Nephropathy In Rats Research Articles

Effects of Valsartan on LN, FN, MDA, Renal Tissue Fibrosis, and Inflammatory Infiltration in DN Rats.

The effects of valsartan on laminin (LN), fibronectin (FN), malondialdehyde (MDA), renal tissue fibrosis, and inflammatory infiltration in diabetic nephropathy (DN) rats are explored. A total of 42 SPF male Sprague D (SD) rats are selected and randomly divided into normal set, model set, valsartan low-dose and high-dose sets, and metformin set with 7 rats in each set. The kidney tissue of all rats is collected after administration. The standard of protein mRNA in kidney tissues is detected by real-time fluorescence quantitative polymerase chain reaction (PCR) method, and the protein standard in kidney tissues is detected by western blot. The experimental results show that the application of valsartan to DN rats can effectively relieve the morphology of the rat kidney tissue, enhance the protein expression in the kidney tissue of the DN rats, and reduce the fibrosis and inflammatory infiltration of the kidney tissue.

Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade

BackgroundPodocytes have become a crucial target for interventions in proteinuric kidney diseases. Many studies have reported that overexpression of transient receptor potential cation channel protein 6 (TRPC6) in podocyte injury upregulates intracellular Ca2+ influx and stimulates Ca2+-dependent protease calpain-1 signaling. The traditional Chinese drug, tetrandrine, a nonselective Ca2+ channel blocker, has long been used to treat chronic kidney disease. This research aimed to explore the possible mechanisms underlying the anti-proteinuric properties of tetrandrine.MethodsWe investigated the involvement of tetrandrine in Ca2+ dependent calpain-1 signaling in mouse podocytes and adriamycin-induced nephropathy rats. Cyclosporine A (CsA) and U73122 were used as positive controls. Cell viability, cytotoxicity, Ca2+ concentration, calpain activity, and mRNA and protein expression levels of calpain-1 signaling pathways were examined. The clinical and pathological changes were measured.ResultsTetrandrine decreased intracellular Ca2+ influx in cultured TRPC6-overexpressing podocytes. In both in vitro and in vivo studies, the administration of tetrandrine downregulated calpain activity and the expression of calpain-1 and restored the expression of downstream Talin-1 and nephrin. Compared to CsA, tetrandrine treatment exhibited superior inhibitory effects on calpain activity and calpain-1 expression.ConclusionsTetrandrine has therapeutic potential in podocyte damage by blocking Ca2+-dependent activation of the calpain-1 signaling pathway. Tetrandrine reduced proteinuria, improved renal function, and alleviate renal pathological damage.

Isoliquiritigenin attenuates acute renal injury through suppressing oxidative stress, fibrosis and JAK2/STAT3 pathway in streptozotocin-induced diabetic rats

ABSTRACT The aim of the current study was to evaluate the protective effects and mechanisms of isoliquiritigenin (ISO) on acute renal injury. CCK-8 assays were applied to assess the effects of ISO at different doses (20, 40, and 80 μg/mL) on oxidative damage in human renal HK-2 cells incubated with high glucose. After the diabetic nephropathy (DN) rat model was established, the model animals were randomly assigned to saline-treated control, three model groups received the 10, 20 and 40 mg/kg ISO, respectively, using the healthy Sprague-Dawley (SD) rats as normal control. The blood biochemical indexes, renal functions, oxidative stress, morphological changes, fibrosis- and JAK2/STAT3-related factors in DN model rats were all assessed. The cellular viability of the renal HK-2 cells with oxidative damages were all markedly ameliorated via the incubation of ISO between 10 and 80 μg/mL compared with negative control. In addition, the significantly down-regulated ROS content and up-regulated expression levels of GSH, SOD2, and GPX1 were all observed in ISO-treated groups. Long-term administration of ISO at different doses in DN rats effectively improved general diabetic characteristics and renal morphology. Furthermore, long-term administration of ISO could ameliorate excessive oxidation stress, down-regulate the expression levels of renal fibrosis- and inflammation-related factors, as well as inhibit the JAK2/STAT3 signaling pathway. In conclusion, ISO at all three dosages could efficiently improve the renal injury induced by STZ via ameliorating renal fibrosis, oxidative stress, and inhibiting JAK2/STAT3 signaling pathways in the DN rats.

The Feasibility of Targeted Magnetic Iron Oxide Nanoagent for Noninvasive IgA Nephropathy Diagnosis.

IgA nephropathy is the most common glomerular disease in the world and has become a serious threat to human health. Accurate and non-invasive molecular imaging to detect and recognize the IgA nephropathy is critical for the subsequent timely treatment; otherwise, it may progress to end-stage renal disease and lead to glomerular dysfunction. In this study, we have developed a sensitive, specific, and biocompatible integrin αvβ3-targeted superparamagnetic Fe3O4 nanoparticles (NPs) for the noninvasive magnetic resonance imaging (MRI) of integrin αvβ3, which is overexpressed in glomerular mesangial region of IgA nephropathy. The rat model of IgA nephropathy was successfully established and verified by biochemical tests and histological staining. Meanwhile, the clinical 18F-AlF-NOTA-PRGD2 probe molecule was utilized to visualize and further confirmed the IgA nephropathy in vivo via positron emission computed tomography. Subsequently, the Fe3O4 NPs were conjugated with arginine–glycine–aspartic acid (RGD) molecules (Fe3O4-RGD), and their integrin αvβ3-targeted T2-weighted imaging (T2WI) potential has been carefully evaluated. The Fe3O4-RGD demonstrated great relaxation in vivo. The T2WI signal of renal layers in the targeted group at 3 h after intravenous injection of Fe3O4-RGD was distinctly lower than baseline, indicating MRI signal decreased in the established IgA nephropathy rat model. Moreover, the TEM characterization and Prussian blue staining confirmed that the Fe3O4-RGD was located at the region of glomerulus and tubular interstitium. Moreover, no obvious signal decreased was detected in the untargeted Fe3O4 treated and normal groups. Collectively, our results establish the possibility of Fe3O4-RGD serving as a feasible MRI agent for the noninvasive diagnosis of IgA nephropathy.

Efficacy of Modified Huangqi Chifeng decoction in alleviating renal fibrosis in rats with IgA nephropathy by inhibiting the TGF-β1/Smad3 signaling pathway through exosome regulation

IgA nephropathy is the most common form of primary glomerulonephritis and is a major cause of renal failure worldwide. Modified Huangqi Chifeng decoction (MHCD), a traditional Chinese herbal preparation, has clinical efficacy in reducing the 24-h urine protein levels in patients with IgA nephropathy. However, the molecular mechanism of MHCD needs further study. This study aimed to investigate the mechanisms by which MHCD treatment alleviates renal fibrosis. An IgA nephropathy rat model was established using bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. The rats were divided into control, model, telmisartan, low-dose MHCD, medium-dose MHCD, and high-dose MHCD groups. Treatments were administered to these groups for 8 weeks. Subsequently, the 24-h urine protein, serum creatinine, blood urea nitrogen, and blood albumin levels were measured. Pathological changes and degree of fibrosis in renal tissues were observed, and levels of the transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway components in renal tissues and TGF-β1 in urinary exosomes were measured. Telmisartan and MHCD reduced 24-h urine protein levels, alleviated renal pathological injury, and decreased the renal expression of fibronectin, laminin, and collagen IV in rats with IgA nephropathy. Urinary exosomes were extracted and identified for further investigation of their role in renal fibrosis. MHCD reduced TGF-β1 expression in urinary exosomes and reduced TGF-β1 and p-Smad3 levels in renal tissues. MHCD alleviated renal fibrosis in rats with IgA nephropathy by inhibiting the TGF-β1/Smad3 signaling pathway through the downregulation of TGF-β1 expression in exosomes.

Effects of Andrographis paniculata (Burm. F.) Extract on Diabetic Nephropathy in Rats.

Hyperglycemia and accumulation of advanced glycation end products (AGEs) play a significant role in the development of diabetic nephropathy. Andrographis paniculata (AP) is a plant with high flavonoid content with the potential to suppress oxidative stress activity in cells and tissue. This study was aimed to investigate the role of Andrographis paniculata extract (APE) in protecting kidney damage due to the formation of AGEs in the renal glomerulus in diabetic rats. A total of 30 male Sprague Dawley rats were randomly divided into five groups as follows: normal control group, streptozocin (STZ) induced diabetic group, STZ-induced diabetic group with AP extract (100 mg/kg BW), STZ-induced diabetic rats with AP extract (200 mg/kg BW), and STZ-induced diabetic rats with APE (400 mg/ kg BW). Blood glucose levels were measured before treatment and after treatment. Serum and urine parameters were determined. Antioxidant enzymes and lipid peroxide levels were determined in the kidney along with histopathological examination. The finding of this study showed that treatment APE at the dose of 200 mg/kg and 400 mg/kg ameliorated kidney hypertrophy index. SOD, catalase, and GSH activities significantly decreased in the kidney of STZ-diabetic rats compared to the normal control rats. Treatment with APE significantly decreased malondialdehyde level at the dose of 200 and 400 mg/kg BW. This study revealed evidence for improving diabetic retinopathy in male rats treated with Andrographis paniculata extract. APE significantly decreased oxidative stress activities in kidney of diabetic rats.

Protective effect of miR-146 against kidney injury in diabetic nephropathy rats through mediating the NF-κB signaling pathway.

The article "Protective effect of miR-146 against kidney injury in diabetic nephropathy rats through mediating the NF-κB signaling pathway", H.-Y. Yu, L.-F. Meng, X.-H. Lu, L.-H. Liu, X. Ci, Z. Zhuo, published in Eur Rev Med Pharmacol Sci 2020; 24 (6): 3215-3222-DOI: 10.26355/eurrev_202003_20688-PMID: 32271439, has been retracted by the authors due to some inaccuracies (some data cannot be repeated by further research). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20688.

Therapeutic role of Azadirachta indica leaves ethanolic extract against diabetic nephropathy in rats neonatally induced by streptozotocin

ABSTRACT Diabetic nephropathy (DN) is manifested by chronic loss of renal function due to damage of glomeruli and renal tubules. Therefore, this study is mainly designed to evaluate the therapeutic role of Azadiracta indica (neem) leaves extract as a novel approach for treatment of DN in rats neonatally induced by streptozotocin (STZ). For this study, 40 offspring were selected after parturition and categorized into four groups (n = 10). Group1: control group, group 2: neem leaves extract supplemented group, group 3: diabetic group that injected with a single dose of STZ and group 4: diabetic group treated with neem extract. The results revealed deleterious histological and ultrstructural changes in the renal tissues of diabetic rats. Such changes included atrophied glomeruli, dilated renal cortical tubules and scattered hemorrhage spots, thickening of glomerular basement membrane, expansion of mesangial matrix and pyknotic podocyte. Additionally, the proximal convoluted tubule and distal tubule showed cytoplasmic vacuolation, vacuolated mitochondria, scattered lipid droplets, lost microvilli and disrupted basal lamina and basal infoldings. Moreover, significant decreased levels of serum antioxidants (SOD&CAT) and significant increased levels of serum MDA, urea and creatinine were noticed in diabetic rats. Neem leaves extract successfully alleviated the histological and ultrastructural as well as biochemical changes induced by diabetes.

Biochanin-A has antidiabetic, antihyperlipidemic, antioxidant, and protective effects on diabetic nephropathy via suppression of TGF-β1 and PAR-2 genes expression in kidney tissues of STZ-induced diabetic rats.

One of the major complications of diabetes is diabetic nephropathy, and often many patients suffer from diabetic nephropathy. That is why it is important to find the mechanisms that cause nephropathy and its treatment. This study was designed to examine the antidiabetic effects of biochanin A (BCA) and evaluate its effects on oxidative stress markers and the expression of transforming growth factor-β1 (TGF-β1) and protease-activated receptors-2 (PAR-2) genes in the kidney of type 1 diabetic rats. After induction of diabetes using streptozotocin (STZ), 55 mg/kg bw dose, rats were randomly divided into four groups with six rats in each group as follows: normal group: normal control receiving normal saline and a single dose of citrate buffer daily; diabetic control group: diabetic control receiving 0.5% dimethyl sulfoxide daily; diabetic+BCA (10 mg/kg) group: diabetic rats receiving biochanin A at a dose of 10 mg/kg bw daily; diabetic+BCA (15 mg/kg) group: diabetic rats receiving biochanin A at a dose of 15 mg/kg bw daily. TGF-β1 and PAR-2 gene expression was assessed by real-time. Spectrophotometric methods were used to measure biochemical factors: fast blood glucose (FBG), urea, creatinine, albumin, lipids profiles malondialdehyde (MDA), and superoxide dismutase (SOD). The course of treatment in this study was 42 days. The results showed that in the diabetic control group, FBG, serum urea, creatinine, expression of TGF-β1 and PAR-2 genes, and the levels of MDA in kidney tissue significantly increased and SOD activity in kidney tissue and serum albumin significantly decreased compared to the normal group (p < 0.001). The results showed that administration of biochanin A (10 and 15 mg/kg) after 42 days significantly reduced the expression of TGF-β1 and PAR-2 genes and FBG, urea, creatinine in serum compared to the diabetic control group (p < 0.001), also significantly increased serum albumin compared to the diabetic control group (p < 0.001). The level of MDA and SOD activity in the tissues of diabetic rats that used biochanin A (10 and 15 mg/kg) was significantly reduced and increased, respectively, compared to the diabetic control group (p < 0.001). Also, the result showed that in the diabetic control group lipids profiles significantly is disturbed compared to the normal group (p < 0.001), the results also showed that biochanin A (10 and 15 mg/kg) administration could significantly improved the lipids profile compared to the control diabetic group (p < 0.001). It is noteworthy that it was found that the beneficial effects of the biochanin A were dose dependent. In conclusion, administration of biochanin A for 42 days has beneficial effect and improves diabetes and nephropathy in diabetic rats. So probably biochanin A can be used as an adjunct therapy in the treatment of diabetes.

The Protective Effect of Ethyl Acetate and n-Butanol Fractions of Wine-Steamed Ligustri Lucidi Fructus on Diabetic Nephropathy in Rats.

Ligustri Lucidi Fructus (LLF), the dry and ripe fruit of Ligustrum lucidum W. T. Aiton (Oleaceae), is a traditional Chinese medicine for nourishing the liver and kidney in clinics for thousands of years. Wine-steamed Ligustri Lucidi Fructus (WLL) can alleviate coolness and smoothness of LLF and enhance the function of nourishing the liver and kidney, so ancient and modern medicine usually used it in clinics. First of all, we prepared the extracts of different polar fractions of WLL to explore the effective fractions and potential mechanisms of WLL in the treatment of diabetic nephropathy (DN). Then, HPLC method was used to determine the contents of 12 active components in WLL and its different polar components. Finally, the potential relationship between 12 active components and physicochemical parameters of DN rats was explored. The pharmacological experiments showed that WLL, ethyl acetate (EtOAc), and n-butanol (n-BuOH) extracts not only significantly alleviated the clinical symptoms and kidney damage of DN rats but also had obvious anti-inflammatory and antioxidant effects. In addition, the results of HPLC analysis showed that the 12 active components of WLL mainly existed in the extracts of EtOAc and n-BuOH. The Pearson correlation analysis showed 12 active components and physicochemical parameters had different degrees of correlation. In conclusion, we proved that the extracts of EtOAc and n-BuOH were the effective fractions of WLL in treating DN in rats, and they could regulate the levels of inflammatory cytokines and decrease oxidation stress, which provides a basis for further research on the mechanism of WLL in treating DN and provides a pharmacological and chemical foundation for the development of new anti-DN drugs.

Therapeutic activity of sarpogrelate and dopamine D2 receptor agonists on cardiovascular and renal systems in rats with alloxan-induced diabetes

BackgroundDopamine D2 receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation was found between the initiation of myocardial injury ailment and long term treatment with dopamine D2 agonist drugs identified with the partial activation of 5-hydroxytryptamine receptor 2 A (5-HT2A). The investigation aimed to examine the activity of sarpogrelate (a 5-HT2A receptor blocker) in reducing myocardial injury prompted by extended haul utilisation of D2 receptor agonists in rats with alloxan-induced diabetes.MethodsBoth bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Both tail-cuff blood pressure and the BGL were recorded weekly. For all animals, the kidney hypertrophy index, serum creatinine, blood urea nitrogen, alanine transaminase, and aspartate transaminase levels were measured after one month of treatment. The severity of the cardiac injury was assessed by the estimation of lactate dehydrogenase-1 (LDH-1), cardiac troponin I, and tumor necrosis factor alpha 1 (TNF1). The triphenyltetrazolium chloride (TTC) staining method was used to determine the experimental myocardial infarction (MI) size.ResultsBromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine and cabergoline, alone, or in combination with sarpogrelate fundamentally diminished the blood concentrations of alkaline phosphatase (ALP), Aspartate aminotransferase (AST), urea, and creatinine. Bromocriptine and cabergoline alone showed a noteworthy increase in the LDH-1, Troponin I, and TNF1 levels in the serum (p < 0.05). Paradoxically, utilising bromocriptine or cabergoline with sarpogrelate treatment altogether decreased the levels of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed through the TTC staining method.ConclusionsThe examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these two drugs on the myocardial tissues.

Sunkist Peel Ethanol Extract Ameliorates Diabetic Nephropathy in Streptozotocin-Induced Diabetic Wistar Rats

Background: Kidney disorders in diabetic patients can gradually fall into end-stage kidney disease (ESKD) which can greatly interfere with the person's quality of life, in developed countries about 50% of patients with ESKD are caused by diabetes. On the other hand, various studies on citrus fruits have been performed to explore its pharmacological benefits.&#x0D; Aim: this study was aimed to explore the benefits of Sunkist orange peel ethanol extract against diabetic nephropathy in wistar rats as animals’ trial.&#x0D; Methods: This study was used 25 rats and was divided into five groups: viz. control, standard, Sunkist Peel Ethanol Extract-I, II, and III (500, 750, and 1500 mg/kg BW). After 28 days of intervention, BUN and Creatinine levels were measured in all rats. Meanwhile, data analysis used is parametric statistics in the form of One-Way ANOVA with alternative analysis in the form of the Kruskal Wallis test.&#x0D; Results: This study showed that the Sunkist peels ethanol extract significantly decreased BUN (P-Value &lt; 0.05) and creatinine (P-Value &lt; 0.05) level. The highest dosage of extract did not show a significant difference in BUN level against standard group.&#x0D; Conclusion: Overall, it can be concluded that the Sunkist peel ethanol extract has kidney protection effect against diabetic nephropathy at highest dosage (1500 mg/ kg BW).

Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models.

Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.

Ultra-Performance Liquid Chromatography-Q-Exactive Orbitrap-Mass Spectrometry Analysis for Metabolic Communication between Heart and Kidney in Adriamycin-Induced Nephropathy Rats

Background/Aims: Although the adriamycin-induced nephropathy model is frequently employed in the study of nephrotic syndrome and focal segmental glomerulosclerosis, the accompanying myocardial damage has always been a cause for concern. Therefore, there is a great need to study cardiorenal communication in this model. Methods: An adriamycin-induced nephropathy model was established via tail vein injection. The levels of the biochemical indicators serum albumin, serum globulin, serum total protein, serum cholesterol, serum creatinine (SCr), urinary protein, and urinary creatinine (UCr) were measured, and histopathological changes in the heart and kidneys were assessed using hematoxylin-eosin staining. Metabolomic changes in the heart, blood, and kidneys were analyzed using the metabolomics method based on ultra-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry. Results: Compared with the control group, the model group showed significant decreases in serum protein and total protein levels, albumin/globulin ratio, and creatinine clearance rate as well as significant increases in serum cholesterol, SCr, urinary protein, and UCr levels. Significant pathological changes were observed in the renal pathology sections in the model group, including diffusely merged glomerular epithelial cells, inflammatory infiltration, and vacuolated glomerular cells. Additionally, thickened myocardial fibers, swollen nuclei, inflammatory infiltration, and partial myocardial necrosis could be seen in the cardiac pathology sections in the model group. Based on multivariate statistical analysis, a total of 20 differential metabolites associated with 15 metabolic pathways were identified in the heart, 7 differential metabolites with 7 metabolic pathways were identified in the blood, and 16 differential metabolites with 21 metabolic pathways were identified in the kidney. Moreover, 6 common metabolic pathways shared by the heart and kidney were identified: arginine and proline metabolism; arginine biosynthesis; glutathione metabolism; alanine, aspartate, and glutamate metabolism; beta-alanine metabolism; and histidine metabolism. Among these metabolic pathways, alanine, aspartate, and glutamate metabolism was shared by the heart, blood, and kidney. Succinic acid was found to be the key regulatory metabolite in cardiorenal metabolic communication. Conclusion: Six metabolic pathways were found to be involved in cardiorenal metabolic communication in an adriamycin-induced nephropathy model, in which alanine, aspartate, and glutamate metabolism may be the metabolic link between the heart and kidney in the development and maintenance of oxidative stress and inflammation. Succinic acid may serve as a key regulatory metabolic switch or marker of cardiac and renal co-injury, as shown in an adriamycin-induced nephropathy model.

Confounders for kidney carcinogenesis in rodent cancer bioassays.

In the long-term safety testing of chemicals for carcinogenicity the toxicologist needs to be aware of a number of scenarios where renal tubule tumors, or their precursors, arise that are not due to a carcinogenic action of the test article. Situations producing false positive results in the kidney include exacerbation of chronic progressive nephropathy (CPN) in rats, confusion of atypical tubule hyperplasia (the obligate precursor of renal tubule tumor) with foci of benign CPN-related renal tubule cell proliferation, inclusion of spontaneous tumor entities, such as the amphophilic-vacuolar tumor, in the test article tumor count, the possibility of a link between spontaneous forms of tubule dilatation and renal tubule tumor formation in mice, and the supposed predictivity of chemically-induced karyomegaly for renal carcinogenicity in both rats and mice. Examples of these misleading situations are described and discussed.

Icariin inhibits epithelial mesenchymal transition of renal tubular epithelial cells via regulating the miR-122-5p/FOXP2 axis in diabetic nephropathy rats

Epithelial mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs) dominates the pathology of diabetic nephropathy (DN). microRNAs (miRNAs) can influence the fate of DN via regulation of EMT. This study aimed to analyze the role of Icariin (ICA) in EMT of RTECs, hoping to provide theoretical basis for DN management. The DN rat model was established using streptozocin, followed by ICA treatment, histopathological observation, and detection of creatinine and blood urea nitrogen. In vitro cell models were established using high glucose (HG), followed by assessment of cell proliferation, apoptosis, and migration, and E-cadherin, α-SMA, miR-122-5p, and FOXP2 expressions. Cells were transfected with miR-122-5p mimics or si-FOXP2 for joint experiments with ICA. The targeting relationship between miR-122-5p and FOXP2 was verified. ICA repaired renal dysfunctions and glomerular structure abnormities of DN rats in a dose-dependent manner. In vitro, ICA improved proliferation while suppressed migration, apoptosis, and EMT of RTECs. miR-122-5p was up-regulated in DN rats and suppressed by ICA, and miR-122-5p targeted FOXP2. miR-122-5p up-regulation or FOXP2 down-regulation reversed the protective effects of ICA on HG-induced RTECs. Overall, our finding ascertained that ICA inhibited miR-122-5p to promote FOXP2 transcription, thereby attenuating EMT of RTECs and renal injury in DN rats.

P-Coumaric acid attenuates high-fat diet-induced oxidative stress and nephropathy in diabetic rats.

The prevalence of persistent hyperglycaemia during diabetes, impair antioxidant defence system and generate reactive oxygen species, which majorly contribute to its progression and associated complications. Phytochemicals were suggested to scavenge-free radicals and exert antioxidant effects required to improve insulin sensitivity and reduce the occurrence of diabetes-associated complications. We hypothesise that a phenolic phytochemical p-coumaric can reduce diabetes-induced oxidative stress and improve diabetes-associated nephropathy in rats. The aim of this study is to analyse the protective effects of p-coumaric acid against diabetes-induced oxidative stress and nephropathy in high-fat diet-induced diabetic rats. The oral feeding of p-coumaric acid (20mg/kg for 12weeks) was found to significantly decrease the elevated levels of blood glucose in high-fat diet-induced type 2 diabetic rats. p-Coumaric acid treatment also decreases the kidney weight whilst increasing the total body weight of diabetic rats. Furthermore whilst evaluation of the different renal functioning tests, p-coumaric acid significantly improves histopathological changes and the levels of urea, creatinine and uric acid in serum of diabetic rats, which was otherwise elevated under diabetic conditions. Our results also highlight that p-coumaric acid is an efficient compound with antioxidant properties and improves the diabetes-induced change in lipid peroxidation and activities of antioxidant enzymes: catalase, glutathione-S-transferase and superoxide dismutase. p-Coumaric acid thus possesses the potential to prevent diabetic nephropathy by reducing oxidative stress and can thus serve as a potential drug target for pharmaceutical companies.

Tangshenping granule inhibits pyroptosis in a rat model of streptozotocin-induced diabetic nephropathy via the NLRP3/caspase-1/GSDMD pathway

To explore the inhibitory effect of Tangshenping (TSP) on pyroptosis in a streptozotocin-induced diabetic nephropathy (DN) rat model. DN was established in Sprague–Dawley rats. Rats were randomly divided into DN (model group), irbesartan, and TSP low-, medium-, and high-dose groups, besides the control group. The 24 h albuminuria content, and serum content of TC, TGs, Scr, IL-1β, UREA, LDLs, and IL-18 were assessed. Hematoxylin & eosin and Mallory staining were performed to examine pathological changes in the kidney. The mRNA and protein expression of NLRP3, caspase 1, and GSDMD in the kidney were also examined. The 24 h albuminuria content was obviously lower in the treatment groups compared to the model group (all P < .01). Levels of TC, TGs, Scr, UREA, LDLs, and IL-18 after drug interventions were obviously lower compared to the model group (all P < .05). The serum content of IL-1β in the TSP medium- and high-dose groups were much lower compared to the model group ( P = .013 and P = .001, respectively). Through immunohistochemistry and western blotting, we observed that the protein expressions of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 were lower after drug interventions compared to the model group (all P < .05). Using qPCR, we observed that the mRNA expressions of caspase-1, IL-1β, IL-18, and GSDMD after drug interventions were significantly lower compared to the model group (all P < .05). The mRNA expressions of NLRP3 in the TSP medium- and high-dose groups were both lower compared to the model group (all P < .05). TSP downregulated mRNA and protein expressions of NLRP3, caspase-1, and GSDMD. Our findings demonstrate that the beneficial effects of TSP on renal function are at least partly mediated by the inhibition of micro-inflammation and modulation of the expression of pyroptosis-related factors.

Detecting apoptosis signal-regulating kinase 1 protein expression in diabetica nephropathy rats using magnetic hydrophilic nanomaterials

Apoptosis signal-regulating kinase 1 (ASK1) signaling is involved in the occurrence and progression of diabetic nephropathy (DN) renal fibrosis, yet the detection of ASK1 requires further investigation. To explore the effect of magnetic nanomaterials combined with ASK1 signaling on renal fibrosis, a DN rat model was generated. Thirty Wistar rats were randomly allocated into three experimental models: control, sham-operated, and DN model groups. Concentrations of postoperative serum creatinine (Scr) and blood urea nitrogen (BUN) were measured to determine the success of the DN model group. Chitosan coated magnetic hydrophilic nanomaterials (Fe3O4@CS MCNCs) were prepared by a “one-pot reaction” method, and further characterized to assess their protein adsorption properties. ASK1 protein expression was analyzed by combining conventional immunohistochemistry and Western blotting techniques with the magnetic nanomaterials. Serum Scr and BUN levels in the DN model group were significantly increased (P &lt; 0.01), indicating that the model was successfully generated. Fe3O4@CS MCNCs were characterized and demonstrated effective hydrophilicity, magnetism, and protein adsorption capacity, highlighting its potential application in proteomic research. The detection of ASK1 protein expression was consistent with that of immunohistochemistry and Western blotting when using the magnetic nanomaterials. Furthermore, ASK1 protein expression in the DN model group was significantly increased compared with the control and sham-operated groups. In this study, magnetic hydrophilic nanomaterials were demonstrated to be feasible for protein detection. In addition, the results indicated the potential involvement of ASK1 signaling in the process of renal fibrosis in DN rats.

Revealing the Antifibrotic Mechanism of Finerenone in the DOCA-Salt Nephropathy Rat Model Using Single Nuclei and Bulk Transcriptomics

Revealing the Antifibrotic Mechanism of Finerenone in the DOCA-Salt Nephropathy Rat Model Using Single Nuclei and Bulk Transcriptomics