Symptoms Of Diabetic Nephropathy Research Articles

Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy.

Diabetic nephropathy (DN) presents a significant public health challenge due to its high rate of incidence and severe health consequences. Renalase has been identified as having renal-protective properties. A key contributor to albuminuria in DN patients is podocyte loss. The function of Renalase in DN in relation to podocyte activity needs to be explored further. In this study, we assessed the therapeutic efficacy of Renalase by monitoring changes in urine protein levels and podocyte health in db/db mice. We also induced hyperglycemia (HG) to stimulate podocyte clone 5 (MPC5) cells to create a model of podocyte loss in DN. Through co-culturing these cells with Renalase or H2O2, we investigated the process by which Renalase prevents podocyte loss in vitro. In db/db mice, Renalase expression was significantly reduced, and adenoviral-mediated Renalase expression markedly alleviated DN symptoms and proteinuria. Furthermore, podocytopathy in db/db mice was significantly mitigated. In vitro, Renalase improved the expression of podocyte marker proteins, podocin, and nephrin, which are reduced by HG, as well as decreased oxidative stress and restrained apoptosis. Our findings suggest that Renalase can mitigate DN by reducing proteinuria through podocyte protection, potentially by inhibiting oxidative stress and apoptosis. These data suggest that Renalase may serve as a novel therapeutic agent in suppressing DN.

Germacrone protects renal tubular cells against ferroptotic death and ROS release by re-activating mitophagy in diabetic nephropathy

Mitophagy is a critical intracellular event during the progression of diabetic nephropathy (DN). Our previous study demonstrated that germacrone has anti-ferroptotic properties and is a potential therapeutic agent for DN. However, the relationship among germacrone, mitophagy, and ferroptosis in DN remains unclear. In this study, the data confirmed that germacrone ameliorates high glucose (HG)-induced ferroptosis through limiting Fe (2+) content and lipid reactive oxygen species (ROS) accumulation in human kidney 2 (HK-2) cells. Germacrone reversed HG-mediated inhibition of mitophagy. Mitophagy inhibition and anabatic mitochondrial ROS abrogate germacrone-mediated protective effects against ferroptotic death, resulting in the subsequent activation of mitochondrial DNA (mtDNA) cytosolic leakage-induced stimulator of interferon response CGAMP interactor 1 (STING) signaling. The combination of a mitochondrial ROS antagonist and germacrone acts synergistically to alleviate the ferroptotic death of tubular cells and DN symptoms. In summary, germacrone ameliorated ferroptotic death in tubular cells by reactivating mitophagy and inhibiting mtDNA-STING signaling in DN. This study provides a novel insight into germacrone-mediated protection against DN progression and further confirms that antioxidant pharmacological strategies facilitate the treatment of DN.

Probiotic Formula Ameliorates Renal Dysfunction Indicators, Glycemic Levels, and Blood Pressure in a Diabetic Nephropathy Mouse Model.

One-third of patients with end-stage chronic kidney disease (CKD) experience diabetic nephropathy (DN), which worsens the progression of renal dysfunction. However, preventive measures for DN are lacking. Lactobacillus acidophilus TYCA06, Bifidobacterium longum subsp. infantis BLI-02, and Bifidobacterium bifidum VDD088 probiotic strains have been demonstrated to delay CKD progression. This study evaluated their biological functions to stabilize blood-glucose fluctuations and delay the deterioration of renal function. The db/db mice were used to establish a DN animal model. This was supplemented with 5.125 × 109 CFU/kg/day (high dose) or 1.025 × 109 CFU/kg/day (low dose) mixed with probiotics containing TYCA06, BLI-02, and VDD088 for 8 weeks. Blood urea nitrogen (BUN), serum creatinine, blood glucose, and urine protein were analyzed. Possible mechanisms underlying the alleviation of DN symptoms by probiotic strains were evaluated through in vitro tests. Animal experiments revealed that BUN, serum creatinine, and blood glucose upon probiotic administration were significantly lower than in the control group. The rate of change of urine protein decreased significantly, and blood pressure, glucose tolerance, and renal fibrosis were improved. In vitro testing indicated that TYCA06 and BLI-02 significantly increased acetic acid concentration. TYCA06, BLI-02, and VDD088 were associated with better antioxidation, anti-inflammation, and glucose consumption activities relative to the control. A combination of the probiotics TYCA06, BLI-02, and VDD088 attenuated renal function deterioration and improved blood-glucose fluctuation in a diabetes-induced CKD mouse model.

Tripartite motif containing 23 functions as a critical regulator in macrophages to control the pathological feature of diabetic nephropathy.

Diabetic nephropathy (DN) is a kidney disease resulting from diabetes. Macrophages and macrophage-mediated inflammation contributed to the development of DN. Tripartite motif containing 23 (TRIM23) is E3 ligase and has been involved in inflammation. Until now, the precise roles of TRIM23 in DN are not described yet. Therefore, we evaluated the functions of TRIM23 in DN. We generated mice with TRIM23 deficiency in macrophages. We also established diabetic mice model. The expression of TRIM23 was measured in diabetic animals. The DN symptoms were compared between diabetic wild-type (WT) mice and TRIM23 conditional knock out mice. The cytokine expression, ubiquitination of TAB2, and interactions between TAB2 and IKK were compared in oxidized low-density lipoprotein (oxLDL) or lipopolysaccharides (LPS)-treated WT and TRIM23-deficient macrophages. Upregulation of TRIM23 was observed in diabetic mice and LPS or oxLDL-treated macrophages. Diabetic mice with TRIM23 deficiency in macrophages had attenuated DN symptoms. TRIM23-deficient macrophages had decreased pro-inflammatory cytokines production after oxLDL or LPS stimulation. TRIM23 was predicted to interact with TAB2. The ubiquitination of TAB2 was abolished in oxLDL-treated TRIM23-deficient macrophages, which correlated with decreased activation of IKK. TRIM23 regulates inflammation in macrophages and plays important role in DN.

Management of Diabetes Mellitus, Risk Factors and Complications

Chronic progressive metabolic problem and chronic hyperglycemia caused by a dysregulation of protein, lipid, and carbohydrate metabolism are two symptoms of diabetes mellitus, a complicated condition. Verapamil belongs to a group of calcium channel blockers that are not dihydropyridines. It works by preventing calcium from entering beta cells' cytoplasm, preventing the second phase of insulin release driven by glucose, as well as sulfonylurea and glucagon. Nephropathy, neuropathy, and retinopathy are examples of microvascular consequences of diabetes mellitus (cardiovascular and cerebrovascular disease). In both kinds of diabetes mellitus, higher urine albumin excretion (proteinuria) or decreased kidney glomerular filtration rate are symptoms of diabetic nephropathy, a microvascular consequence. By lowering patients' blood sugar levels and reducing their risk of cardiovascular disease, diabetes mellitus therapy aims to reduce mortality, delay the onset of disease complications, and slow the disease's progression. Metformin increases peripheral glucose utilization, liver, muscle, and adipose tissue sensitivity to insulin, inhibits gluconeogenesis, and reduces glucose absorption from the gastrointestinal system.

Mitogen-activating protein kinase kinase kinase kinase-3, inhibited by Astragaloside IV through H3 lysine 4 monomethylation, promotes the progression of diabetic nephropathy by inducing apoptosis

ABSTRACT Astragaloside IV (AS-IV) is a bioactive saponin extracted from the Astragalus root and has been reported to exert a protective effect on diabetic nephropathy (DN). However, the underlying mechanism remains unclear. Herein, we found that AS-IV treatment alleviated DN symptoms in DN mice accompanied by reduced metabolic parameters (body weight, urine microalbumin and creatinine, creatinine clearance, and serum urea nitrogen and creatinine), pathological changes, and apoptosis. Epigenetic histone modifications are closely related to diabetes and its complications, including H3 lysine 4 monomethylation (H3K4me1, a promoter of gene transcription). A ChIP-seq assay was conducted to identify the genes regulated by H3K4me1 in DN mice after AS-IV treatment and followed by a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The results showed that there were 16 common genes targeted by H3K4me1 in normal and AS-IV-treated DN mice, 1148 genes were targeted by H3K4me1 only in DN mice. From the 1148 genes, we screened mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) for the verification of gene expression and functional study. The results showed that MAP4K3 was significantly increased in DN mice and high glucose (HG)-treated NRK-52E cells, which was reversed by AS-IV. MAP4K3 silencing reduced the apoptosis of NRK-52E cells under HG condition, as evidenced by decreased cleaved caspase 3 and Bax (pro-apoptotic factors), and increased Bcl-2 and Bcl-xl (anti-apoptotic factors). Collectively, AS-IV may downregulate MAP4K3 expression by regulating H3K4me1 binding and further reducing apoptosis, which may be one of the potential mechanisms that AS-IV plays a protective effect on DN.

Effects of L-Carnitine Treatment on Kidney Mitochondria and Macrophages in Mice with Diabetic Nephropathy

Introduction: In diabetic nephropathy (DN), mitochondrial dysfunction and leakage of mitochondrial DNA (mtDNA) are caused by the downregulation of superoxide dismutase 2 (SOD2). mtDNA induces the activation of Toll-like receptor (TLR) 9, which is present in macrophages (Mφs), and triggers their activation. Methods: We orally administered L-carnitine, which exerts protective effects on the mitochondria, to obesity-induced DN (db/db) mice for 8 weeks. We then investigated the effects of L-carnitine on kidney mitochondrial reactive oxygen species (mtROS) production, circulating mtDNA content, and kidney CD11b^high/CD11b^low Mφ functions. Results: In db/db mice, mtROS production increased in proximal tubular cells and kidney CD11b^low Mφs; both Mφ types showed enhanced TLR9 expression. L-Carnitine treatment suppressed mtROS production in both proximal tubular cells and CD11b^low Mφs (p < 0.01), with improved SOD2 expression in the kidney (p < 0.01), decreased circulating mtDNA content, and reduced albuminuria. Moreover, it suppressed Mφ infiltration into kidneys and reduced TLR9 expression in Mφs (p < 0.01), thereby lowering tumor necrosis factor-α production in CD11b^high Mφs (p < 0.05) and ROS production by CD11b^low Mφs (p < 0.01). Collectively, these changes alleviated DN symptoms. Conclusion: The positive effects of L-carnitine on DN suggest its potential as a novel therapeutic agent against obesity-linked DN.

Fucoidan mitigated diabetic nephropathy through the downregulation of PKC and modulation of NF-κB signaling pathway: in vitro and in vivo investigations.

The persistence of hyperglycemia and oxidative stress in diabetic patients ultimately leads to diabetic nephropathy (DN). In this study, we investigated the effect of sulfated polysaccharides (SPS) extracted from Laminaria japonica in relieving DN symptoms. To induce the diabetic model, normal rats were kept on a high-sugar, high-fat diet, then they were injected with streptozocin. Groups of these rats were later treated with SPS and/or protein kinase C (PKC) inhibitor. The analyses performed herein demonstrate that although diabetes significantly decreases the body weights of rats, SPS and inhibitor treatments increase these weights, as well as the ratios of renal to total body weight. Serum biochemical analyses indicate that blood urea nitrogen and serum creatinine levels gradually decrease in the SPS group. In addition, DN symptoms are substantially relieved by SPS and/or inhibitor treatments, as evidenced by histopathological analyses. Changes in the expressions of PKC-α, PKC-β, P-selectin, nuclear factor kappa B (NF-κB), and p65, detected by immunohistochemistry and western blot assessments, show that SPS regulates diabetic nephropathy via the PKC/NF-κB pathway.

Investigation of the anti-diabetic nephropathy activity of puerarin

Puerarin has potential therapeutic effects on diabetic nephropathy (DN), but the effectiveness as a treatment for DN and the underlying mechanism remain to be elucidated. The DN-like model induced by high glucose in vitro and the DN model induced by streptozotocin in vivo were used to observe the effect of puerarin. The results showed that puerarin can enhance the activity of HBZY-1 cells and reduce apoptosis. in vivo enzymelinked immunosorbent assay and biochemical assay showed that puerarin can improve DN symptoms. Using hematoxylin and eosin staining to stain kidney tissues confirmed that puerarin has a protective effect on DN. Furthermore, puerarin can reduce the content of collagen type IV, laminin LN, tumor necrosis factor, p38, CREB, Fos, Jun, and MMP9 in HBZY-1 cells and DN rats. In conclusion, puerarin can effectively prevent apoptosis in vitro and improve DN-like symptoms by inhibiting the p38/MAPK signaling pathway in vivo. Therefore, puerarin has the potential to treat DN.

AN OPEN CLINICAL STUDY EVALUATING THE EFFECT OF SHILAJITHU LOHA RASAYANA ON AFFLICTION OF BASTI MARMA (DIABETIC NEPHROPATHY) IN PATIENTS WITH PRAMEHA

Objectives of the study include answer to the research question or to the hypothesis framed. Present study was conducted to evaluate the therapeutic effect of Shilajithu loha rasayana in reducing the affliction of Basti marma in patients with Prameha/diabetic nephropathy, also to evaluate the therapeutic effect of Shilajithu loha rasayana in reducing the blood sugar level in patients suffering from affliction of Basti marma in Prameha/diabetic nephropathy. Design: Study Type: Interventional, Estimated enrolment: 30 participants, Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Primary Purpose: Treatment, Masking: Open Label. Participants: From October 2019 to January 2020, 30 patients of affliction of Basthi marma in Prameha/ diabetic nephropathy having symptoms of diabetic nephropathy (microalbuminuria, reduced eGFR, raised cystatin-c) with a minimum of 5yrs history of diabetes are taken up for the study. Intervention: Kosta shodhana on day 1: 20ml of Eranda taila added with equal amount of Shunthi kashaya is orally administered during early morning in empty stomach. Day 2 to 22: Shilajithu loha rasayana is orally administered half an hour before breakfast, in a dose of 12g with warm water. Patient was advised diabetic diet and to do brisk walking/jogging or light exercise for 45 minutes daily during the course of treatment. Results: Shilajithu loha rasayana was successful in improving renal functions by increasing the glomerular filtration rate and reducing cystatin-c in patients also was successful in reducing fasting blood sugar and symptoms of Prameha which was justified statistically with p value &lt;0.001. Conclusion: Shilajithu loha rasayana was successful in increasing the renal function and reducing symptoms of Prameha.

Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial-Mesenchymal Transition of Podocytes by Inhibiting ZEB2.

Background Podocyte migration is actively involved in the process of podocyte loss and proteinuria production, which is closely associated with the development of diabetic nephropathy (DN). Exosomes from adipose-derived stem cells (ADSCs-Exos) effectively inhibit podocyte apoptosis in the treatment of DN. However, how ADSCs-Exos affect the migration of podocytes is obscure. This study is aimed at exploring the regulatory role of ADSCs-Exos on cell migration and the underlying mechanism. Methods ADSCs-Exo was authenticated by transmission electron microscopy (TEM), western blotting, and flow cytometry. Cell viability and migration ability of podocytes were measured by CCK8 and Transwell assays, respectively. Relative expressions of miRNAs and mRNAs were determined by qRT-PCR. The transmitting between PKH26-labeled exosome and podocytes was evaluated by IF assay. Dual luciferase reporter assay was employed to detect the relationship between miR-215-5p and ZEB2. Results The exposure to serum from DN patient (hDN-serum) significantly inhibited cell viability of podocytes, but ADSCs-Exo addition notably blunts cytotoxicity induced by the transient stimulus of hDN-serum. Besides, ADSCs-Exo administration powerfully impeded high glucose- (HG-) induced migration and injury of podocyte. With the podocyte dysfunction, several miRNAs presented a significant decline under the treatment of HG including miR-251-5p, miR-879-5p, miR-3066-5p, and miR-7a-5p, all of which were rescued by the addition of ADSCs-Exo. However, only miR-251-5p was a key determinant in the process of ADSCs-Exo-mediated protective role on podocyte damage. The miR-251-5p inhibitor counteracted the improvement from the ADSCs-Exo preparation on HG-induced proliferation inhibition and migration promotion. Additionally, miR-215-5p mimics alone remarkably reversed HG-induced EMT process of podocyte. Mechanistically, we confirmed that ADSCs-Exos mediated the shuttling of miR-215-5p to podocyte, thereby protecting against HG-induced metastasis, possibly through inhibiting the transcription of ZEB2. Conclusion ADSCs-Exo has the protective effect on HG-evoked EMT progression of podocytes thru a mechanism involving ZEB2. Potentially, the ADSCs-Exo preparation is a useful therapeutic strategy for improving podocyte dysfunction and DN symptoms clinically.

Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats

BackgroundAstragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS).MethodsDN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro.ResultsTreatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment.ConclusionsThese novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.

Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

Clinical studies have shown that hyperglycemia can induce early-stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial-mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)-induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF-β signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co-treatment of STZ-induced DN rats showed that glomerulosclerosis in early-stage DN was reversible (P < .05 compared with that in STZ-induced DM rats). The results of this study support early intervention in diabetes or DN as a more efficient therapeutic strategy.

4-O-methylhonokiol ameliorates type 2 diabetes-induced nephropathy in mice likely by activation of AMPK-mediated fatty acid oxidation and Nrf2-mediated anti-oxidative stress

Diabetic nephropathy (DN) is one of the most serious long-term complications of type 2 diabetes (T2D). 4-O-methylhonokiol (MH) is one of the biologically active ingredients extracted from the Magnolia stem bark. In this study, we aim to elucidate whether treatment with MH can ameliorate or slow-down progression of DN in a T2D murine model and, if so, whether the protective response of MH correlates with AMPK-associated anti-oxidant and anti-inflammatory effects. To induce T2D, mice were fed normal diet (ND) or high fat diet (HFD) for 3 months to induce insulin resistance, followed by an intraperitoneal injection of STZ to induce hyperglycemia. Both T2D and control mice received gavage containing vehicle or MH once diabetes onset for 3 months. Once completing 3-month MH treatment, five mice from each group were sacrificed as 3 month time-point. The rest mice in each group were sacrificed 3 months later as 6 month time-point. In T2D mice, the typical DN symptoms were induced as expected, reflected by increased proteinuria, renal lipid accumulation and lipotoxic effects inducing oxidative stress, and inflammatory reactions, and final fibrosis. However, these typical DN changes were significantly prevented by MH treatment for 3 months and even at 3 months post-MH withdrawal. Mechanistically, MH renal-protection from DN may be related to lipid metabolic improvement and oxidative stress attenuation along with increases in AMPK/PGC-1α/CPT1B-mediated fatty acid oxidation and Nrf2/SOD2-mediated anti-oxidative stress. Results showed the preventive effect of MH on the renal oxidative stress and inflammation in DN.

Upregulation of microRNA-424 relieved diabetic nephropathy by targeting Rictor through mTOR Complex2/Protein Kinase B signaling.

To investigate the role of miR-424 in diabetic nephropathy (DN) and its relationship with Rictor in mammalian target of rapamycin (mTOR) C2/Akt signaling. The western blot analysis and real-time polymerase chain reaction were used to determine the differential expression of Rictor, mTOR, and miR-424 in DN rats. The upregulation of miR-424 was achieved by caudal vein injection of miR-424 mimics. The renal lesion was evaluated by hematoxylin-eosin staining (H&E) and periodic acid schiff staining. The dual-luciferase reporter assay was conducted to determine the binding target of miR-424. The effect of miR-424 upregulation on apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated 2-Deoxyuridine-5-Triphosphate (dUTP) nick-end labeling assay and western blot analysis. A significantly lower expression of miR-424 and a significantly higher expression of Rictor and mTOR were found in renal tissues of DN rats. The upregulation of miR-424 improved renal lesion and DN symptoms of blood glucose level, urine protein level, body weight, creatinine level, blood urea nitrogen, and KW/BW ratio. The upregulation of miR-424 could significantly reduce apoptosis rates of tissue cells by decreasing the expression levels of caspase-3 and Bax as well as increasing the level of Bcl-2. Furthermore, Rictor was the direct target for miR-424, and upregulation of miR-424 inhibited Rictor through Akt signaling in renal tissue of DN rats and high-glucose-treated human glomerular mesangial cells. miR-424 contributes to alleviating the symptoms in DN rat models by targeting Rictor through mTORC2/Akt signaling.

Screening for diabetic nephropathy at diabetes clinic in Su-dan

Background: Diabetes mellitus and its complications are one of the major health problems in Sudan. Only few patients had been screened before their complications appeared. As a result of this, many patients have not been discovered and ended with late stages of the disease, and are now showing evidence of diabetic nephropathy. Objective: The main aim of this study is at discovering the factors in terms of patients knowledge that are leading to the defect in diabetic nephropathy screening at one of the diabetes clinics. Methods: This cross-sectional hospital-based descriptive study was conducted at University charity teaching hospital affiliated to University of Medical Sciences and Technology (UMST) and covered 56 patients diagnosed with Diabetes Mellitus during the period from August to October 2013. Information was obtained by direct interviewing of patients using a questionnaire, and filled in the form of an interview. Results: A total of 56 patients were included, their mean age group was 60-69 and of them 51.8% were males. Regarding awareness about the symptoms of diabetic nephropathy, the most known symptom was fatigue, known by 27 (48.2%). Out of all the participants 55 (98.2%) reported checking their blood pressure regularly. A total of 50 (89.2%) believed that smoking had a harmful effect on their diabetes and 12 (21.4%) participants smoke cigarettes. Regarding exercise (54, 96.4%) believed that exercise is helpful in decreasing the incidence of diabetic nephropathy, however only 16 (28.6%) participants reported exercising regularly. A total of 51 (91%) have heard about the screening for diabetic nephropathy yet only 46 (82.1%) participant had their screening done regularly. Conclusion: Majority of participants had an understanding of the factors and knowledge on the signs of diabetic nephropathy, yet not all have evaded the risk factors. Raising awareness is essential but providing facilities to ensure its compliance is required. Keywords: Diabetes Mellitus; Nephropathy.

Metabonomic analysis of the therapeutic effect of Zhibai Dihuang Pill in treatment of streptozotocin-induced diabetic nephropathy

Ethnopharmacological relevanceZhibai Dihuang Pill (ZDP) is one of ancient traditional Chinese medicines (TCMs), which is usually used for the treatment of kidney deficiency for thousands of years in China. Aim of the studyTraditional Chinese medicines (TCMs) usually operate in vivo through multi-components, multi-ways and multi-targets. However, the molecular mechanisms of TCMs remain unclear. In the present work, nuclear magnetic resonance (NMR)-based metabonomic analysis was used to evaluate the therapeutic effect of Zhibai Dihuang Pill (ZDP) on diabetic nephropathy (DN) rats induced by streptozotocin and to address the underlying molecular mechanism. Materials and methodsMale rats were divided into three groups: control, DN and ZDP-treated DN (ZDP-DN), respectively. Based on 1H NMR spectra of sera, urine and kidney extracts from the rats, principle component analysis (PCA) was performed to identify different metabolic profiles. Kidney portions and serum and urine samples were also subjected to histopathological or biochemical examination. ResultsPCA scores plots demonstrate that the cluster of DN rats is separated from that of control rats, while some of ZDP-DN rats are located close to control rats, indicating that metabolic profiles of these ZDP-DN rats are restored toward those of control rats. Our results illustrate that ZDP treatment could lower the levels of lipids and 3-hydrobutyrate, and raise the level of lactate in sera of DN rats. Moreover, ZDP treatment could also reduce the levels of glucose, 3-hydrobutyrate and lactate, enhance the level of betaine in kidney tissues. ConclusionOur study indicates that ZDP treatment can ameliorate DN symptoms by intervening in some dominating metabolic pathways, such as inhibiting glucose and lipid metabolism, enhancing methylamine metabolism. Our work may be of benefit to both evaluation of the therapeutic effect of TCM and elucidation of the underlying molecular mechanism.

Treatment of diabetic nephropathy with acupuncture

to observe the clinical efficacy of acupuncture on diabetic nephropathy. altogether 54 cases were randomly allocated into acupuncture group (30 cases) and control group of western medications (24 cases), the latter was treated with routine western medication, while the former was combined acupuncture based on routine western medication, and the treatment course of the two groups were both 30 days. the effect of treatment group was superior to the control group (P<0.05). acupuncture can improve symptoms of diabetic nephropathy, lower blood glucose, urine albumin, blood urine nitrogen and creatinine and improve the function of kidney.

Effects of prostacyclin in treatment of diabetic nephropathy in rats

Microvascular complications, and primarily diabetic nephropathy, are one of the most severe diabetic complications, which largely influence on prognosis of diabetes in these patients. The etiopathogenesis of this complication is multifactorial one and it has still not been completely elucidated, but includes morphological, pathological-anatomic and biochemical metabolic disorders. It is considered that disorders of endothelial modular function might be critical and initial factor in the development of diabetic vascular complications. Based on pharmacodynamic effects of prostacyclin (PGI2) and its analogues, it could be said that they may be useful in the treatment of diabetic nephropathy. The main aim of this study was to assess the effects of prostacyclin (PGI2) in the treatment of diabetic nephropathy that was experimentally induced with streptozocin. Diabetes was induced in normotensive Wistar strain rats by single i.p. administration of streptozocin (STZ) and as a complication of diabetes and distinct signs and symptoms of diabetic nephropathy (proteinuria, increased serum level of urea and creatinine, polyuria, increased NAG activity in urine). Treatment with prostacyclin (p.o.) at dose of 0.1 mg/kg/b.w./daily during 4 weeks caused a significant reduction of the signs and symptoms of kidney failure as compared to control group of animals that were not given prostacyclin. The results obtained have shown that prostacyclin may have an important role in treatment of diabetic nephropathy, experimentally induced with streptozocin.

Role of endoethelin-1 in development of neprhopathy induced with streptozocin

The main aim of our study was to detect changes in plasma level of endoethelin-1 after experimentally induced diabetes and diabetic nephropathy with streptozocin in rats. The effects of ACE inhibitors are well known and thus, we wanted to analyze the influence of enalapril (ACE inhibitor) on plasma concentrations of endoethelin-1 as well as its effects in the treatment of diabetic nephropathy. Single i.p. administration of streptozocin (STZ) caused a significant increase of endoethelin-1 plasma concentrations associated with distinct signs and symptoms of diabetic nephropathy (microalbuminuria, increased urine N-acetyl-D-glucosamidase, increased serum concentrations of urea and creatinine, polyuria). Four-week treatment with endoethelin-1 resulted in significant reduction of endoethelin-1 plasma concentrations and improved sings and symptoms of diabetic nephropathy. The results obtained have confirmed that endoethelin-1 may play an important role in development and progression of diabetic nephropathy and ACE inhibitors, that is enalapril, may alleviate and delay the progression of diabetic nephropathy