Renal Function In Diabetic Rats Research Articles

PURIFIED GAMBIR (UNCARIA GAMBIR (HUNTER) ROXB.) ATTENUATE RENAL FUNCTION IN ALLOXAN-INDUCED DIABETIC MALE RATS

Objective: Diabetes and its vascular complications could prevent by antioxidants. Purified gambir is the purified extract of Uncaria gambir (Hunter) Roxb, which contains more than 90% catechins and scientifically work as antioxidant. This study aimed to determine the effect of purified gambir on renal function in alloxan-induced diabetic Wistar Kyoto rats.
 Methods: Diabetic rats were induced by alloxan 125 mg/kgBW by intraperitoneal injection. Forty-five diabetic rats were divided into five groups, diabetic control group treated with vehicle, a positive control group treated with glibenclamide at dose 0.45 mg/kgBW, and treatment groups of purified gambir at doses of 2.50, 5, and 10 mg/kgBW for 14 d. Blood glucose, water intake, urine volume, creatinine clearance, renal ratio, and urine density were measured on day 3, 7, and 14. All data were analyzed by two-way ANOVA followed by Duncan Multiple Range Test.
 Results: Purified gambir significantly lower blood glucose (p<0.05) and had a significant effect (p<0.05) on renal function parameters in diabetic rats. Duration of treatment purified gambir in diabetic rats had a significant effect (p<0.05) on water intake, urine volume, creatinine clearance and renal ratio.
 Conclusion: This result show that purified gambir at dose 2.5 mg/kgBW increased the renal function of diabetic rats, in contrast, purified gambir at dose 5 and 10 mg/kgBW attenuate renal function of diabetic rats

Bacoside-A Improves Antioxidant Enzymes and Alleviates Oxidative Stress Coexist with Markers of Renal Function in a Rat Model of Type 2 Diabetes Mellitus.

Oxidative stress, imbalanced antioxidants, and dysregulated renal lipids are closely linked with diabetic nephropathy and eventual cause of end-stage renal failure. This study was performed to investigate the protective effect of bacoside-A on markers of lipid peroxidation, renal lipids, and markers of renal function in diabetic rats. Experimental diabetes was induced in Wistar rats by a single dose of streptozotocin [40 mg/kg body weight (BW)] via intraperitoneal injection. Oral administration of bacoside-A (10 mg/kg BW) and glibenclamide, a reference drug, continued for 45 days. Diabetic rats showed a significant increase in the levels of plasma glucose, renal lipids, markers of renal lipid peroxidation, and plasma biomarkers of renal function such as urea, uric acid, and creatinine. A significant decrease in the levels of plasma insulin, nonenzymatic antioxidants, and the activity of enzymatic antioxidants was seen compared with the normal controls. Bacoside-A (10 mg/kg BW) and glibenclamide (600 μg/kg BW) administered to diabetic rats resulted in a significant decrease in plasma glucose and renal lipids but a significant increase in the plasma insulin level. In addition, bacoside-A achieved a remarkable increase in the activity of enzymatic antioxidants and the levels of nonenzymatic antioxidants in the renal tissue of diabetic rats, along with significant decreases in the markers of lipid peroxidation and those of renal function, consequently substantiating the protecting effectiveness of bacoside-A in a diabetic state. These biochemical observations were supported by a histopathological study of the renal tissue. The present study suggested that bacoside-A, a triterpenoid, offers a higher renoprotective effect to counter abnormal parameters of renal function in diabetes-induced renal injury.

Nephroprotective Effects of Mycophenolate Mofetil and Glibenclamide on Streptozotocin-induced Diabetic Renal Injury in Rats: An Experimental Study.

Diabetic renal injury is a microvascular complication associated with inflammation and oxidative stress, culminating in renal dysfunction. Conventionally, it is treated with hypoglycemic agents to address metabolic perturbations. However, the way to mitigate immunological, inflammation, and oxidative stress have seldom been studied. Hence, in the present study, the nephroprotective role of immunosuppressive and anti-inflammatory drugs, mycophenolate mofetil (MMF) in combination with the oral hypoglycemic agent glibenclamide, on streptozotocin (STZ)- induced diabetic renal damage was studied. Bodyweight, fasting blood glucose, and glycosylated hemoglobin levels were altered in the diabetic rats. Furthermore, renal injury was indicated by abnormal levels of urinary protein and creatinine and serum markers of renal function in diabetic rats. Hyperglycemia-induced oxidative stress and inflammation were also observed in the diabetic rats. The combination of MMF and glibenclamide treatment significantly attenuated the abnormal effects of hyperglycemia, oxidative stress, and inflammation-induced renal injury in diabetic rats. Histopathological studies confirmed the nephroprotective role of MMF and glibenclamide by reversing renal injury in diabetic rats. The present study suggests that MMF and glibenclamide have a protective role in STZ-induced diabetic renal damage.

Shenkang protects renal function in diabetic rats by preserving nephrin expression

BackgroundShenkang injection has been used clinically to lower creatinine levels. This study explored the mechanism of Shenkang injection on protecting kidney function from hyperglycemia-mediated damage.MethodsThis study utilized a STreptoZotocin (STZ)-induced rat model of diabetes. In total, 60 rats were randomized into either the control group (n = 15) injected with vehicle or treatment group (n = 45) injected with STZ to induce hyperglycemia. Eight weeks after diabetes onset, diabetic rats were further randomized to receive different treatments for 4 consecutive weeks, including vehicle (diabetic nephropathy group, n = 15), Shenkang (n = 15), or Valsartan (n = 15). At 12 weeks, a series of urine and blood measures were examined and damage to the kidney tissue was examined using histology. Expression of nephrin and transforming growth factor-β1 (TGF-β1) were characterized using immunohistochemistry and Western blot.ResultsCompared to the control group, rats in the diabetic nephropathy group showed significant kidney damage demonstrated by high kidneyindex, high levels of urinary albumin, albumin/creatinine ratio (ACR), blood urea nitrogen as well as histological evidence. Shenkang injection significantly improved kidney function in the diabetic rats by decreasing kidney index, ACR, and serum creatinine. Shenkang treatment also mitigated kidney damage, improved nephrin expression, and decreased TGF-β1 expression in the kidneys.ConclusionsShenkang treatment protected renal function in diabetic rats by increasing nephrin expression, which protects diabetic rats from hyperglycemia-mediated kidney damage.

ASSESSMENT OF RENAL FUNCTION IN DIABETIC WISTAR RATS TREATED WITH ETHANOL EXTRACT OF Cucumis sativus FRUIT.

As a fast-growing metabolic disorder diabetes mellitus is one of the leading causes of death worldwide. Nephropathy (damage to kidney leading to renal failure) is a microvascular complication of the disease. The aim of the present study was to assess renal function in diabetic rats treated with ethanol extract of Cucumis sativus fruit. Male Wistar rats (n = 25, mean weight = 215 ± 15 g) were randomly assigned to five groups (5 rats per group): control, diabetic, metformin, 200 mg/kg body weight (bwt) extract and 300 mg/kg bwt extract groups. Diabetes mellitus was induced in the rats via intraperitoneal injection of streptozotocin (STZ) at a dose of 50 mg/kg bwt. The diabetic rats were then treated for 21 days with metformin (50 mg/kg bwt) or the extract at doses of 200 and 300 mg/kg bwt, respectively, leaving the diabetic group untreated. The results showed that induction of diabetes mellitus using STZ significantly increased plasma urease activity, and urea and chloride concentrations, but it reduced the weight of rat kidney and concentrations of sodium, potassium and bicarbonate ions significantly (p < 0.05). However, treatment of the diabetic rats with the extract markedly reduced plasma urease, and urea and chloride ion concentrations, while increasing kidney weight, organ/body weight ratio as well as concentrations of sodium, potassium and bicarbonate ions (p < 0.05). The effect of the extract on potassium and chloride ions was dose-dependent. These results indicate that ethanol extract from the medicinal plant C. sativus fruit can ameliorate kidney dysfunction caused by STZ-induced diabetes mellitus.

Efficacy of Danggui Buxue decoction on diabetic nephropathy-induced renal fibrosis in rats and possible mechanism.

To observe the efficacy of Danggui Buxue decoction (, DBD) on diabetic nephropathy-induced renal fibrosis in rats, and to study the possible mechanism. Sixty male Goto Kakizaki (GK) rats were randomly assigned to the model group, gliquidone group, astragaloside IV group, and high-, medium- and low-doses DBD groups. After 8 weeks, changes in body weight, blood glucose, serum creatinine, serum urea nitrogen, and total cholesterol were observed. Changes in transforming growth factor-β1 (TGF-β1), Smad3, and Smad5 pathways and the expression of the fibrosis-related proteins collagen IV (col IV), α-smooth muscle actin (α-SMA), and vimentin were assessed. The degree of renal fibrosis was observed by immunohistochemistry and Mason staining. The expression of interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) in the kidneys was assessed using enzyme linked immunosorbent assay. Our experiments showed that DBD effectively reduced blood glucose, blood urea nitrogen, and creatinine levels after 8 weeks of administration, improved renal function in diabetic rats, alleviated renal fibrosis, and reduced the renal tissue levels of IL-6, IL-10, TNF-α, and CRP. Furthermore, DBD decreased the expression of TGF-β1, Smad3, col IV, α-SMA, and vimentin in renal tissues and increased the expression of Smad5. DBD ameliorates diabetic renal interstitial fibrosis by modulating the TGF-β1/Smads pathway.

Melatonin prevents diabetes-induced nephropathy by modulating the AMPK/SIRT1 axis: Focus on autophagy and mitochondrial dysfunction.

Impaired nutrient sensing mechanisms such as AMPK/silent information regulator type 1 (SIRT1) axis and autophagy in renal cells upon chronic diabetic condition accelerate renal injury and upregulating these mechanisms has been reported to prevent renal damage. Melatonin, a neuroendocrine agent, also possess antioxidant and AMPK modulatory effect. In the current study, the protective effect of melatonin against diabetic renal injury was assessed in streptozotocin-induced diabetic nephropathy model and in in vitro model of high-glucose-induced tubular injury. Melatonin (3 and 10 mg/kg) was administered for 28 days after 4 weeks of diabetes induction in Sprague-Dawley rats. For in vitro model, the NRK-52E cells were co-incubated with high glucose and melatonin (25 and 50 μM). Melatonin supplementation abrogated the diabetes-induced renal injury and improved renal function in diabetic rats. Immunoblot analysis of renal tissue lysates revealed improved expression of AMPK, as well as upregulated the expression of nuclear factor erythroid 2-related factor 2, SIRT1, PGC-1α, TFAM and enhanced autophagy upon melatonin treatment in diabetic rats. Likewise, melatonin treatment in high glucose exposed NRK-52E cells improved expression of AMPK, enhanced mitochondrial biogenesis and positively modulated autophagy. However, these effects were repressed upon inhibition of AMPK activity in NRK-52E cells by treatment of Compound-C, suggesting that the protective effects of melatonin were mainly mediated through activation of AMPK. These results suggest that melatonin might mediate the renoprotective effect by upregulating the AMPK/SIRT1 axis, enhancing the autophagy and mitochondrial health in DIabetic Nephropathy.

Anti-angiogenesis and anti-inflammatory effects of Moringa oleifera leaf extract in the early stages of streptozotocin-induced diabetic nephropathy in rats

Objective: To investigate the effect of Moringa oleifera leaf extract on angiogenesis and inflammatory process in a rat model of streptozotocin-induced diabetic nephropathy. Methods: Four weeks after a single injection of 50 mg/kg streptozotocin, rats were treated with 100 or 200 mg/kg/day Moringa oleifera leaf extract, 1 mg/kg/day dapagliflozin, or a combination of Moringa oleifera leaf extract and dapagliflozin for further eight weeks. Renal function, kidney histology, and gene expression were evaluated at the end of the experiment. Results: Renal function of diabetic rats was significantly impaired as evidenced by increased blood urea nitrogen, albuminuria, 24-h proteinuria, and high creatinine clearance which indicated glomerular hyperfiltration. In addition, diabetic rats showed an increase in gene expressions of vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang2), the Ang2/Ang1 ratio, tumor necrosis factor-α, interleukin-1β and monocyte chemoattractant protein-1. Immunohistochemical staining demonstrated a significant increase in the density of glycoprotein CD34. Moringa oleifera leaf extract markedly improved all renal dysfunction markers and modulated the upregulated expression of angiogenic factors and inflammatory genes. Conclusions: Moringa oleifera leaf extract could suppress abnormal angiogenesis and inflammatory processes possibly by downregulating gene expression of angiogenesis factors and proinflammatory cytokines.

Short-Term Treatment of Metformin and Glipizide on Oxidative Stress, Lipid Profile and Renal Function in a Rat Model with Diabetes Mellitus

Background: Oxidative stress, lipid profile and renal functions are well-known conventional risk factors for diabetes mellitus (DM). Metformin and gliclazide are popularly used monotherapy drugs for the treatment of DM. Aims: This study aims to assess the short-term treatment of single and dual therapy of glipizide/metformin on oxidative stress, glycemic control, serum lipid profiles and renal function in diabetic rats. Methods: DM was induced in rats with streptozotocin (STZ), then five different treatments were applied, including group I (untreated healthy control), group II (diabetic and untreated), group III (diabetic and treated with metformin), group IVI (diabetic and treated with glipizide) and group V (diabetic and treated with a combination of metformin and glipizide. Lipid peroxidation (LPO), nitric oxide (NO), total antioxidant capacity (TAC), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and urea were measured. Results: Compared to the untreated DM group, FBG and HbA1c were significantly reduced in the DM groups (p < 0.01) treated with metformin (159.7 mg/dL & 6.7%), glipizide (184.3 mg/dL & 7.3%) and dual therapy (118 mg/dL & 5.2%), respectively. Treatment with dual therapy and metformin significantly decreased LPO and NO levels but increased TAC in diabetic rats more than glipizide compared to untreated diabetic rats. Furthermore, metformin (19.8 mg/dL, p < 0.001), glipizide (22.7 mg/dL, p < 0.001), and dual therapy (25.7 mg/dL, p < 0.001) significantly decreased urea levels in the treated rats compared to untreated DM rats (32.2 mg/dL). Both drugs and their combination exhibited a substantial effect on total cholesterol, HDL, LDL and atherogenic index. Conclusions: These results suggest that the therapeutic benefits of metformin and glipizide are complementary. Metformin exhibited superior performance in improving glycemic control and decreasing oxidative stress, while glipizide was more effective against dyslipidemia. These findings could be helpful for the treatment of future vascular patients, antilipidemic medicines and antioxidant therapy to improve the quality of life.

Anti-hyperglycaemic effects of dioxidovanadium complex cis-[VO2(obz)py] avert kidney dysfunction in streptozotocin-induced diabetic male Sprague-Dawley rats.

Despite the success of antidiabetic drugs in alleviation of hyperglycaemia, diabetic complications, including renal dysfunction, continue to be a burden. This raises the need to seek alternative therapies that will alleviate these complications. Accordingly, the aim of this study was to investigate the effects of dioxidovanadium(V) complex cis-[VO2(obz)py] on renal function in diabetic rats. Streptozotocin-induced diabetic rats were treated with cis-[VO2(obz)py] (40 mg·kg-1) twice every third day for five weeks. Diabetic untreated and insulin-treated rats served as the diabetic control and positive control, respectively. Blood glucose concentrations, water intake, urinary output, and mean arterial pressure (MAP) were monitored weekly for five weeks. Rats were then euthanized, and blood and kidney tissues were collected for biochemical analysis. Significant decreases in blood glucose concentrations, MAP, glomerular filtration rate (GFR), and SGLT2 expression, as well as plasma angiotensin and aldosterone concentrations, were observed in the treated groups compared with the diabetic control. The complex also increased urinary glucose concentrations, antioxidant enzymes GPx and SOD concentrations, and decreased MDA concentrations and kidney injury molecule (KIM-1) concentrations. These findings suggest that the anti-hyperglycaemic effects of this vanadium complex may ameliorate kidney dysfunction in diabetes.

Intervention of phlegm and blood stasis inhibits TGF-β1/Smad3 signaling pathway in the kidney of diabetic rats

To observe the effect of traditional Chinese medicine for intervention of phlegm and blood stasis in regulating TGF-β1/Smad3 signaling and relieving nephropathy in diabetic rats. SD rats were divided into blank group (NC), diabetic model group (MC group), intervention of phlegm and blood stasis (RPDBS) group, phlegm-removing (RP) group and blood-removing (DBS) group. Diabetic models were established in all the rats except for those in the blank group. After 4 weeks of feeding, the rats in RPDBS group, RP group and DBS group were given corresponding drug intervention for 8 weeks. HE staining was used to observe the changes in renal histopathology. Western blotting and real-time fluorescence quantitative PCR were used to detect the expression levels of transforming growth factor-β1 (TGF-β1) and Smad3. The structure and arrangement of the glomeruli and renal tubules improved significantly in the treatment groups in comparison with those in the MC group. The expression levels of TGF-β1, Smad3 and p-Smad3 were significantly downregulated at both the protein and mRNA levels in the treatment groups (P < 0.05), and the down-regulation was more obvious in RPDBS group than in RP group and DBS group (P < 0.05). Intervention of phlegm and blood stasis may inhibit the activation of TGF-β1/Smad3 signaling pathway and delay diabetic nephropathy and fibrosis to protect the renal function in diabetic rats.

TRPC6 Inactivation Does Not Protect Against Diabetic Kidney Disease in Streptozotocin (STZ)‐treated Sprague‐Dawley Rats

Glomerular TRPC6 channels are up‐regulated in rodent models of diabetes mellitus, but the role of TRPC6 in driving progression of experimental diabetic nephropathy is controversial. We recently used CRISPR/Cas9 methods to generate Sprague‐Dawley rats with a deletion in exon 2 of the Trpc6 gene that renders the channels non‐functional [1]. In addition, we observed that animals lacking functional TRPC6 were protected in the chronic puromycin aminonucleoside (PAN) model of acquired FSGS [1]. In the present study, 300‐gram adult Trpc6del/del rats and their wild‐type Trpc6wt/wt littermates were examined in the STZ model of type‐1 diabetes using protocols approved by the University of Houston IACUC committee. In our experiments, diabetes was induced by a single intraperitoneal injection of STZ, while controls received vehicle. Animals were not treated with insulin. STZ‐treated rats with severe hyperglycemia (>450 mg/dl) by 5 days after treatment were used for analysis and were monitored for the next 10 weeks. At 4 and 10 weeks after STZ treatment, compared to vehicle‐treated controls, STZ‐treated rats had severe hyperglycemia (745 ± 144 mg/dl, mean ± SD at 10 weeks). They also had elevated plasma triglycerides and total cholesterol, and failed to gain weight. STZ‐treated rats also exhibited markedly increased urine albumin excretion, increased blood urea nitrogen (BUN), and increased plasma creatinine and decreased creatinine clearance, indicating marked declines in renal function in diabetic rats. Two‐way ANOVA analyses of these datasets revealed no differences between Trpc6wt/wt and Trpc6del/del rats in any of these parameters. There was no time in the course of the experiment where we obtained functional data suggesting a protective effect of TRPC6 inactivation on blood glucose, or kidney function in STZ diabetes. Histological analysis carried out 10 weeks after STZ treatment revealed marked glomerular and tubulointerstitial disease in STZ‐treated rats. Mesangial expansion was the prominent feature in glomeruli of STZ‐treated animals, and glomeruli were less disrupted than we previously observed in the chronic PAN model [1]. Blind semi‐quantitative analysis of glomerular histology revealed a significant effect of STZ but no protective effect of TRPC6 inactivation on glomerular pathology. In summary, TRPC6 inactivation does not prevent declines in renal function and appears to have no protective effect in the STZ model of type‐1 diabetes in Sprague‐Dawley rats. This is in marked contrast to our previous work in chronic PAN nephrosis, where TRPC6 inactivation preserves renal function and histology.Support or Funding InformationSupported by NIH grant R01‐DK104708.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

MicroRNA-503 contributes to podocyte injury via targeting E2F3 in diabetic nephropathy.

Diabetic nephropathy (DN) is serious diabetic complication with capillary injury. Podocyte injury exerts a crucial effect on DN pathogenesis. MicroRNA-503 (miR-503) has been reported in various diseases including DN. Here, we investigated the detailed mechanism of miR-503 in the podocyte injury of DN. The functional role of miR-503 was investigated in cultured podocytes and diabetic rats. Podocyte injury was evaluated by migration and apoptosis experiments in podocytes and we observed that high glucose elevated miR-503 in a time and dose-dependent manner. Meanwhile, E2F transcription factor 3 (E2F3), as a crucial regulator in multiple diseases, was predicted as a potential target of miR-503 here. It was shown that E2F3 was greatly decreased in podocytes incubated with high glucose and miR-503 modulated its expression negatively. In addition, downregulation of E2F3 contributed to podocyte injury, which was reversed by miR-503 inhibitors in vitro. Furthermore, we proved that increase of miR-503 resulted in an unfavorable renal function in diabetic rats via targeting E2F3. These revealed for the first time that the overexpression of miR-503 promoted podocyte injury via targeting E2F3 in diabetic nephropathy and miR-503/E2F3 axis might represent a pathological mechanism of diabetic nephropathy progression.

Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model.

Ameliorated renal function has been reported after bariatric surgery, but the mechanisms underlying this phenomenon are not well-studied. To investigate whether the long non-coding RNA (lncRNA) MALAT1 mediates the amelioration of diabetic nephropathy after duodenal-jejunal bypass (DJB) surgery, rats were assigned randomly into four groups: diabetic (DM) group, DM with DJB surgery group, DM with sham surgery group, and healthy control group. Food intake, body weight, oral glucose tolerance test (OGTT), urine albumin excretion rate (UAER), and glomerular filtration rate (GFR) were measured and histological examination of renal sections was performed. For in vitro study, HK-2 cells were cultured under various glucose concentrations following MALAT1 siRNA transfection. Expression levels of MALAT1, SAA3, IL-6, and TNF-α in rat renal tissues or HK-2 cell lines were evaluated by qRT-PCR and/or ELISA. Results showed DJB surgery improved the renal function of diabetic rats, as indicated by ameliorated UAER and GFR and attenuated glomerular hypertrophy. Expression of MALAT1 and its downstream target SAA3 was significantly downregulated in renal tissues after DJB, which in turn decreased the expression of the pro-inflammatory cytokines IL-6 and TNF-α. Knockdown of MALAT1 in HK-2 cell lines further confirmed that expression levels of SAA3, IL-6, and TNF-α were regulated by MALAT1 under both low- and high-glucose conditions. Our findings suggest that MALAT1 is implicated in the improvement of renal function after DJB through regulation of its downstream targets SAA3, IL-6, and TNF-α.

Effects of a novel curcumin derivative on the functions of kidney in streptozotocin-induced type 2 diabetic rats

ObjectiveB6, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aimed to explore the efficacy of B6 on diabetic nephropathy and the related mechanisms.Materials and methodsThe effects of B6 were studied on fast-blood glucose, serum creatinine, urea nitrogen, urine albumen/24 h, pathological changes of main organs, the levels of ACE2 and ACE2 mRNA in the rat model of diabetes induced by streptozotocin.ResultsThe results showed that B6 treatment could reduce serum creatinine, urea nitrogen, urine albumen/24 h, decrease the level of AngII, improve the renal pathological changes in diabetic rats and increase the levels of ACE2 and ACE2 mRNA.ConclusionThese results suggested B6 could protect the renal function of diabetic rats. This study provided scientific basis for the further researches and clinical applications of B6.

Effect of human umbilical cord blood-derived mononuclear cells on diabetic nephropathy in rats

Diabetic nephropathy (DN) is damage to the kidney which can lead to chronic renal failure, eventually requiring dialysis. Diabetes mellitus is the most common cause of adult kidney failure worldwide in the developed world. The current work was designed to elucidate the effect of mononuclear cells (MNCs) injection on reverse DN in rats exposed to streptozotocin (STZ) injection compared to metformin as a known hypoglycemic drug, 40 Male rats were divided equally into 4 groups; normal control group, diabetic control group, MNCs group were diabetic rats treated with MNCs (30×106 MNCs/rat once iv dose) in the tail vein of the rat, and metformin group were diabetic rats treated with metformin (100mg/kg orally daily dose) for four weeks. The results indicated an improvement effect of MNCs and metformin on STZ-induced DN in rats, which was evidenced by significant decrease in urinary albumin/creatinine ratio, N-acetyl-β-d-glucosaminidase (NAG), urinary kidney injury molecule-1 (KIM-1), serum urea, serum creatinine and fasting blood glucose and significant increase in C- peptide level, compared to diabetic control group. Additionally MNCs treated group exhibited pronounced effects in all previous parameters compared to metformin treated group. It is proved that MNCs treatment was superior to metformin in controlling hyperglycemia, and improving renal function in diabetic rats.

Effect of turnip leaf and root extracts on renal function in diabetic rats

Today, global interest in the use of herbal medicine is increasing and evaluation of their efficacy have become more important .There are several evidence that suggest some herbal extracts have beneficial effects on diabetic nephropathy. The present study has been designed to examine protective role of edible parts of turnip (leave and root) on alloxan-induced diabetic rats. Diabetic rats were intragastrically treated either with aqueous extract of turnip leave or root (AETL or AETR) at concentrations of 200, 400 mg/kg/d for consecutives 8 weeks. The effects of AETL and AETR on fasting blood glucose (FBG) and kidney functional markers including: urine volume, 24-hour urine total protein (UTP), blood urea nitrogen (BUN), plasma creatinine (Cr) and quantitative morphometric analysis of glomeruli including; mesangial matrix expansion (MME), urinary space, tuft-to capsule adhesion, Bowman’s capsule (BC) thickening, glomerulosclerosis, capillary dilatation, and hyalinosis were monitored by routine measurements, biochemically and pathologically. Our results showed that AETL significantly decreased FBG levels, urine volume, UTP, BUN and plasma Cr in diabetic rats. Moreover, AETL with a dose dependent manner remarkably decrease glomerular lesions such as MME, tuft-to-capsule adhesion and BC thickening. However, treatment of AETR had undistinguishable effects on these parameters in diabetic rats. In conclusion, the biochemical and pathological assessed indicators showed varying degrees of improvement in AETL treated diabetic nephropathy rats. The results obtained in this work indicate that turnip leaf may be considered as an easily accessible dietary source for diabetic nephropathy patients.

Renal functional responses in diabetic nephropathy following chronic bilateral renal denervation.

Renal innervation operates in conjunction with the intrarenal renin-angiotensin system (RAS) to control tubular reabsorption of sodium and water. This relationship remains unexplored in diabetic nephropathy. This study investigates the effects of acute RAS inhibition and chronic renal denervation on renal function in diabetic rats. Diabetes was induced in mRen-2 rats prior to conducting chronic bilateral denervation in diabetic and normoglycaemic animals. At 12-weeks post-diabetic induction, renal haemodynamics and tubular handling of sodium and water were measured before and after acute captopril infusion. Neither GFR nor renal blood flow were affected by diabetes or chronic renal denervation alone. While captopril produced natriuretic and diuretic responses in chronically-denervated diabetic animals, shown by increases (P<0.05) of 38±14% in absolute (UNaV), and 71±20% in fractional sodium excretion (FENa), and 68±17% in urine volume (UV); in the innervated-diabetic group captopril produced anti-natriuretic effects (UNaV and FENa reduced by 41±10% and 29±13%, respectively; all P<0.05). This difference was not observed however in normoglycaemic groups where RAS inhibition produced anti-natriuretic (normoglycaemic denervated vs. innervated: 56±14% vs. 49±14% UNaV; 45±13% vs. 37±14% FENa) and anti-diuretic (normoglycaemic-denervated vs. innervated: 34±8% vs. 38±10% UV) effects in both denervated and innervated animals. These data indicate that renal neuronal control is altered in chronic hyperglycaemia. The role of the RAS in sodium conservation in the diabetic kidney, appears to be more significant in the absence of renal innervation, suggesting that the interaction between the RAS and renal sympathetic nervous system is responsible for changes in renal function in diabetic nephropathy.

Geniposide reduces development of streptozotocin-induced diabetic nephropathy via regulating nuclear factor-kappa B signaling pathways.

Renal pathology was a commonly seen complication in patients with diabetes. Geniposide (GPO) was previously demonstrated to modulate glucose metabolism in diabetes. This study was to investigate effects of GPO in streptozotocin-induced diabetic rats and its underlying mechanism. Renal function in diabetic rats was evaluated by levels of serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin. Renal inflammation was appraised by inflammatory cells infiltration and pro-inflammatory cytokines production. Renal monocytes, T lymphocytes infiltration, and intercellular adhesion molecule-1 (ICAM-1) expression were quantitated by immunohistochemistry. Moreover, renal nuclear factor-kappa B (NF-κB) was assayed by Western blotting. Diabetic rats showed renal dysfunction as evidenced by increased levels of Scr, BUN, urinary albumin, and elevator renal index. Histological examination revealed significant glomerular basement membrane (GBM) thickening. However, GPO notably improved renal function and diabetes-induced GBM changes. Additionally, diabetic rats showed noteworthy renal inflammation,as reflected by enhancement of monocytes and T lymphocytes infiltration, increased expression of ICAM-1, tumor necrosis factor-α, interleukin-1 (IL-1), and IL-6. Interestingly, the level of monocytes infiltration positively correlated with the severity of GBM. Further study indicated diabetic rats displayed increased activation of NF-κB, indicated by increased expression of NF-κB p65, IKKα, and p-IκBα in renal tissue. However, all the changes in renal inflammation and NF-κB pathway were obviously reversed in GPO-treated diabetic rats. Our works indicate GPO ameliorates structural and functional abnormalities of kidney in diabetic rats, which is associated with its suppression of NF-κB-mediated inflammatory response.

Comparison of the effects of levocetirizine and losartan on diabetic nephropathy and vascular dysfunction in streptozotocin-induced diabetic rats

This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress, nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated.Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to body weight ratio, serum albumin, urinary proteins and creatinine clearance). Moreover, levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by losartan. Moreover, levocetirizine, similar to losartan, reduced the enhanced responsiveness of diabetic aorta to phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of levocetirizine on diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular hypertrophy by levocetirizine than by losartan. In conclusion, levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than, losartan in streptozotocin-diabetic rats.