the tubules, atrophic glomeruli, tubular ectasia, granuloma hyperplasia focal fibrosis and accumulated urate crystals in the tubules of UAN rat renal tissues were observed. These symptoms of kidney damage were reduced in the fucoidan treatment group. Periodic acid methenamine silver-Masson staining was performed and the results indicated that renal interstitial fibrosis was reduced among renal tissues from the fucoidan treatment group compared with the model group. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling staining revealed a lower proportion of apoptotic nuclei in the kidneys of the fucoidan treatment group compared with the model group. Protein kinase A (PKA) 2β and phosphorylated PKA 2β protein levels were significantly elevated in renal tissues of the fucoidan treatment group compared with the model group (P<0.05 and P<0.01, respectively), suggesting that PKA expression was upregulated by fucoidan. Immunohistochemistry staining of PKA in rat renal tissues demonstrated increased expression of PKA. The surface organic cation transporter 2 (OCT2) level was significantly increased by fucoidan treatment compared with the model group (P<0.01), with no significant change in total OCT2 level. COS-7 cells ectopically expressing OCT2 were established. It was indicated that fucoidan was able to activate PKA and upregulate surface OCT2 in OCT2-expressing COS-7 cells. This further demonstrated that upregulation of surface OCT2 expression in OCT2-expressing cells was induced by PKA upregulation. In conclusion, fucoidan upregulated surface OCT2 expression in renal tissues to alleviate the symptoms of UAN via upregulated expression of PKA.