Streptozotocin-induced Diabetic Nephropathy In Rats Research Articles

Hibiscus sabdariffa extract augments the renoprotective effect of lisinopril against streptozotocin-induced diabetic nephropathy in rats

Hibiscus sabdariffa extract augments the renoprotective effect of lisinopril against streptozotocin-induced diabetic nephropathy in rats

Zinc Chloride Protects against Streptozotocin-Induced Diabetic Nephropathy in Rats

Diabetes mellitus (DM) is a health problem affecting millions of individuals worldwide. Diabetic nephropathy (DN), as a significant complication of DM, has become the most common cause of endstage renal failure. Oxidative stress constitutes the key and common events in the pathogenesis of DN and antioxidants may play a beneficial role in its prevention. This study was conducted to investigate the effect of Zinc Chloride on streptozotocin-induced diabetic nephropathy in rats compared to Gliclazide, a reference antidiabetic agent. Results showed that Zinc Chloride was able to control STZ-induced DN in rats as it normalized the elevated blood pressure, the increased insulin release, and the decreased blood glucose level. Zinc Chloride also improved kidney function as determined by the restoration of blood urea and creatinine level. Finally, Zinc Chloride was able to boost the antioxidant defenses of the kidney by increasing the reduced glutathione content and decreasing lipid peroxides content in addition to significantly decreasing kidney nitric oxide content compared to diabetic control rats. These results suggest that exposure to Zinc Chloride can protect from diabetic nephropathy and can be used as an adjuvant approach to treatment and prevention of renal damage.

Effects of rosuvastatin on the progression of diabetic nephropathy in streptozotocin-induced diabetic rats

Effects of rosuvastatin on the progression of diabetic nephropathy in streptozotocin-induced diabetic rats

Therapeutic insight into molsidomine, a nitric oxide donor in streptozotocin-induced diabetic nephropathy in rats.

Background:Diabetes-induced oxidative stress and hypertension play a major role in the development of nephropathy. Hence, the present study was undertaken to evaluate the protective effects of molsidomine, a nitric oxide donor in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats.Materials and Methods:Type 1 diabetes was induced through a single dose of STZ (52 mg/kg, i.p.) in male Wistar rats and then treated with molsidomine (5 and 10 mg/kg; p.o.) for 8 weeks. Physical parameters, vital and renal function test including blood glucose, albuminuria, blood urine nitrogen, serum creatinine, and kidney index were determined. Oxidative stress and lipid peroxidation were assessed in the kidney homogenate by means of antioxidant enzymes and malondialdehyde levels.Results:DN rats exhibited a significant renal dysfunction with a reduction in body weight, excessive oxidative stress, and pathological changes. Molsidomine treatment significantly improved vital sign, renal functions, and oxidative stress in DN rats in a dose-dependent manner. The protective effect of molsidomine was also substantiated by pathological changes in the architect of the kidney.Conclusion:Molsidomine shows a significant beneficial effect in Type 1 DN in rats.

The effects of ozone therapy on caspase pathways, TNF-α, and HIF-1α in diabetic nephropathy.

Accelerated apoptosis plays a vital role in the development of diabetic vascular complications. Ozone may attenuate diabetic nephropathy by means of decreased apoptosis-related genes. The aim of our study was to investigate the effect of ozone therapy on streptozotocin-induced diabetic nephropathy in rats. Also the histopathological changes in diabetic kidney tissue with ozone treatment were evaluated. The rats were randomly divided into six groups (n = 7): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). D, DI, and DOI groups were induced by a single intraperitoneal injection of streptozotocin. Ozone was given to the O, DO, and DOI groups. Group DI and DOI received subcutaneous (SC) insulin (3 IU). All animals received daily treatment for 6 weeks. Expressions of caspase-1-3-9, HIF-1α, and TNF-α genes were significantly higher in D group compared to C group (p < 0.05 for all). Ozone treatment resulted in significant decrease in the expressions of these genes in diabetic kidney tissue compared to both C and D group (p < 0.05 for all). Caspase-1-3-9, HIF-1α, and TNF-α gene expressions were found to be lower in DOI group compared to C group (p < 0.05 for all). Also adding ozone treatment to insulin therapy resulted in more significantly decrease in the expressions of these genes in diabetic tissue compared to only insulin-treated diabetic group (p < 0.05 for all). Regarding histological changes, ozone treatment resulted in decrease in the renal corpuscular inflammation and normal kidney morphology was observed. Both insulin and ozone therapies apparently improved kidney histological findings with less degenerated tubules and less inflammation of renal corpuscle compared to D, DO, and DI groups. Ozone therapy decreases the expressions of apoptotic genes in diabetic kidney tissue and improves the histopathological changes.

Progesterone ameliorates diabetic nephropathy in streptozotocin-induced diabetic Rats.

BackgroundPrevious studies reported that 17β-estradiol may influence the progression of diabetic renal disease in females. The present study was intended to provide an insight into the specific effects of progesterone, the other female sex hormone, in the diabetic renal complications.MethodsAdult female wistar rats were divided into four groups (n = 6/group): intact control (non-diabetic, ND), intact diabetic (D), ovariectomized diabetic (D-OVX) and ovariectomized diabetic which were treated with progesterone (D-OVX + P; 10 mg/kg, s.c, every second day) for 10 weeks. Diabetes was induced by a single dose injection of 55 mg/kg streptozotocin. Expressions of transforming growth factor-β (TGF-β), fibronectin, vascular endothelial growth factor-A (VEGF-A), angiotensin II type 1 receptor (ATR1) and podocyte markers (nephrin and podocin) were assessed by immunohistochemistry and real-time PCR.ResultsThe treatment of D-OVX rats with progesterone attenuated diabetic-associated increases in the urinary albumin to creatinine ratio, glomerulosclerosi and the expression of profibrotic and angiogenic factors (TGF-β, Fibronectin and VEGF-A). Furthermore, progesterone supplementation prevented diabetes-induced downregulation of nephrin and podocin while the overexpression of ATR1 in the diabetic rats was inhibited by the progesterone supplementation.ConclusionThese results provided evidence, for the first time, that the replacement of progesterone can ameliorate the renal damage in the experimental models of diabetic nephropathy through improving the renal function; the inhibition of renal fibrosis and abnormal angiogenesis; along with the amelioration of podocyte injury. Additionally, the blocking of renin-angiotensin system through the down-regulation of ATR1 expression may also account for the reno-protective effect of progesterone.Electronic supplementary materialThe online version of this article (doi:10.1186/s13098-015-0097-1) contains supplementary material, which is available to authorized users.

Xiaokeping mixture inhibits diabetic nephropathy in streptozotocin-induced rats through blocking TGF-β1/Smad7 signaling.

BackgroundDiabetic nephropathy (DN) is a major cause of chronic kidney failure and characterized by excessive deposition of extracellular matrix. Evidence have shown that transforming growth factor-β1 (TGF-β1) is a key mediator in the development of DN. However, treatment of DN by blocking the TGF-β1/Smad7 pathway remains limited. Xiaokeping mixture (XKP), a traditional Chinese herbal compound, has been used for treatment in patients with DN for many years.MethodsIn the present study, TGF-β1/Smad7 pathway analysis was used to evaluate the therapeutic effect of XKP on DN rats induced by streptozotocin and to address the underlying molecular mechanism. Male rats were divided into four groups: normal control, untreated control group (fed with high fat), irbesartan-treated DN, and XKP-treated DN, respectively. Levels of serum creatinine, blood urea nitrogen, urine protein of 24 hours, and triacylglycerol were detected. Pathological changes of renal tissues were observed by hematoxylin–eosin staining. Immunohistochemical and Western blot analysis were used to detect the expressions of TGF-β1 and Smad7.ResultsThe results demonstrated that XKP can effectively reduce the levels of glucose, serum creatinine, blood urea nitrogen, urine protein of 24 hours, and triacylglycerol. Further studies indicated that inhibition of DN in XKP-treated DN rats was associated with inhibition of TGF-β1/Smad7 signaling as demonstrated by downregulation of TGF-β1 but upregulation of Smad7.ConclusionThe data obtained from the present study indicate that XKP may be a therapeutic agent for DN.

Pterostilbene alleviates diabetic nephropathy in experimental diabetic rats; inhibition of aldose reductase and advanced glycation end products formation

Various mechanisms including polyol pathway along with a complex integrating paradigm with oxidative stress and advanced glycation end products (AGE) formation have been implicated in the pathogenesis of diabetic nephropathy. The present study was aimed at investigating a well known antioxidant, pterostilbene for its therapeutic role in streptozotocin-induced diabetic nephropathy in rats. The effect of pterostilbene was investigated by assessing the key markers of kidney function along with the morphological changes in the kidney. Further, the effect of pterostilbene on the formation of AGEs, aldose reductase (AR) inhibition and lipid peroxidation was compared with that of a standard AR inhibitor, fidarestat. The results revealed that pterostilbene significantly decreased the blood glucose levels, urinary protein excretion, serum creatinine and blood urea nitrogen in diabetic rats. Administration of pterostilbene to diabetic rats decreased kidney lipid peroxides and nitrate levels along with decrease in AGEs formation. In addition, pterostilbene was found to inhibit kidney AR activity with a decrease in serum TGF β levels. Thus, the results obtained in this study underline the potential of pterostilbene as a possible therapeutic agent against diabetic complications such as nephropathy.

Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats.

PurposeTo investigate the therapeutic effects and potential mechanisms of icariside II (ICA II) on reversing diabetic nephropathy in streptozotocin (STZ)-induced type I diabetic rats.MethodsNewborn male Sprague Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for tracking endogenous label retaining progenitor cells (LRCs). At age of 8 weeks, 48 rats were randomly divided into three groups: normal control group (n=16), diabetes mellitus group (DM; n=16), and diabetes mellitus plus ICA II therapy group (DM+ICA II, n=16). Eight weeks induced for diabetes with STZ, rats in DM group and DM+ICA II group were treated with vehicle or ICA II (5 mg/kg/day) for another 8 weeks, respectively. Then, blood creatinine, 24-hour urine protein, blood urea nitrogen, and glycosylated hemoglobin were measured, as well as the expression of von Willebrand factor, malondialdehyde, transforming growth factor-β/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-β/Smad/CTGF) signaling, marker of proliferation Ki-67, and EdU+ LRCs in renal tissues.ResultsIncreased levels of creatinine, 24-hour urine protein, and blood urea nitrogen and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly downregulate the levels of malondialdehyde and TGF-β/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney.ConclusionICA II treatment could ameliorate diabetic nephropathy in STZ-induced diabetic rats by increasing endothelial cell contents, downregulating TGF-β/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation both in kidney cortex and medulla. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU+ progenitor cells into the kidney tissue.

Enhanced Homing Ability and Retention of Bone Marrow Stromal Cells to Diabetic Nephropathy by Microbubble-Mediated Diagnostic Ultrasound Irradiation

Bone marrow stromal cell (BMSC) transplantation can successfully treat diabetic nephropathy (DN), but the lack of a specific homing place for intravenously injected cells limits the effective implementation of stem cell therapies. The migration and survival of transplanted BMSCs are determined by inflammatory reactions in the local kidney micro-environment. We tested the hypothesis that microbubble-mediated diagnostic ultrasound irradiation could provide a suitable micro-environment for BMSC delivery and retention in DN therapy. In this study, red fluorescent protein–labeled BMSCs were administered combined with microbubbles to streptozotocin-induced DN rats 4 wk after diabetes onset. We observed enhanced BMSC homing and retention in microbubble-mediated diagnostic ultrasound-irradiated kidneys compared with the contralateral kidneys on days 1 and 3 post-treatment. The results from immunohistochemical analysis, Western blot and enzyme-linked immunosorbent assay indicated that the local and transient expression of various chemo-attractants (i.e., cytokines, integrins and trophic factors) found to promote BMSC homing was much higher than observed in non-treated kidneys. The local capillary endothelium rupture observed by transmission electron microscopy may account for local micro-environment changes. Histopathologic analysis revealed no signs of kidney damage. These results confirmed that renal micro-environment changes caused by appropriate microbubble-mediated diagnostic ultrasound irradiation may promote BMSC homing ability to the diabetic kidney without renal toxicity and cell damage. This non-invasive and effective technique may be a promising method for BMSC transplantation therapy.

AB176. Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats

ObjectiveTo investigate the therapeutic effects and potential mechanisms of icariside II (ICA II) on improving diabetic nephropathy (DN) in streptozotocin (STZ) induced type I diabetic rats.MethodsNewborn male Sprague-Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for tracking endogenous label retaining progenitor cells (LRCs). At age of 8 weeks, 16 rats were chosen as normal control (NC) and 32 rats were induced for diabetes with STZ, 8 weeks later, diabetic rats were equally randomized into diabetic group (DM) and ICA II therapy group (DM + ICA II) that were treated with vehicle or ICA II (5 mg/kg/day) for 8 weeks, respectively. Then blood creatinine (Cr), 24-h urine protein, blood urea nitrogen (BUN), and HbA1c were measured, as well as the expression of von Willebrand Factor (vWF), MDA, TGF-β/Smad/CTGF signaling, Ki67, and EdU + LRCs in renal tissues.ResultsIncreased levels of Cr, 24-h urine protein, and BUN, and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly down-regulate the levels of MDA and TGF-β/Smad/CTGF signaling and increase the expression of vWF, Ki67, and EdU + LRCs in the kidney.ConclusionsICA II treatment could ameliorate DN in STZ-induced diabetic rats by increasing endothelial cell contents, down-regulating TGF-β/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU + progenitor cells into the kidney tissue.

Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats

ObjectivesVitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. MethodsMale Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. ResultsTreatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca2+ and Na+/K+-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. ConclusionVitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy.

Nephro-Protective Effect of Cortex Lycii Radicis Extracts in Streptozotocin- Induced Diabetic Rats

Background: To evaluate the effects of aqueous Cortex Lycii Radicis (CLR) extracts on diabetic nephrology in a streptozotocin-induced diabetic nephropathy rat model, and to explore the underlying mechanisms of CLR action. Methods: We induced diabetes mellitus via a single intravenous streptozotocin injection (30 mg/kg) and subsequent high-fat diet for 3 weeks in male Sprague Dawley rats. Rats that developed diabetes mellitus were randomized to receive normal saline (vehicle, n=10), low-dose CLR (15 g/kg/day, n=10), or high-dose CLR (30 g/kg/day, n=10), and rosiglitazone (2 mg/kg/day, n=10) daily for 8 weeks. In addition, 10 normal rats served as controls. Kidneys were removed to evaluate histological renal glomeruli alterations using periodic acid–Schiff (PAS) staining. Results: Fructosamine, and blood urea nitrogen concentrations, as well as the urinary albumin excretion rate (AER), were increased in vehicle-treated diabetic rats compared to control rats (P<0.05). These parameters decreased upon CLR treatment, particularly at low-dosage CLR (P<0.05). Morphologic observations showed that high-dosage CLR markedly attenuated diabetes-associated renal injury. The renal protective effects of CLR may be mediated by downregulation of cytokine expression, including TGF-α and interleukin 6. Conclusion: CLR accelerates functional and histological kidney recovery, thereby delaying diabetic nephropathy progression. Therefore, it may be a novel therapeutic approach for the treatment of diabetic nephrology. Keywords: Chinese medicine, Cortex Lycii Radicis, diabetic nephropathy, traditional.

Role of Targeting Asymmetric Dimethylarginine in Streptozotocin-Induced Diabetic Nephropathy in Rats: Effects of Taurine and Rosiglitazone

Role of Targeting Asymmetric Dimethylarginine in Streptozotocin-Induced Diabetic Nephropathy in Rats: Effects of Taurine and Rosiglitazone

The ameliorative effect of Heme Oxygenase System on early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

The ameliorative effect of Heme Oxygenase System on early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats

Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved.Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ) (55mg/kg). The diabetic rats were orally treated with spironolactone (50mg/kg/day) and/or candesartan (1mg/kg/day) for 8 weeks.Administration of STZ caused a marked elevation in the serum level of creatinine, urea and urinary albumin–creatinine ratio (ACR). This was associated with upregulated renal protein levels of nuclear factor-kappa B (NF-κB), transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) alongside increasing the renal superoxide anion (O2−) production, malondialdehyde (MDA) level and the systolic blood pressure. There was a marked decrease in nitric oxide (NO) bioavailability and antioxidant enzyme capacity. The combined therapy of spironolactone and candesartan significantly normalized the oxidative stress and fibrotic/inflammatory alterations. Additionally, the elevated blood pressure was attenuated by administration of candesartan alone or in combination. This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy.In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers.

Secoisolariciresinol diglucoside in high-fat diet and streptozotocin-induced diabetic nephropathy in rats: a possible renoprotective effect.

Due to substantial morbidity and high complication rate of diabetes mellitus, which is considered as the third killer in the world, a search for the effective blockade of the progression of diabetic nephropathy (DN) remains a therapeutic challenge. Alternative antidiabetic drugs from natural plants are highly demanded nowadays. The aim of this study was to investigate the renoprotective effect of secoisolariciresinol diglucoside (SDG) on DN induced in rats. Diabetes was induced in male Sprague-Dawley rats by a high-fat diet (HFD) and an intraperitoneal 35 mg/kg streptozotocin (STZ) injection. Rats were divided into four groups: normal control rats, diabetic control rats, diabetic rats treated with SDG at 10 mg/kg/day for 4 weeks, and diabetic rats treated with SDG at 20 mg/kg/day for 4 weeks. At the end of the treatment, blood and renal tissue samples were collected for biochemical examination. The results revealed that SDG treatment significantly increased insulin level and decreased blood glucose, fructosamine, creatinine, and blood urea nitrogen levels in diabetic rats. Also, SDG significantly increased renal reduced glutathione, superoxide dismutase and decreased malondialdehyde and nitric oxide levels. In addition, SDG downregulated the renal nuclear factor kappa-B (NF-κB), tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) and upregulated renal survivin and B-cell lymphoma-2 (Bcl-2) expressions when compared with untreated diabetic control rats. This study demonstrated, for the first time, the renoprotective effects of SDG in HFD/STZ-induced DN in rats through correction of hyperglycemia; attenuation of oxidative/nitrosative stress markers; downregulation of renal expressions of inflammatory markers NF-κB, TNF-α, and iNOS; along with upregulation of renal expressions of antiapoptotic markers survivin and Bcl-2.

Vitamin D prevents podocyte injury via regulation of macrophage M1/M2 phenotype in diabetic nephropathy rats.

Increasing evidence suggests the heterogeneity of macrophage phenotype and function ultimately determines the outcome of diabetic nephropathy (DN). This study aimed to investigate the effects of vitamin D on macrophage M1/M2 phenotype and its role in preventing podocyte impairment in streptozotocin-induced DN rats. Calcitriol, a bioactive 1,25-dihydroxyvitamin D3, ameliorated proteinuria and renal damage as well as reversed the decline of both nephrin and podocin, crucial structural proteins in podocytes. DN rats showed increased infiltrating macrophages with M1 phenotype characterized by elevated expression of inducible nitric oxide synthase and TNF-α in glomeruli and interstitium, which were inhibited after calcitriol treatment. Interestingly, calcitriol promoted M2 macrophage activation with enhanced expression of CD163, arginase-1, and mannose receptor at week 18 but not at week 8 or 14. The ratio of CD163 to CD68, considered as the proportion of M2 macrophages, was about 2.9-fold higher at week 18 after calcitriol treatment. Furthermore, the protein expression of inducible nitric oxide synthase, a crucial marker of M1 macrophages, was negatively correlated with the expression of either nephrin or podocin, whereas CD163, indicating M2 macrophages, was positively correlated. In vitro, 1,25-dihydroxyvitamin D3 switched high-glucose-induced M1 macrophages toward an M2 phenotype in either U937-derived macrophages or RAW264.7 cells. Our results suggest that vitamin D not only reduces macrophage infiltration and inhibits M1 macrophage activation but also enhances M2 macrophage phenotype to protect against podocyte injury.

Effects of Tephrosia purpurea and Momordica dioica on streptozotocin-induced diabetic nephropathy in rats

Present study investigated the effects of Tephrosia purpurea (TP) and Momordica dioica (MD) in streptozotocin-induced diabetic nephropathy in wistar rats. Rats were divided into 12 groups (n=6). Diabetes was induced with a single dose of streptozotocin (55mg/kg i.p.). Day 4 of the study was considered first day of the study as administration of ethanolic extracts of TP leaves and MD fruits were started on 4th day. In protective regimen (initial 26days of experimental period), ethanolic extract was administered orally at 200 and 400mg/kg/day, whereas curative regimen began after 26days and continued up to 40days. Diabetic control group was considered as standard for comparison. Serum glucose, urea, creatinine and urine albumin levels were significantly lower in treated groups as compared to the diabetic control. Malondialdehyde was significantly (P<0.001) lowered in treated groups as compared to diabetic control group. Treated groups have shown significant increase (P<0.001) in reduced glutathione level which was reduced in diabetic control group. Change in body weight was found to be non-significant in treated groups. It was concluded that TP leaf and MD fruit extracts can provide a radical cure for drug-induced diabetic nephropathy by a reduction in renal damage.

Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats.

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia-reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents (p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (p < 0.01) and XO (p < 0.05) activities and elevated GSH (p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group (p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.