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  1. Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

    SciTech Connect

    Amirshahrokhi, K.; Dehpour, A.R.; Hadjati, J.; Sotoudeh, M.; Ghazi-Khansari, M.

    2008-10-01

    Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of {beta} cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a {mu}-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1{beta}, tumor necrosis factor-{alpha} and interferon-{gamma}] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of {beta} cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of {beta} cells and insulitis in the MLDS model of type 1 diabetes.

  2. Taenia crassiceps infection attenuates multiple low-dose streptozotocin-induced diabetes.

    PubMed

    Espinoza-Jiménez, Arlett; Rivera-Montoya, Irma; Cárdenas-Arreola, Roberto; Morán, Liborio; Terrazas, Luis I

    2010-01-01

    Taenia crassiceps, like other helminths, can exert regulatory effects on the immune system of its host. This study investigates the effect of chronic T. crassiceps infection on the outcome of Multiple Low Dose Streptozotocin-Induced Diabetes (MLDS). Healthy or previously T. crassiceps-infected mice received MLDS and type 1 diabetes (T1D) symptoms were evaluated for 6 weeks following the induction of MLDS. T. crassiceps-infected mice displayed lower blood glucose levels throughout the study. A significantly lower percentage of T. crassiceps-infected mice (40%) developed T1D compared to the uninfected group (100%). Insulitis was remarkably absent in T. crassiceps-infected mice, which had normal pancreatic insulin content, whereas uninfected mice showed a dramatic reduction in pancreatic insulin. Infected mice that received MLDS did not show an increase in their regulatory T cell population, however, they had a greater number of alternatively activated macrophages, higher levels of the cytokine IL-4, and lower levels of TNF-alpha. Therefore, infection with T. crassiceps causes an immunomodulation that modifies the incidence and development of MLDS-induced autoimmune diabetes.

  3. Down-regulation of multiple low dose streptozotocin-induced diabetes by mycophenolate mofetil

    PubMed Central

    MAKSIMOVIC-IVANIC, D; TRAJKOVIC, V; MILJKOVIC, DJ; STOJKOVIC, M MOSTARICA; STOSIC-GRUJICIC, S

    2002-01-01

    The new immunosuppressive agent mycophenolate mofetil (MMF) has been shown recently to exert a protective effects in certain animal models of autoimmunity, including diabetes in diabetes-prone bio-breeding (BB) rats. In the present study, the immunomodulatory potential of MMF was investigated in autoimmune diabetes induced by multiple low doses of streptozotocin (MLD-STZ) in genetically susceptible DA rats 20 mg STZ/kg body weight (b.w.) for 5 days] and CBA/H mice (40 mg STZ/kg b.w. for 5 days). In both species, short time treatment of animals with MMF (25 mg/kg) during the early development of the disease, as well as continuous MMF treatment, prevented the appearance of hyperglycaemia and inflammatory infiltrates in the pancreatic tissue. Moreover, clinical manifestations of diabetes were suppressed by application of the drug after the onset of clinical symptoms. Treatment with guanosine (1 mg/kg) in parallel with MMF completely reversed MMF activity in vivo, indicating that inhibition of inosine monophosphate dehydrogenase (IMPDH) was responsible for the observed suppressive effects. MMF-mediated protection from diabetes correlated with reduced ex vivo spontaneous spleen mononuclear cell (MNC) proliferation and defective adhesive cell interactions. MMF-treated animals also had lower local production of IFN-γ, as well as IL-12 and nitric oxide (NO) production by peripheral tissues (spleen and peritoneal cells), compared to that in control diabetic groups, while IL-10 level was elevated. Together, these data demonstrate that MMF interferes with autoimmune process in streptozotocin-induced diabetes at multiple levels, including lymphocyte proliferation and adhesion, as well as pro/anti-inflammatory cytokine balance. PMID:12165076

  4. Pterostilbene ameliorates intracerebroventricular streptozotocin induced memory decline in rats.

    PubMed

    Naik, Bhagyashree; Nirwane, Abhijit; Majumdar, Anuradha

    2017-02-01

    There is strong evidence that mitochondrial dysfunction mediated oxidative stress results in aging and energy metabolism deficits thus playing a prime role in pathogenesis of Alzheimer's disease, neuronal death and cognitive dysfunction. Evidences accrued in empirical studies suggest the antioxidant, anticancer and anti-inflammatory activities of the phytochemical pterostilbene (PTS). PTS also exhibits favourable pharmacokinetic attributes compared to other stilbenes. Hence, in the present study, we explored the neuroprotective role of PTS in ameliorating the intracerebroventricular administered streptozotocin (STZ) induced memory decline in rats. PTS at doses of 10, 30 and 50 mg/kg, was administered orally to STZ administered Sprague-Dawley (SD) rats. The learning and memory tests, Morris water maze test and novel object recognition test were performed which revealed improved cognition on PTS treatment. Further, there was an overall improvement in brain antioxidant parameters like elevated catalase and superoxide dismutase activities, GSH levels, lowered levels of nitrites, lipid peroxides and carbonylated proteins. There was improved cholinergic transmission as evident by decreased acetylcholinesterase activities. The action of ATPases (Na(+) K(+), Ca(2+) and Mg(2+)) indicating the maintenance of cell membrane potential was also augmented. mRNA expression of battery of genes involved in cellular mitochondrial biogenesis and inflammation showed variations which extrapolate to hike in mitochondrial biogenesis and abated inflammation. The histological findings corroborated the effective role of PTS in countering STZ induced structural aberrations in brain.

  5. Interleukin-17A deficiency ameliorates streptozotocin-induced diabetes.

    PubMed

    Tong, Zan; Liu, Weihuang; Yan, Huichao; Dong, Chen

    2015-10-01

    Interleukin-17 (IL-17) is a cytokine with critical functions in multiple autoimmune diseases. However, its roles in type I diabetes and the underlying mechanisms remain to be fully elucidated. In the current study, we investigated the impact of IL-17 deficiency on streptozotocin (STZ) -induced diabetes. Il-17(-/-) mice exhibited attenuated hyperglycaemia and insulitis after STZ treatment compared with control mice. The Il-17(-/-) mice had fewer CD8(+) cells infiltrating the pancreas than wild-type controls after STZ injection. Wild-type mice showed increased percentage and number of splenic CD8(+) cells and decreased Gr1(+)  CD11b(+) myeloid-derived suppressor cells (MDSC) after STZ treatment, but Il-17(-/-) mice maintained the percentages and numbers of splenic CD8(+) cells and MDSC, suggesting that IL-17 is implicated in STZ-induced cellular immune responses in the spleen. We further purified the MDSC from spleens of STZ-treated mice. Il-17(-/-) MDSC showed increased ability to suppress CD8(+) cell proliferation in vitro compared with wild-type MDSC. Transfer of MDSC to diabetic mice showed that MDSC from Il-17(-/-) mice could ameliorate hyperglycaemia. Moreover, recipients with MDSC from Il-17(-/-) mice had a decreased percentage of CD8(+) cell in the spleen compared with recipients with MDSC from wild-type mice. These data suggest that IL-17 is required in splenic MDSC function after STZ delivery. In summary, our study has revealed a pathogenic role of IL-17 in an STZ-induced diabetes model with important implications for our understanding of IL-17 function in autoimmune diseases.

  6. Carvedilol Ameliorates Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Morsy, Mohamed A.; Ibrahim, Salwa A.; Amin, Entesar F.; Kamel, Maha Y.; Abdelwahab, Soha A.; Hassan, Magdy K.

    2014-01-01

    Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10 mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor-α, and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury. PMID:24991534

  7. Total saponin of Dioscoreae hypoglaucae rhizoma ameliorates streptozotocin-induced diabetic nephropathy

    PubMed Central

    Guo, Changrun; Ding, Gang; Huang, Wenzhe; Wang, Zhenzhong; Meng, Zhaoqing; Xiao, Wei

    2016-01-01

    Background Diabetic nephropathy has become the most common cause of morbidity and mortality in diabetic patients. Therefore, there is an urgent need for more effective and safer drugs for use in this condition. Purpose The aims of this study were to investigate the ameliorative effects of total saponin of Dioscoreae hypoglaucae rhizoma (TSD) on diabetic nephropathy and to explore the potential underlying mechanism(s). Methods Rats with streptozotocin-induced diabetes were orally treated with TSD at 40, 80, and 160 mg/kg/d for 12 weeks. At the end of the treatment, blood, urine, and kidneys were collected for biochemical and histological examination. Results The results demonstrated that TSD significantly decreased the fasting blood glucose, glycosylated hemoglobin, urinary protein, serum creatinine, and blood urea nitrogen levels in diabetic rats. The results of histological examinations showed that TSD ameliorated glomerular and tubular pathological changes in diabetic rats. Furthermore, TSD significantly prevented oxidative stress and reduced the renal levels of advanced glycation end products, transforming growth factor-β1, connective tissue growth factor, and tumor necrosis factor-α. Conclusion This study demonstrated the renoprotective effects of TSD in experimental diabetic nephropathy via a number of different mechanisms. PMID:26966352

  8. Extract of Moringa oleifera leaves ameliorates streptozotocin-induced Diabetes mellitus in adult rats.

    PubMed

    Yassa, Hanan Dawood; Tohamy, Adel Fathy

    2014-06-01

    Medicinal plants attract growing interest in the therapeutic management of Diabetes mellitus. Moringa oleifera is a remarkably nutritious vegetable with several antioxidant properties. The present study assessed the possible antioxidant and antidiabetic effects of an aqueous extract of M. oleifera leaves in treating streptozotocin-induced diabetic albino rats. The antidiabetic effects of aqueous extract of M. oleifera leaves were assessed histomorphometrically, ultrastructurally and biochemically. Fasting plasma glucose (FPG) was monitored and morphometric measurements of β-cells of islets of Langerhans (modified Gomori's stain) and collagen fibers (Mallory's trichrome stain) were performed. The antioxidant effects of M. oleifera leaves were determined by measuring the reduced glutathione and lipid peroxidation product, malondialdehyde, in pancreatic tissue. M. oleifera treatment significantly ameliorated the altered FPG (from 380% to 145%), reduced glutathione (from 22% to 73%) and malondialdehyde (from 385% to 186%) compared to control levels. The histopathological damage of islet cells was also markedly reversed. Morphometrically, M. oleifera significantly increased the areas of positive purple modified Gomori stained β-cells (from 60% to 91%) and decreased the area percentage of collagen fibers (from 199% to 120%) compared to control values. Experimental findings clearly indicate the potential benefits of using the aqueous extract of M. oleifera leaves as a potent antidiabetic treatment.

  9. Depletion of T lymphocytes ameliorates cardiac fibrosis in streptozotocin-induced diabetic cardiomyopathy.

    PubMed

    Abdullah, Chowdhury S; Li, Zhao; Wang, Xiuqing; Jin, Zhu-Qiu

    2016-10-01

    T cell infiltration has been associated with increased coronary heart disease risk in patients with diabetes mellitus. Effect of modulation of T cell trafficking on diabetes-induced cardiac fibrosis has yet to be determined. Therefore, our aim was to investigate the circulatory T cell depletion-mediated cardioprotection in streptozotocin-induced diabetic cardiomyopathy. Fingolimod (FTY720), an immunomodulatory drug, was tested in wild-type (WT) C57BL/6 and recombination activating gene 1 (Rag1) knockout (KO) mice without mature lymphocytes in streptozotocin-induced type 1 diabetic model. FTY720 (0.3mg/kg/day) was administered intraperitoneally daily for the first 4weeks with interim 3weeks then resumed for another 4weeks in 11weeks study period. T lymphocyte counts, cardiac histology, function, and fibrosis were examined in diabetic both WT and KO mice. FTY720 reduced both CD4(+) and CD8(+) T cells in diabetic WT mice. FTY720-treated diabetic WT mouse myocardium showed reduction in CD3 T cell infiltration and decreased expression of S1P1 and TGF-β1 in cardiac tissue. Fibrosis was reduced after FTY720 treatment in diabetic WT mice. Rag1 KO mice exhibited no CD4(+) and CD8(+) T cells in the blood and CD3 T cells in the heart. Diabetic Rag1 KO mouse hearts appeared no fibrosis and exhibited preserved myocardial contractility. FTY720-induced antifibrosis was abolished in diabetic Rag1 KO mice. These findings demonstrate that chronic administration with FTY720 induces lymphopenia and protects diabetic hearts in WT mice whereas FTY720 increases cardiac fibrosis and myocardial dysfunction in diabetic Rag1 KO mice without mature lymphocytes.

  10. Rhinacanthus nasutus Ameliorates Cytosolic and Mitochondrial Enzyme Levels in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Visweswara Rao, Pasupuleti; Madhavi, K.; Dhananjaya Naidu, M.; Gan, Siew Hua

    2013-01-01

    The present study was conducted to evaluate the therapeutic efficacy of Rhinacanthus nasutus (R. nasutus) on mitochondrial and cytosolic enzymes in streptozotocin-induced diabetic rats. The rats were divided into five groups with 6 rats in each group. The methanolic extract of R. nasutus was orally administered at a dose of 200 mg/kg/day, and glibenclamide was administered at a dose of 50 mg/kg/day. All animals were treated for 30 days and were sacrificed. The activities of both intra- and extramitochondrial enzymes including glucose-6-phosphate dehydrogenase (G6PDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH) were measured in the livers of the animals. The levels of G6PDH, SDH, and GDH were significantly reduced in the diabetic rats but were significantly increased after 30 days of R. nasutus treatment. The increased LDH level in diabetic rats exhibited a significant reduction after treatment with R. nasutus. These results indicate that the administration of R. nasutus altered the activities of oxidative enzymes in a positive manner, indicating that R. nasutus improves mitochondrial energy production. Our data suggest that R. nasutus should be further explored for its role in the treatment of diabetes mellitus. PMID:23662138

  11. Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats.

    PubMed

    Barzegar-Fallah, Anita; Alimoradi, Houman; Asadi, Firouzeh; Dehpour, Ahmad Reza; Asgari, Mojgan; Shafiei, Massoumeh

    2015-04-01

    It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti-inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin-induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor-α were also determined. Streptozotocin-treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor-α, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor-α, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti-oxidative and anti-inflammatory mechanisms that appear

  12. Ameliorating effect of chromium administration on hepatic glucose metabolism in streptozotocin-induced experimental diabetes.

    PubMed

    Sundaram, Bhuvaneshwari; Singhal, Kirti; Sandhir, Rajat

    2012-01-01

    Chromium has been recognized as an essential trace element that plays an important role in carbohydrate metabolism. However, the molecular mechanisms involved in its action are not clear. This study was undertaken to understand the mechanism of chromium action in experimental diabetes. Streptozotocin-induced diabetic animals were administered chromium as chromium picolinate (CrP) at a daily dose of 1 mg/kg body weight for a period of 4 weeks. It was observed that chromium complexed with picolinate was effective in lowering plasma glucose levels as well as was able to alleviate polyphagia, polydipsia, and weight loss in diabetic animals. Administration of chromium was also found to normalize glycogen content in liver of diabetic animals to near control levels. The reduction in plasma glucose levels by chromium was accompanied by increase in activity of glycolytic enzymes (e.g., glucokinase, phosphofructokinase, and pyruvate kinase) and by suppression in activity of gluconeogenic enzymes (e.g., glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) in liver. Hepatic glucose uptake was found to be increased by chromium supplementation as demonstrated by decrease in Km and increase in Vmax values in diabetic animals. Chromium levels were lower in the liver of diabetic rats when compared with that of control rats. A negative correlation was observed between plasma glucose and chromium concentration in patients with diabetes. The data suggests that chromium supplementation as CrP is beneficial in correcting hyperglycemia, implying that the modulation of the glucose metabolism by chromium may be therapeutically beneficial in the treatment of diabetes.

  13. Catechin Treatment Ameliorates Diabetes and Its Complications in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh

    2017-01-01

    Context: Diabetes mellitus causes atherosclerosis and lipid abnormalities. Hypolipidemic and antioxidative properties of catechin (CTN) have been reported in several studies. Objective: This study assesses the possible protective effects of CTN against oxidative damage in the diabetic rats. Materials and Methods: The rats were divided into the control, untreated diabetic, and 3 CTN-treated diabetic groups (20, 40, and 80 mg/kg/d, intraperitoneal). The diabetic rats were induced by streptozotocin. Catechin was injected for 4 weeks. At the end of the experimental period, glucose, lipid profile, apoprotein A-I (apo A-I), apoprotein B (apo B), malondialdehyde (MDA) levels, and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in serum. Statistical analyses were performed using the InStat 3.0 program. Results: Streptozotocin caused an elevation of glucose, MDA, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apo B with reduction in high-density lipoprotein cholesterol (HDL-C), apo A-I, SOD, CAT, and GST in the serum (P < .05). The findings showed that the significant elevation in the body weight, glucose, MDA, TG, TC, LDL-C, and apo B and reduction in HDL-C, apo A-I, SOD, CAT, and GST were ameliorated in the CTN-treated diabetic groups versus the untreated group, in a dose-dependent manner (P < .05). Conclusion: The present investigation proposes that CTN may ameliorate diabetes and its complications by modification of oxidative stress. PMID:28228702

  14. Ursolic acid derivative ameliorates streptozotocin-induced diabestic bone deleterious effects in mice

    PubMed Central

    Yu, Su-Guo; Zhang, Cheng-Jie; Xu, Xiu-E; Sun, Ji-Hua; Zhang, Li; Yu, Peng-Fei

    2015-01-01

    Objective: This study was performed to investigate bone deteriorations of diabetic mice in response to the treatment of ursolic acid derivative (UAD). Methods: The biomarkers in serum and urine were measured, tibias were taken for the measurement on gene and protein expression and histomorphology analysis, and femurs were taken for the measurement on bone Ca and three-dimensional architecture of trabecular bone. Results: UAD showed a greater increase in bone Ca, BMD and significantly increased FGF-23 and OCN, reduced PTH and CTX in diabetic mice. UAD reversed STZ-induced trabecular deleterious effects and stimulated bone remodeling. The treatment of STZ group with UAD significantly elevated the ratio of OPG/RANKL. Moreover, insulin and IGF-1 showed a negative correlation with both FBG and Hb1Ac in STZ group. We attributed down-regulating the level of Hb1Ac in diabetic mice to that ursolic acid derivative could primely control blood sugar levels. After analyzing of two adipocyte markers, PPARγ and aP2, increased expression in the tibias of diabetic mice, and UAD could improve STZ-induced adipocyte dysfunction. Conclusions: These results demonstrated that UAD could ameliorate STZ-induced bone deterioration through improving adipocyte dysfunction and enhancing new bone formation and inhibiting absorptive function of osteoclast in the bone of diabetic mice. PMID:26097549

  15. Russelioside B, a pregnane glycoside ameliorates hyperglycemia in streptozotocin induced diabetic rats by regulating key enzymes of glucose metabolism.

    PubMed

    Abdel-Sattar, Essam; El-Maraghy, Shohda A; El-Dine, Riham Salah; Rizk, Sherine M

    2016-05-25

    An alternative strategy to treat diabetes mellitus is the use of various natural agents possessing hypoglycemic effect. Caralluma quadrangula has been used in Saudi traditional medicine in cases of thirst and hunger and for the treatment of diabetes. The present study was designed to evaluate the improving effect of russelioside B, a pregnane glycoside isolated from Caralluma quadrangula on glucose metabolism in the liver of streptozotocin-induced diabetic rats. Diabetes mellitus was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Experimental rats were administered russelioside B at a dose of 50 mg/kg body weight once a day for 30 days. The results showed that RB improved the fasting serum glucose level, glycated hemoglobin percent, serum insulin level and lipid profile. A significant improvement was observed upon the administration of russelioside B on the activities of the key enzymes of carbohydrate metabolism (glucokinase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and glycogen phosphorylase) in the liver of diabetic rats. Further, russelioside B administration to diabetic rats reverted gene expression of glucokinase, glucose-6-phosphatase, glycogen synthase and glycogen synthase kinase-3β to near normal levels. In conclusion, russelioside B possess antidiabetic and antihyperlipidemic effect in streptozotocin induced diabetic rats. Hence, administration of russelioside B may represent a potentially useful strategy for the management of diabetes.

  16. Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats.

    PubMed

    Niwa, Atsuko; Tajiri, Takashi; Higashino, Hideaki

    2011-05-01

    Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg(-1) d(-1)), Agaricus blazei (1 g kg(-1) d(-1)) or Smallanthus sonchifolius (4 g kg(-1) d(-1)) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass.

  17. Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats

    PubMed Central

    Niwa, Atsuko; Tajiri, Takashi; Higashino, Hideaki

    2011-01-01

    Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg−1 d−1), Agaricus blazei (1 g kg−1 d−1) or Smallanthus sonchifolius (4 g kg−1 d−1) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass. PMID:21562638

  18. Tyrosol, a phenolic compound, ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats.

    PubMed

    Chandramohan, Ramasamy; Pari, Leelavinothan; Rathinam, Ayyasamy; Sheikh, Bashir Ahmad

    2015-03-05

    The present study was designed to evaluate the effects of tyrosol, a phenolic compound, on the activities of key enzymes of carbohydrate metabolism in the control and streptozotocin-induced diabetic rats. Diabetes mellitus was induced in rats by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight). Experimental rats were administered tyrosol 1 ml intra gastrically at the doses of 5, 10 and 20mg/kg body weight and glibenclamide 1 ml at a dose of 600 μg/kg body weight once a day for 45 days. At the end of the experimental period, diabetic control rats exhibited significant (p<0.05) increase in plasma glucose, glycosylated hemoglobin with significant (p<0.05) decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism such as phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase were significantly (p<0.05) increased and the activities of hexokinase and glucose-6-phosphate dehydrogenase were significantly (p<0.05) decreased in the liver and kidney of diabetic control rats. Further, antioxidants were lowered in diabetic control rats. A significant (p<0.05) decline in glycogen level in the liver and muscle and glycogen synthase activity in the liver and a significant (p<0.05) increase in the activity of liver glycogen phosphorylase were observed in diabetic control rats compared to normal control rats. Oral administration of tyrosol to diabetic rats reversed all the above mentioned biochemical parameters to near normal in a dose dependent manner. Tyrosol at a dose of 20mg/kg body weight showed the highest significant effect than the other two doses. Immunohistochemical staining of pancreas revealed that tyrosol treated diabetic rats showed increased insulin immunoreactive β-cells, which confirmed the biochemical findings. The observed results were compared with glibenclamide, a standard oral hypoglycemic drug. The results of the present study suggest

  19. Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen.

    PubMed

    Kanasaki, Keizo; Shi, Sen; Kanasaki, Megumi; He, Jianhua; Nagai, Takako; Nakamura, Yuka; Ishigaki, Yasuhito; Kitada, Munehiro; Srivastava, Swayam Prakash; Koya, Daisuke

    2014-06-01

    Kidney fibrosis is the final common pathway of all progressive chronic kidney diseases, of which diabetic nephropathy is the leading cause. Endothelial-to-mesenchymal transition (EndMT) has emerged as one of the most important origins of matrix-producing fibroblasts. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been introduced into the market as antidiabetes drugs. Here, we found that the DPP-4 inhibitor linagliptin ameliorated kidney fibrosis in diabetic mice without altering the blood glucose levels associated with the inhibition of EndMT and the restoration of microRNA 29s. Streptozotocin-induced diabetic CD-1 mice exhibited kidney fibrosis and strong immunoreactivity for DPP-4 by 24 weeks after the onset of diabetes. At 20 weeks after the onset of diabetes, mice were treated with linagliptin for 4 weeks. Linagliptin-treated diabetic mice exhibited a suppression of DPP-4 activity/protein expression and an amelioration of kidney fibrosis associated with the inhibition of EndMT. The therapeutic effects of linagliptin on diabetic kidneys were associated with the suppression of profibrotic programs, as assessed by mRNA microarray analysis. We found that the induction of DPP-4 observed in diabetic kidneys may be associated with suppressed levels of microRNA 29s in diabetic mice; linagliptin restored microRNA 29s and suppressed DPP-4 protein levels. Using cultured endothelial cells, we found that linagliptin inhibited TGF-β2-induced EndMT, and such anti-EndMT effects of linagliptin were mediated through microRNA 29 induction. These results indicate the possible novel pleiotropic action of linagliptin to restore normal kidney function in diabetic patients with renal impairment.

  20. Dietary taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in streptozotocin-induced Sprague-Dawley rats.

    PubMed

    Yu, Xiaoping; Xu, Zhaoxia; Mi, Mantian; Xu, Hongxia; Zhu, Jundong; Wei, Na; Chen, Ka; Zhang, Qianyong; Zeng, Kaihong; Wang, Jian; Chen, Fang; Tang, Yong

    2008-03-01

    The purpose of this study was to investigate whether taurine ameliorate the diabetic retinopathy, and to further explore the underlying mechanisms. The Sprague-Dawley rats were injected with streptozotocin to establish experimental diabetic model, then fed without or with 1.2% taurine for additional 4-12 weeks. After that, the protective effects of dietary taurine supplementation on diabetic retinopathy were estimated. Our results showed that chronic taurine supplement effectively improved diabetic retinopathy as changes of histopathology and ultrastructure. The supplementation could not lower plasma glucose concentration (P > 0.05), but caused an elevation in taurine content and a decline in levels of glutamate and gamma-aminobutyric acid (GABA) in diabetic retina (P < 0.05). Moreover, chronic taurine supplementation increased glutamate transporter (GLAST) expression (P < 0.05), decreased intermediate filament glial fibrillary acidic protein (GFAP) and N-methyl-D: -aspartate receptor subunit 1 (NR1) expression in diabetic retina (P < 0.05). These results demonstrated that chronic taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in rats.

  1. Ameliorating effect of mother tincture of Syzygium jambolanum on carbohydrate and lipid metabolic disorders in streptozotocin-induced diabetic rat: Homeopathic remedy

    PubMed Central

    Maiti, Soumyajit; Ali, Kazi M.; Jana, Kishalay; Chatterjee, Kausik; De, Debasis; Ghosh, Debidas

    2013-01-01

    Background: Syzygium jambolanum (S jambolanum) is widely used in homeopathy for treating patients with diabetes mellitus. In the present study, an attempt has been made to investigate the remedial effect of homeopathic drug S jambolanum on carbohydrate and lipid metabolic disorders on streptozotocin induced diabetic rat. Materials and Methods: Diabetes induction in Wistar strain rat was performed as per standard method using streptozotocin at the dose of 4 mg/100 gm body weight. Activities of carbohydrate metabolic enzymes in hepatic tissue, and glycogen content in hepatic and muscular tissues were assessed biochemically following the standard protocols. Serum lipid profile level and activities of GOT and GPT in serum were measured as per standard method using specific kits. Results: The homeopathic drug, mother tincture of S jambolanum significantly decreased fasting blood glucose levels and improved carbohydrate metabolic key enzyme activities in hepatic tissue i.e., hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase in diabetic rats. Alongside, serum lipid profile biomarkers i.e., triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc) and high density lipoprotein cholesterol (HDLc) levels were significantly ameliorated in homeopathic drug supplemented diabetic animals in compared with the untreated diabetic animal. Side by side, the S jambolanum has the capacity to attenuate diabetes induced hepatic injury in model animal, which has been assessed here by the recovery of GOT and GPT activities in serum of drug treated diabetic animal. Conclusion: The result of the present study indicated that the homeopathic drug S jambolanum (mother tincture) has a protective effect on diabetic induced carbohydrate and lipid metabolic disorders in STZ-induced diabetic animal. PMID:23633838

  2. Klotho gene delivery ameliorates renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats by suppressing the Rho-associated coiled-coil kinase signaling pathway.

    PubMed

    Deng, Minghong; Luo, Yumei; Li, Yunkui; Yang, Qiuchen; Deng, Xiaoqin; Wu, Ping; Ma, Houxun

    2015-07-01

    The present study aimed to investigate whether klotho gene delivery attenuated renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats. A recombinant adeno-associated virus (rAAV) carrying mouse klotho full-length cDNA (rAAV.mKL), was constructed for in vivo investigation of klotho expression. Diabetes was induced in rats by a single tail vein injection of 60 mg/kg streptozotocin. Subsequently, the diabetic rats received an intravenous injection of rAAV.mKL, rAAV.green fluorescent protein (GFP) or phosphate-buffered saline (PBS). The Sprague-Dawley rat group received PBS and served as the control group. After 12 weeks, all the rats were sacrificed and ELISA, immunohistochemical and histological analyses, fluorescence microscopy, semi-quantitative reverse transcription-polymerase chain reaction and western blottin were performed. A single dose of rAAV.mKL was found to prevent the progression of renal hypertrophy and fibrosis for at least 12 weeks (duration of study). Klotho expression was suppressed in the diabetic rats, but was increased by rAAV.mKL delivery. rAAV.mKL significantly suppressed diabetes-induced renal hypertrophy and histopathological changes, reduced renal collagen fiber generation and decreased kidney hypertrophy index. In addition, rAAV.mKL decreased the protein expression levels of fibronectin and vimentin, while it downregulated the mRNA expression and activity of Rho-associated coiled-coil kinase (ROCK)I in the kidneys of the diabetic rats. These results indicated that klotho gene delivery ameliorated renal hypertrophy and fibrosis in diabetic rats, possibly by suppressing the ROCK signaling pathway. This may offer a novel approach for the long-term control and renoprotection of diabetes.

  3. Amelioration of pancreatic and renal derangements in streptozotocin-induced diabetic rats by polyphenol extracts of Ginger (Zingiber officinale) rhizome.

    PubMed

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin

    2015-12-01

    Free and bound polyphenol extracts of Zingiber officinale rhizome were investigated for their antidiabetic potential in the pancreatic and renal tissues of diabetic rats at a dose of 500mg/kg body weight. Forty Wistar rats were completely randomized into five groups: A-E consisting of eight animals each. Group A (control) comprises normal healthy animals and were orally administered 1.0mL distilled water on a daily basis for 42 days while group B-E were made up of 50mg/kg streptozotocin (STZ)-induced diabetic rats. Group C and D received 1.0mL 500mg/kg body weight free and bound polyphenol extracts respectively while group E received 1.0mL 0.6mg/kg of glibenclamide. Administration of the extracts to the diabetic rats significantly reduced (p<0.05) serum glucose and urea concentrations, increased (p<0.05) serum insulin and Homeostatic Model Assessment for β-cell dysfunction (HOMA-β) while the level of creatinine and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were not affected. Histological examination of the pancreas and kidney revealed restoration of the structural derangements caused by streptozotocin in the polyphenol extracts treated diabetic rats compared to the control groups. Therefore, polyphenols from Zingiber officinale could ameliorate diabetes-induced pancreatic and renal derangements in rats.

  4. Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Srinivasan, Subramani; Sathish, Gajendren; Jayanthi, Mahadevan; Muthukumaran, Jayachandran; Muruganathan, Udaiyar; Ramachandran, Vinayagam

    2014-01-01

    Epidemiological studies have demonstrated that diabetes mellitus is a serious health burden for both governments and healthcare providers. This study was hypothesized to evaluate the antihyperglycemic potential of eugenol by determine the activities of key enzymes of glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg body weight (b.w.)). Eugenol was administered to diabetic rats intragastrically at 2.5, 5, and 10 mg/kg b.w. for 30 days. The dose 10 mg/kg b.w. significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and liver marker enzymes (AST, ALT, and ALP), creatine kinase and blood urea nitrogen in serum and blood of diabetic rats were significantly reverted to near normal levels by the administration of eugenol. Further, eugenol administration to diabetic rats improved body weight and hepatic glycogen content demonstrated the antihyperglycemic potential of eugenol in diabetic rats. The present findings suggest that eugenol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes, and it is sensible to broaden the scale of use of eugenol in a trial to alleviate the adverse effects of diabetes.

  5. Antioxidant-Rich Extract from Plantaginis Semen Ameliorates Diabetic Retinal Injury in a Streptozotocin-Induced Diabetic Rat Model

    PubMed Central

    Tzeng, Thing-Fong; Liu, Wayne Young; Liou, Shorong-Shii; Hong, Tang-Yao; Liu, I-Min

    2016-01-01

    Plantaginis semen, the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd. (Plantaginaceae), has been traditionally used to treat blurred vision in Asia. The aim of this work was to investigate the effect of plantaginis semen ethanol extract (PSEE) on the amelioration of diabetic retinopathy (DR) in streptozotocin (STZ)-diabetic rats. PSEE has abundant polyphenols with strong antioxidant activity. PSEE (100, 200 or 300 mg/kg) was oral administrated to the diabetic rats once daily consecutively for 8 weeks. Oral administration of PSEE resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and retinal vascular permeability and leukostasis in diabetic rats. In addition, PSEE administration increased the activities of superoxidase dismutase (SOD) and catalase (CAT), and glutathione peroxidase (GSH) level in diabetic retinae. PSEE treatment inhibited the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) and the phosphorylation of Akt without altering the Akt protein expression in diabetic retinae. PSEE not only down-regulated the gene expression of hypoxia-inducible factor-1α (TNF-α) and interleukin-1β (IL-1β), but also reduced ICAM-1 and VCAM-1 expression in diabetic retinae. Moreover, PSEE reduced the nuclear factor-κB (NF-κB) activation and corrected imbalance between histone deacetylases (HDAC) and histone acetyltransferases (HAT) activities in diabetic retinae. In conclusion, phenolic antioxidants extract from plantaginis semen has potential benefits in the prevention and/or progression of DR. PMID:27649243

  6. Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes.

    PubMed

    Bhutada, Pravinkumar; Mundhada, Yogita; Bansod, Kuldeep; Tawari, Santosh; Patil, Shaktipal; Dixit, Pankaj; Umathe, Sudhir; Mundhada, Dharmendra

    2011-06-20

    Memory impairment induced by streptozotocin in rats is a consequence of changes in CNS that are secondary to chronic hyperglycemia, impaired oxidative stress, cholinergic dysfunction, and changes in glucagon-like peptide (GLP). Treatment with antihyperglycemics, antioxidants, and cholinergic agonists are reported to produce beneficial effect in this model. Berberine, an isoquinoline alkaloid is reported to exhibit anti-diabetic and antioxidant effect, acetylcholinesterase (AChE) inhibitor, and increases GLP release. However, no report is available on influence of berberine on streptozotocin-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., twice daily, 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. In another set of experiment, berberine (100mg/kg) treatment during training trials also improved learning and memory, lowered hyperglycemia, oxidative stress, and ChE activity. Chronic treatment (30 days) with vitamin C or metformin, and donepezil during training trials also improved diabetes-induced memory impairment and reduced oxidative stress and/or choline esterase activity. In conclusion, the present study demonstrates treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in diabetic rats.

  7. Extract of Ginkgo Biloba Ameliorates Streptozotocin-Induced Type 1 Diabetes Mellitus and High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice.

    PubMed

    Rhee, Ki-Jong; Lee, Chang Gun; Kim, Sung Woo; Gim, Dong-Hyeon; Kim, Hyun-Cheol; Jung, Bae Dong

    2015-01-01

    Diabetes mellitus (DM) is caused by either destruction of pancreatic β-cells (type 1 DM) or unresponsiveness to insulin (type 2 DM). Conventional therapies for diabetes mellitus have been developed but still needs improvement. Many diabetic patients have complemented conventional therapy with alternative methods including oral supplementation of natural products. In this study, we assessed whether Ginkgo biloba extract (EGb) 761 could provide beneficial effects in the streptozotocin-induced type 1 DM and high-fat diet-induced type 2 DM murine model system. For the type 1 DM model, streptozotocin-induced mice were orally administered EGb 761 for 10 days prior to streptozotocin injection and then again administered EGb 761 for an additional 10 days. Streptozotocin-treated mice administered EGb 761 exhibited lower blood triglyceride levels, lower blood glucose levels and higher blood insulin levels compared to streptozotocin-treated mice. Furthermore, liver LPL and liver PPAR-α were increased whereas IL-1β and TNF-α were decreased in streptozotocin-injected mice treated with EGb 761 compared to mice injected with streptozotocin alone. For the type 2 DM model, mice were given high-fat diet for 60 days and then orally administered EGb 761 every other day for 80 days. We found that mice given a high-fat diet and EGb 761 showed decreased blood triglyceride levels, increased liver LPL, increased liver PPAR-α and decreased body weight compared to mice given high-fat diet alone. These results suggest that EGb 761 can exert protective effects in both type 1 and type 2 DM murine models.

  8. Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice.

    PubMed

    Perez Gutierrez, Rosa Martha; Madrigales Ahuatzi, Diana; Horcacitas, Maria Del Carmen; Garcia Baez, Efren; Cruz Victoria, Teresa; Mota-Flores, Jose Maria

    2014-01-01

    Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.

  9. Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Perez Gutierrez, Rosa Martha; Madrigales Ahuatzi, Diana; Horcacitas, Maria del Carmen; Garcia Baez, Efren; Cruz Victoria, Teresa; Mota-Flores, Jose Maria

    2014-01-01

    Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis. PMID:24523819

  10. Pyrroloquinoline quinone (PQQ) has potential to ameliorate streptozotocin-induced diabetes mellitus and oxidative stress in mice: A histopathological and biochemical study.

    PubMed

    Kumar, Narendra; Kar, Anand

    2015-10-05

    Enhanced oxidative stress and hyperglycemia are associated with diabetes mellitus (DM). As pyrroloquinoline quinone (PQQ) is known to protect cells from oxidative stress, the present study was undertaken to reveal the hitherto unknown effects of PQQ in DM and associated problems in different tissues. Forty two mice were randomly divided into six groups. Group I receiving only citrate buffer served as the normal control, while group II animals were injected with citrate buffer and PQQ at 20 mg/kg for 15 days and served as test drug control. Animals of groups III-VI were rendered diabetic by single dose of streptozotocin (STZ, 150 mg/kg body weight), following which PQQ at a dose of 5, 10 and 20 mg/kg, was injected to the animals of group IV, V and VI respectively for 15 days. At the end, alterations in serum indices such as glucose, different lipids, insulin, amylase, urea, uric acid, serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase; tissue antioxidants and histopathological alterations in liver, kidney and pancreas were evaluated. STZ-treated animals developed oxidative stress as indicated by a significant increase in tissue lipid peroxidation (LPO) and lipid hydroperoxide, serum glucose, total cholesterol, triglyceride and urea, with a parallel decrease in the levels of serum insulin and tissue antioxidants. When diabetic animals received different doses of PQQ, these adverse effects were ameliorated. However, 20 mg/kg of PQQ appeared to be most effective. Findings revealed for the first time that PQQ has the potential to mitigate STZ-induced DM and oxidative damage in different organs of mice, suggesting that it may ameliorate diabetes mellitus and associated problems.

  11. Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer’s rat model

    PubMed Central

    Guo, Zhangyu; Chen, Yanxing; Mao, Yan-Fang; Zheng, Tingting; Jiang, Yasi; Yan, Yaping; Yin, Xinzhen; Zhang, Baorong

    2017-01-01

    Recent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer’s disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting. We observed cognitive deficits, tau hyperphosphorylation, and neuroinflammation in the brains of ICV-STZ rats. Intranasal insulin treatment for 6 weeks significantly improved cognitive function, attenuated the level of tau hyperphosphorylation, ameliorated microglial activation, and enhanced neurogenesis in ICV-STZ rats. Additionally, our results indicate that intranasal delivery of insulin probably attenuates tau hyperphosphorylation through the down-regulation of ERK1/2 and CaMKII in the brains of ICV-STZ rats. Our findings demonstrate a beneficial effect of intranasal insulin and provide the mechanistic basis for treating AD patients with intranasal insulin. PMID:28382978

  12. Antidiabetic efficacy of citronellol, a citrus monoterpene by ameliorating the hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Srinivasan, Subramani; Muruganathan, Udaiyar

    2016-04-25

    Diabetes mellitus is a clinically complex disease characterized by chronic hyperglycemia with metabolic disturbances. During diabetes, endogenous hepatic glucose production is increased as a result of impaired activities of the key enzymes of carbohydrate metabolism. The purpose of the present study was to evaluate the antidiabetic efficacy of citronellol, a citrus monoterpene in streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (40 mg/kg b.w). STZ induced diabetic rats received citronellol orally at the doses of 25, 50, and 100 mg/kg b.w for 30 days. In this study the levels of plasma glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA1C), glycogen, and the activities of carbohydrate metabolic enzymes, liver and kidney markers were evaluated. Oral administration of citronellol (50 mg/kg) for 30 days dose dependently improved the levels of insulin, Hb and hepatic glycogen with significant decrease in glucose and HbA1C levels. The altered activities of carbohydrate metabolic enzymes, hepatic and kidney markers were restored to near normal. Citronellol supplement was found to be effective in preserving the normal histological appearance of hepatic cells and insulin-positive β-cells in STZ-rats. Our results suggest that administration of citronellol attenuates the hyperglycemia in the STZ-induced diabetic rats by ameliorating the key carbohydrate metabolic enzymes and could be developed as a functional and nutraceutical ingredient in combating diabetes mellitus.

  13. Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats.

    PubMed

    Kim, Dae-Young; Jung, Sun-Young; Kim, Kijeong; Kim, Chang-Ju

    2016-08-01

    Diabetes mellitus is considered as a risk factor for Alzheimer disease. The aim of the present study was to evaluate the possibility whether treadmill exercise ameliorates Alzheimer disease-associated memory loss in the diabetes mellitus. For this study, the effects of treadmill exercise on short-term memory and spatial learning ability in relation with Wnt signaling pathway were evaluated using the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ. Step-down avoidance task and 8-arm radial maze test were performed for the memory function. Immunohistochemistry for 5-bro-mo-2'-deoxyridine (BrdU) and doublecortin (DCX) and Western blot for Wnt3 and glycogen synthase kinase-3β (GSK-3β) were conducted. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. In the present results, short-term memory and spatial learning ability were deteriorated by induction of diabetes. Treadmill exercise improved short-term memory and spatial learning ability in the diabetic rats. The numbers of BrdU-positive and DCX-positive cells in the hippocampal dentate gyrus were decreased by induction of diabetes. Treadmill exercise increased these numbers in the diabetic rats. Wnt3 expression in the hippocampus was decreased and GSK-3β expression in the hippocampus was increased by induction of diabetes. Treadmill exercise increased Wnt3 expression and suppressed GSK-3β expression in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats.

  14. Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats

    PubMed Central

    Kim, Dae-Young; Jung, Sun-Young; Kim, Kijeong; Kim, Chang-Ju

    2016-01-01

    Diabetes mellitus is considered as a risk factor for Alzheimer disease. The aim of the present study was to evaluate the possibility whether treadmill exercise ameliorates Alzheimer disease-associated memory loss in the diabetes mellitus. For this study, the effects of treadmill exercise on short-term memory and spatial learning ability in relation with Wnt signaling pathway were evaluated using the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ. Step-down avoidance task and 8-arm radial maze test were performed for the memory function. Immunohistochemistry for 5-bro-mo-2′-deoxyridine (BrdU) and doublecortin (DCX) and Western blot for Wnt3 and glycogen synthase kinase-3β (GSK-3β) were conducted. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. In the present results, short-term memory and spatial learning ability were deteriorated by induction of diabetes. Treadmill exercise improved short-term memory and spatial learning ability in the diabetic rats. The numbers of BrdU-positive and DCX-positive cells in the hippocampal dentate gyrus were decreased by induction of diabetes. Treadmill exercise increased these numbers in the diabetic rats. Wnt3 expression in the hippocampus was decreased and GSK-3β expression in the hippocampus was increased by induction of diabetes. Treadmill exercise increased Wnt3 expression and suppressed GSK-3β expression in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats. PMID:27656623

  15. Compound A, a selective glucocorticoid receptor agonist, inhibits immunoinflammatory diabetes, induced by multiple low doses of streptozotocin in mice

    PubMed Central

    Saksida, T; Vujicic, M; Nikolic, I; Stojanovic, I; Haegeman, G; Stosic-Grujicic, S

    2014-01-01

    Background and Purpose Type 1 diabetes is a multifactorial inflammatory disease that develops as a result of deregulated immune responses, causing progressive autoimmune destruction of insulin-producing beta cells of pancreas. 2-((4-acetoxyphenyl)-2-chloro-N-methyl) ethylammonium chloride, compound A (CpdA), is a selective glucocorticoid receptor (GR) agonist that displays strong anti-inflammatory and immunomodulatory activities. We investigated the therapeutic effectiveness of CpdA in a pharmacological model of type 1 diabetes in mice. Experimental Approach The utility of CpdA in diabetes prevention was evaluated in vivo through its prophylactic administration to male C57BL/6 mice that received multiple low doses of streptozotocin for immunoinflammatory diabetes induction. The effect of CpdA on disease development was studied by measuring blood glucose and insulin level, histopathological examination, determination of the nature of infiltrating cells, pro- and anti-inflammatory cytokine production, and signalling pathways. Key Results Prophylactic in vivo therapy with CpdA conferred protection against development of immunoinflammatory diabetes in mice by dampening the M1/Th1/Th17 immune response and switching it towards an anti-inflammatory M2/Th2/Treg profile, thus preserving beta cell function. Conclusions and Implications Anti-diabetic properties of CpdA are mediated through modulation of immune cell-mediated pathways, but without triggering adverse events. These findings provide basic information for the therapeutic use of selective GR agonists in the amelioration of islet-directed autoimmunity. PMID:25158597

  16. Tripterygium Glycosides Tablet Ameliorates Renal Tubulointerstitial Fibrosis via the Toll-Like Receptor 4/Nuclear Factor Kappa B Signaling Pathway in High-Fat Diet Fed and Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ma, Ze-jun; Zhang, Xiao-na; Li, Li; Yang, Wei; Wang, Shan-shan; Guo, Xin; Sun, Pei; Chen, Li-ming

    2015-01-01

    Tripterygium glycosides tablet (TGT) is a Chinese traditional medicine that has been shown to protect podocytes from injury and reduce the proteinuria. The aim of this study was to assess the effect of TGT on renal tubulointerstitial fibrosis and its potential mechanism in high-fat diet fed and STZ-induced diabetic rats. Rats were randomly divided into normal control rats (NC group), diabetic rats without drug treatment (DM group), and diabetic rats treated with TGT (1, 3, or 6 mg/kg/day, respectively) for 8 weeks. The results showed that 24 h proteinuria and urinary N-acetyl-glucosaminidase (NAG) in diabetic rats were decreased by TGT treatment without affecting blood glucose. Masson's trichrome stains showed that apparent renal tubulointerstitial fibrosis was found in DM group, which was ameliorated by TGT treatment. The expression of α-SMA was significantly decreased, accompanied by increased expression of E-cadherin in TGT-treated rats, but not in untreated DM rats. Further studies showed that TGT administration markedly reduced expression of TLR4, NF-κB, IL-1β, and MCP-1 in TGT-treated diabetic rats. These results showed that TGT could ameliorate renal tubulointerstitial fibrosis, the mechanism which may be at least partly associated with the amelioration of EMT through suppression of the TLR4/NF-κB pathway. PMID:26347890

  17. Therapeutic effect of Acacia nilotica pods extract on streptozotocin induced diabetic nephropathy in rat.

    PubMed

    Omara, Enayat A; Nada, Somaia A; Farrag, Abdel Razik H; Sharaf, Walid M; El-Toumy, Sayed A

    2012-09-15

    The aim of the present study was to examine the effect of aqueous methanol extract (150 and 300 mg/kg body weight) of Acacia nilotica pods in streptozotocin-induced diabetic rats for 60 days, and its biochemical, histopathological and histochemical study in the kidney tissues. Diabetic rats exhibited hyperglycemia, elevated of serum urea and creatinine. Significant increase in lipid peroxidation (LPO), superoxide dismutase (SOD) and reduced glutathione (GSH) was observed in diabetic kidney. Histopathological examination revealed infiltration of the lymphocytes in the interstitial spaces, glomerular hypertrophy, basement membrane thickening and tubular necrosis with loss of their brush border in some of the proximal convoluted tubules in diabetic rats. Acacia nilotica extract lowered blood glucose levels, restored serum urea and creatinine. In addition, Acacia nilotica extract attenuated the adverse effect of diabetes on LPO, SOD and GSH activity. Treatment with Acacia nilotica was found to almost restore the normal histopathological architecture of kidney of streptozotocin-induced diabetic rats. However, glomerular size and damaged area showed ameliorative effect after treatment with the extract. In conclusion, the antioxidant and antihyperglycemic properties of Acacia nilotica extract may offer a potential therapeutic source for the treatment of diabetes.

  18. Perindopril treatment in streptozotocin induced diabetic nephropaty.

    PubMed

    Trojacanec, J; Zafirov, D; Labacevski, N; Jakjovski, K; Zdravkovski, P; Trojacanec, P; Petrusevska, G

    2013-01-01

    Diabetic nephropathy (DN) is one of the most common causes of terminal stadium damage to the kidneys. The angiotensin-converting enzyme (ACE) represents a significant risk factor for the progression of DN. ACE inhibitors are medications of particular interest knowing the role of angiotensin II in the development of DN. This study aimed to examine the effects of ACE inhibitor treatment perindopril (PER), administered to rats with streptozotocin (STZ) induced DN, that developed albuminuria, renal hypertrophy and mild glomerulussclerosis. DN was induced by a STZ (60 mg/kg ip) single injection to normotensive Wistar rats. The administration of STZ caused diabetes mellitus (DM) with symptoms and signs of DN including poor general condition, body-weight loss, kidney weight increase as well as increased values of BUN and serum creatinine, accompanied by increased diuresis as well as distinct albuminuria. The majority of these symptoms were manifested 4 weeks after, and even more distinctly 8 and 12 weeks after administering STZ. The perindopril treatment (6 mg/kg BW), starting 4 weeks after administering STZ, resulted in a significant improvement of all symptoms and signs of DN, significantly lowering the values of BUN and serum creatinine, albuminuria and diuresis. The histopathological examination of the renal samples at 8 and 12 weeks after the beginning of the study have shown that perindopril significantly lowers the progression of glomerulopathy, and significantly improves the glomerulosclerotic index, as well as the progression of renal histological abnormalities induced with STZ. Thus perindopril treatment ameliorates STZ-induced nephropathic changes in DM rats.

  19. The Hypoglycemic and Antioxidant Activity of Cress Seed and Cinnamon on Streptozotocin Induced Diabetes in Male Rats

    PubMed Central

    Qusti, Safaa; Balashram, Sarah A.

    2016-01-01

    The present study aimed to estimate the stimulation of pancreas of rats with streptozotocin induced diabetes using 20% (w/w) garden cress seed (Lepidium sativum) and cinnamon methanol extracts. The positive control diabetic group showed a significant increase in fasting blood sugar, lipid peroxide, interleukin-6, carboxymethyl lysine, serum uric acid, urea, creatinine, immunoglobulins, and urine albumin and a significant decrease in antioxidant enzymes, sodium ions, potassium ions, and urine creatinine. Severe histopathological changes in the kidney and pancreas tissues in hyperglycemic rats were also shown in the positive control diabetic group. Meanwhile, the groups that were treated with 20% garden cress seed and cinnamon methanol extracts showed a significant decrease in fasting blood sugar and all elevated abovementioned biochemical parameters and an increase in the lowered ones restoring them nearly to the normal levels of G1. Kidney and pancreas tissues were also ameliorated and restored nearly to the normal status. Both garden cress seed and cinnamon methanol extracts succeeded in controlling hyperglycemia in rats with streptozotocin induced diabetes and ameliorated the biochemical and histopathological changes because of their antioxidant activity acquired by their possession of phenolic phytochemicals. PMID:27525022

  20. Zinc supplementation alleviates hyperglycemia and associated metabolic abnormalities in streptozotocin-induced diabetic rats.

    PubMed

    Barman, Susmita; Srinivasan, Krishnapura

    2016-12-01

    The cause and effect relationship between diabetes and zinc is complex and unclear. This animal study has examined the potential of zinc supplementation in beneficial modulating hyperglycemia, insulin secretion, and metabolic abnormalities associated with diabetes. The study was conducted in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats were subjected to dietary interventions for 6 weeks with zinc supplementation (5 times and 10 times the normal level). Supplemental-zinc-fed diabetic groups showed significant control on hyperglycemia and hypoinsulinemia. There was a significant reduction in protein glycosylation, glucosuria, and urinary excretion of proteins and urea in diabetic animals maintained on a zinc-supplemented diet. Diabetic rats showed significantly higher plasma albumin and lower plasma urea and creatinine levels upon zinc supplementation. Significant alterations in insulin sensitivity indices HOMA-IR, HOMA-B, and QUICKI were also indicated by zinc supplementation. The pathological abnormalities in pancreatic islets of diabetic animals were significantly alleviated by dietary zinc intervention. This study provides the first evidence that zinc supplementation can partially ameliorate the severity of diabetic hyperglycemia and associated metabolic abnormalities, hypoinsulinemia, insulin resistance, and altered pancreatic morphology. Thus, zinc supplementation may offer a significant potential for clinical application in managing diabetic hyperglycemia and related metabolic complications.

  1. Effect of bitter gourd (Momordica charantia) on glycaemic status in streptozotocin induced diabetic rats.

    PubMed

    Shetty, A K; Kumar, G Suresh; Sambaiah, K; Salimath, P V

    2005-09-01

    Bitter gourd (Momordica charantia), a commonly consumed vegetable is used as an adjunct in the management of diabetes mellitus. A study was carried out to examine the effect of edible portion of bitter gourd at 10% level in the diet in streptozotocin induced diabetic rats. To evaluate the glycaemic control of bitter gourd during diabetes, diet intake, gain in body weight, water intake, urine sugar, urine volume, glomerular filtration rate and fasting blood glucose profiles were monitored. Water consumption, urine volume and urine sugar were significantly higher in diabetic controls compared to normal rats and bitter gourd feeding alleviated this rise during diabetes by about 30%. Renal hypertrophy was higher in diabetic controls and bitter gourd supplementation, partially, but effectively prevented it (38%) during diabetes. Increased glomerular filtration rate in diabetes was significantly reduced (27%) by bitter gourd. An amelioration of about 30% in fasting blood glucose was observed with bitter gourd feeding in diabetic rats. These results clearly provided experimental evidence that dried bitter gourd powder in the diet at 10% level improved diabetic status signifying its beneficial effect during diabetes.

  2. Protease-activated receptor-1 deficiency protects against streptozotocin-induced diabetic nephropathy in mice

    PubMed Central

    Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, C. Arnold

    2016-01-01

    Endogenously administered activated protein C ameliorates diabetic nephropathy (DN) in a protease-activated receptor-1 (PAR-1)-dependent manner, suggesting that PAR-1 activation limits the progression of DN. Activation of PAR-1 in fibroblast-like cells, however, induces proliferation and extracellular matrix production, thereby driving fibrotic disease. Considering the key role of mesangial proliferation and extracellular matrix production during DN, PAR-1 may in fact potentiate diabetes-induced kidney injury. To determine the net effect of PAR-1 in DN, streptozotocin-induced DN was studied in wild type and PAR-1 deficient mice. Subsequent mechanistic insight was obtained by assessing profibrotic responses of mesangial and tubular epithelial cells in vitro, following PAR-1 stimulation and inhibition. Despite having similar glucose levels, PAR-1 deficient mice developed less kidney damage after induction of diabetes, as evidenced by diminished proteinuria, plasma cystatin C levels, expansion of the mesangial area, and tubular atrophy. In vitro, PAR-1 signaling in mesangial cells led to increased proliferation and expression of matrix proteins fibronectin and collagen IV. Conversely, a reduction in both proliferation and fibronectin deposition was observed in diabetic PAR-1 deficient mice. Overall, we show that PAR-1 plays an important role in the development of DN and PAR-1 might therefore be an attractive therapeutic target to pursue in DN. PMID:27618774

  3. Downstream modulation of extrinsic apoptotic pathway in streptozotocin-induced Alzheimer's dementia in rats: Erythropoietin versus curcumin.

    PubMed

    Samy, Doaa M; Ismail, Cherine A; Nassra, Rasha A; Zeitoun, Teshreen M; Nomair, Azhar M

    2016-01-05

    Erythropoietin and curcumin showed promising neuroprotective effects in various models of Alzheimer's dementia. This study was designed to compare the beneficial effects of erythropoietin and/or curcumin in intracerebro-ventricular (ICV) streptozotocin-induced Alzheimer's like disease in rats. Rats received ICV injection of either saline (control, n=8 rats), or streptozotocin. Three weeks following surgery, streptozotocin-injected rats were assigned into 4 groups (8 rats each); vehicle, curcumin (80mg/kg/day, orally), erythropoietin (500 IU/kg every other day, intraperitoneally) and combined (curcumin and erythropoietin)-treated groups. After 3 months of treatment, rats were subjected to neurobehavioral testing, and then killed for biochemical and histological assessment of hippocampus. Fas ligand protein and caspase-8 activity as mediators of extrinsic apoptotic pathway, oxidative stress markers (malondialdehyde and reduced glutathione) and β-amyloid (1-40 and 1-42) peptides were measured. The results showed that administration of erythropoietin suppressed extrinsic apoptosis better than curcumin, while curcumin was more effective in combating oxidative stress in ICV-streptozotocin injected rats. Both erythropoietin and curcumin treatments (individually or combined) equally reduced the hippocampal β-amyloid accumulation and improved cognitive impairment in Morris water maze and passive avoidance tasks. The combined treatment was the most effective in ameliorating apoptosis and oxidative stress rather than behavioral responses or β-amyloid burden. In conclusion, ICV-streptozotocin-induced Alzheimer's dementia activates hippocampal Fas ligand-mediated apoptosis, which could be reduced by erythropoietin and/or curcumin treatment. Curcumin supplementation alone could ameliorate cognitive deficits and reverse biochemical alterations in ICV-streptozotocin Alzheimer's rat model without the hazardous polycythemic effect of long-term erythropoietin injection.

  4. Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

    PubMed Central

    Damasceno, D. C.; Netto, A. O.; Iessi, I. L.; Gallego, F. Q.; Corvino, S. B.; Dallaqua, B.; Sinzato, Y. K.; Bueno, A.; Calderon, I. M. P.; Rudge, M. V. C.

    2014-01-01

    Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis. PMID:24977161

  5. The Antidiabetic Activity of Nigella sativa and Propolis on Streptozotocin-Induced Diabetes and Diabetic Nephropathy in Male Rats

    PubMed Central

    Al-Seeni, Madeha N.; Bakhashwain, Amal S.

    2017-01-01

    This study was conducted to compare the ameliorative effect of Nigella sativa and propolis methanol extract on streptozotocin-induced diabetic male rats and treating diabetic nephropathy. Forty male Albino rats were divided into four groups; the first group was the negative control fed standard diet. The other 30 rats were injected with streptozotocin to induce diabetes by a single intravenous injection and then divided equally into three groups; the second group was the positive diabetic control; the third and the fourth groups were treated orally with 20% w/w Nigella sativa seeds methanol extract and propolis methanol extract (20% w/w), respectively. The rats of the second group showed increased glucose levels and lipid peroxide accompanied with reduction in superoxide dismutase, catalase, and glutathione-S-transferase enzyme activities compared with the negative control. Carboxymethyl lysine, interleukin-6, and immunoglobulins were also increased as a result of diabetes. Kidney function parameters were also elevated, while potassium and sodium levels were decreased. Moreover, tissues of kidney and pancreas showed severe histopathological changes. Treating the diabetic rats with Nigella sativa and propolis methanol extract in the third and fourth groups, respectively, ameliorated all altered biochemical and pathological examinations approaching the negative control. Propolis was more effective than Nigella sativa. PMID:28298934

  6. Antihyperglycemic and antilipidperoxidative effects ofTephrosia purpurea seed extract in streptozotocin induced diabetic rats.

    PubMed

    Pavana, P; Sethupathy, S; Manoharan, S

    2007-03-01

    The aim of the present study was to evaluate the antihyperglycemic and antilipidperoxidative effects of ethanolic seed extract ofTephrosia purpurea (TpEt) in streptozotocin induced diabetic rats. Hyperglycemia associated with an altered hexokinase and glucose 6 phosphatase activities, elevated lipid peroxidation, disturbed enzymatic and non-enzymatic antioxidants status were observed in streptozotocin induced diabetic rats. Oral administration of "TpEt" at a dose of 300mg/kg bw showed significant antihyperglcemic and antilipidperoxidative effects as well as increased the activities of enzymatic antioxidants and levels of non enzymatic antioxidants. We also noticed that the antihyperglycemic effect of plant drug (TpEt) was comparable to that of the reference drug glibenclamide. Our results clearly indicate that "TpEt" has potent antihyperglycemic and antilipidperoxidative effects in streptozotocin induced diabetic rats and therefore further studies are warranted to isolate and characterize the bioactive antidiabetic principles from "TpEt".

  7. Oxygen free-radical scavengers and immune destruction of murine islets in allograft rejection and multiple low-dose streptozocin-induced insulitis.

    PubMed

    Mendola, J; Wright, J R; Lacy, P E

    1989-03-01

    We examined the effects of desferrioxamine (DFX), a potent inhibitor of the formation of oxygen-derived hydroxyl radicals, and nicotinamide (NIC), a poly(ADP-ribose) synthetase inhibitor and a weak free-radical scavenger, on two models of immune destruction of murine islets [i.e., allograft rejection and multiple low-dose streptozocin (STZ)-induced insulitis]. Freshly isolated or low-temperature-cultured BALB/cJ islets were transplanted beneath the kidney capsules of C57BL/6J recipients. The recipients were treated with NIC alone (500 mg.kg-1.day-1), DFX alone (4.2 mg/day x 14 days), or NIC + DFX. Only recipients treated with NIC + DFX, receiving cultured islets, showed a mean graft survival time significantly longer than control mice receiving freshly isolated or cultured islets. Control CD-1 mice treated with multiple low doses of STZ developed insulitis and diabetes. Treatment with NIC alone, DFX alone, or NIC + DFX decreased the severity of hyperglycemia relative to the controls. Treatment with DFX alone was more effective than NIC alone or NIC + DFX. Only the group treated with DFX alone had a lower incidence of diabetes (mean plasma glucose level greater than 200 mg/dl) than the controls after 4 wk. Histologically, islets from control mice showed severe insulitis, islet destruction, and absence of stainable insulin, whereas islets from DFX-treated mice showed only mild peri-insulitis and a relative preservation of beta-cell granulation. Our study showed that NIC and DFX partially protect islets from immune destruction in allograft rejection and in low-dose STZ-induced insulitis. Apparently, hydroxyl radicals play important roles in both of these models.

  8. Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats.

    PubMed

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

    2013-01-01

    This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg) diabetic rats significantly reduced (P < 0.05) the fasting blood glucose compared to control groups. There was significant increase (P < 0.05) in the antioxidant enzymes activities in the animals treated with both polyphenols. Similarly, the polyphenols normalised the activities of some carbohydrate metabolic enzymes (hexokinase and phosphofructokinase) in the liver of the rats treated with it and significantly reduced (P < 0.05) the activities of liver function enzymes. The results from the present study have shown that both free and bound polyphenols from Z. officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians.

  9. Bitter gourd (Momordica charantia) modulates activities of intestinal and renal disaccharidases in streptozotocin-induced diabetic rats.

    PubMed

    Kumar Shetty, Ajaya; Suresh Kumar, Gurusiddaiah; Veerayya Salimath, Paramahans

    2005-08-01

    During diabetes, structural and functional changes in the alimentary tract are known to take place resulting in increased absorption of intestinal glucose and alterations in the activities of brush border disaccharidases. Similar observations are also reported in the renal cortex. In the present investigation, we examined the effect of feeding bitter gourd fruit devoid of seeds on activities of intestinal and renal disaccharidases, viz., maltase, sucrase, and lactase in streptozotocin-induced diabetic rats. Normal and diabetic rats were fed either with basal diet or a diet containing 10% bitter gourd powder. Specific activities of intestinal disaccharidases were significantly increased during diabetes, and supplementing bitter gourd in the diet clearly indicated amelioration in the activities of maltase and lactase during diabetes. However, a significant change was not observed with sucrase activity by feeding of bitter gourd. During diabetes, renal disaccharidase activities were significantly lower than those in the control rats. Bitter gourd supplementation was beneficial in alleviating the reduction in maltase activity during diabetes. However, not much change in the activities of sucrase and lactase was observed upon feeding. This positive influence of feeding bitter gourd on intestinal and renal disaccharidases clearly indicates their beneficial role in the management of diabetes, thus making diabetic animals more tolerant to hyperglycemia.

  10. Modulatory effect of bitter gourd (Momordica charantia LINN.) on alterations in kidney heparan sulfate in streptozotocin-induced diabetic rats.

    PubMed

    Kumar, G Suresh; Shetty, A K; Salimath, P V

    2008-01-17

    Glycoconjugates in the kidney play an important role in the maintenance of glomerular filtration barrier. Thickening of the glomerular basement membrane (GBM) is well characterized in diabetic nephropathy. Changes in GBM mainly include reduction and undersulfation of heparan sulfate, and laminin with accumulation of type IV collagen leading to kidney dysfunction and there is a need to identify therapies that arrest disease progression to end-stage renal failure. In the present investigation, effect of bitter gourd on streptozotocin-induced diabetic rats with particular emphasis on kidney heparan sulfate (HS) was studied. Earlier, our study showed partial reversal of all the diabetes-induced effects by bitter gourd. Increase in the components of glycoconjugates during diabetes was significantly decreased by bitter gourd feeding. Diabetes associated elevation in the activities of enzymes involved in the synthesis and degradation of glycosaminoglycans (GAGs) were significantly lowered by bitter gourd supplementation. GAGs composition revealed decrease in amino sugar, and uronic acid contents during diabetes and bitter gourd feeding was effective in countering this reduction. Decrease in sulfate content in the GAGs during diabetes was ameliorated by bitter gourd feeding. HS decreased by 43% in diabetic rats while bitter gourd feeding to diabetic rats showed 28% reduction. These results clearly indicate beneficial role of bitter gourd in controlling glycoconjugate and heparan sulfate related kidney complications during diabetes thus prolonging late complications of diabetes.

  11. Brugia malayi soluble and excretory-secretory proteins attenuate development of streptozotocin-induced type 1 diabetes in mice.

    PubMed

    Amdare, N; Khatri, V; Yadav, R S P; Tarnekar, A; Goswami, K; Reddy, M V R

    2015-12-01

    Understanding the modulation of the host-immune system by pathogens-like filarial parasites offers an alternate approach to prevent autoimmune diseases. In this study, we have shown that treatment with filarial proteins prior to or after the clinical onset of streptozotocin-induced type-1 diabetes (T1D) can ameliorate the severity of disease in BALB/c mice. Pre-treatment with Brugia malayi adult soluble (Bm A S) or microfilarial excretory-secretory (Bm mf ES) or microfilarial soluble (Bm mf S) antigens followed by induction of diabetes led to lowering of fasting blood glucose levels with as many as 57.5-62.5% of mice remaining nondiabetic. These proteins were more effective when they were used to treat the mice with established T1D as 62.5-71.5% of the mice turned to be nondiabetic. Histopathological examination of pancreas of treated mice showed minor inflammatory changes in pancreatic islet cell architecture. The therapeutic effect was found to be associated with the decreased production of cytokines TNF-α & IFN-γ and increased production of IL-10 in the culture supernatants of splenocytes of treated mice. A switch in the production of anti-insulin antibodies from IgG2a to IgG1 isotype was also seen. Together these results provide a proof towards utilizing the filarial derived proteins as novel anti-diabetic therapeutics.

  12. Dendrobium officinale Kimura et Migo attenuates diabetic cardiomyopathy through inhibiting oxidative stress, inflammation and fibrosis in streptozotocin-induced mice.

    PubMed

    Zhang, Zhihao; Zhang, Duoduo; Dou, Mengmeng; Li, Zhubo; Zhang, Jie; Zhao, Xiaoyan

    2016-12-01

    Dendrobium officinale Kimura et Migo (Dendrobium catenatum Lindley), a prized traditional Chinese Medicine, has been used in China and Southeast Asian countries for centuries. The present study was aimed to investigate the effects and the possible mechanisms of the Dendrobium officinale extracts (DOE) on diabetic cardiomyopathy in mice. The diabetic model was induced by intraperitoneal injection of streptozotocin at the dose of 50mg/kg body weight for 5 consecutive days. After 8 weeks treatment of DOE, mice were sacrificed, blood sample and heart tissues were collected. Our results showed that Streptozotocin-induced diabetic model was effectively achieved and serum CK and LDH levels were significantly increased in mice with diabetic cardiomyopathy. Pretreatment with DOE decreased the heart-to-body weight ratio (HW/BW) and showed an evident hypoglycemic effect. DOE pretreatment significantly decreased CK, LDH, TC and TG levels, limited the production of MDA and increased the activities of T-SOD. The histological analysis of Oil red O staining and Sirius red staining showed an obvious amelioration of cardiac injury, inhibition of cardiac lipid accumulation and deposition of collagen when pretreatment with DOE. In addition, Western blot detection and analysis showed that DOE down-regulated the expression of TGF-β, collegan-1, fibronectin, NF-κB, TNF-α and IL-1β. In conclusion, our study suggested that DOE possesses the cardioprotective potential against diabetic cardiomyopathy, which may be due to the inhibition of oxidative stress, cardiac lipid accumulation, pro-inflammatory cytokines and cardiac fibrosis.

  13. Use of unripe plantain (Musa paradisiaca) in the management of diabetes and hepatic dysfunction in streptozotocin induced diabetes in rats

    PubMed Central

    Okafor, Polycarp

    2015-01-01

    Aim This study aims to investigate the effect of unripe plantain (Musa paradisiaca) on markers of hepatic dysfunction in streptozotocin induced diabetic rats. Methods Blood glucose; relative liver weight (RLW); relative kidney weight (RKW); relative heart weight (RHW); relative pancreatic weight (RPW); serum and hepatic serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP); serum amylase, lipase, total, and conjugated bilirubin; and chemical analysis of the test feed were determined using standard techniques. Results The diabetic rats had significant alteration (P < 0.05) of blood glucose; RLW; RKW; RPW; serum and hepatic AST, ALT, and ALP; serum total and conjugated bilirubin; and serum lipase activities compared with nondiabetic while these parameters were significantly improved (P < 0.05) in the rats fed unripe plantain. There were no significant differences (P > 0.05) in the RHW of the rats in the three groups, as well as significant decreases (P < 0.05) in the amylase levels of the diabetic rats compared with the nondiabetic, but there was nonsignificant increase (P > 0.05) in the amylase levels of the rats fed unripe plantain compared with the nondiabetic rats. The test and standard rat feeds contained considerable amount of proteins, carbohydrates, fats, phenols, and crude fiber. Conclusion Amelioration of acute pancreatitis by unripe plantain could play a key role in its management of diabetes and related complications. PMID:25838921

  14. Extract of Sesbania grandiflora Ameliorates Hyperglycemia in High Fat Diet-Streptozotocin Induced Experimental Diabetes Mellitus

    PubMed Central

    Panigrahi, Ghanshyam; Panda, Chhayakanta; Patra, Arjun

    2016-01-01

    Background. Sesbania grandiflora has been traditionally used as antidiabetic, antioxidant, antipyretic, and expectorant and in the management of various ailments. Materials and Methods. The study evaluates the antidiabetic activity of methanolic extract of Sesbania grandiflora (MESG) in type 2 diabetic rats induced by low dose streptozotocine and high fat diet. Diabetic rats were given vehicle, MESG (200 and 400 mg/kg, p.o.), and the standard drug, metformin (10 mg/kg), for 28 days. During the experimental period, body weight, abdominal girth, food intake, fasting serum glucose, urine analyses were measured. Insulin tolerance test was carried out on 25th day of drug treatment period. Serum analyses for lipid profile and SGOT and SGPT and serums creatinine, urea, protein, SOD, and MDA were also carried out. At the end of the experiment, animals were euthanized, the liver and pancreas were immediately dissected out, and the ratio of pancreas to body weight and hepatic glycogen were calculated. Results. MESG (200 and 400 mg/kg, p.o.) induced significant reduction (P < 0.05) of raised blood glucose levels in diabetic rats and also restored other parameters to normal level. Conclusion. Therefore, it is concluded that MESG has potential antihyperglycemic and antihyperlipemic activities and alleviate insulin resistance conditions. PMID:27313954

  15. Chronic administration of atorvastatin could partially ameliorate erectile function in streptozotocin-induced diabetic rats

    PubMed Central

    Park, Juhyun; Kwon, Oh Seong; Cho, Sung Yong; Paick, Jae-Seung; Kim, Soo Woong

    2017-01-01

    The efficacy of statins is related to the ‘common soil’ hypothesis, which proposes oxidative stress and inflammation as main pathophysiologic processes in the disease group of diabetes and endothelial dysfunction. This study evaluated the recovery of erectile function after administration of chronic statin alone in streptozotocin (STZ)-induced diabetes mellitus (DM) rats, focusing on the anti-oxidative effects and consequentially recuperated endothelial function. A total of 45 male Sprague-Dawley rats (8 weeks old) were divided into three groups (n = 15 each): an age-matched normal control group (Control group), an uncontrolled DM group (DM group), and a statin-treated group (Statin group). The rats in the DM and Statin group received an injection of STZ (60 mg/kg). Beginning 10 weeks after the establishment of DM, the Statin group received daily treatment with atorvastatin (10 mg/kg) via oral gavage for four weeks. After 14 weeks, the results of the experiment were evaluated. The ratios of intracavernosal pressure (ICP) to mean arterial pressure (MAP) were recorded with cavernosometry (20 Hz, 3 V, 0.2 msec for 30 seconds) before and after the intravenous administration of udenafil (1 mg/kg). Expression of alpha-smooth muscle actin (α-SMA) was evaluated using cavernosal tissue. In addition, changes in RhoA translocation ratio and myosin phosphatase target subunit 1 (MYPT1) phosphorylation were evaluated with western blot. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also analyzed as measurements of oxidative stress levels. The ICP/MAP and area under the curve (AUC)/MAP ratios of the Statin group were obviously superior to the DM group, but were not comparable to the Control group (P<0.001). The level of oxidative stress, namely SOD activity, was also significantly lower in the Statin group than in the DM group (P = 0.015), and was comparable to the Control group. In contrast, MDA levels were not considerably different among the groups (P = 0.217). The RhoA translocation ratio was not significantly different among the groups (P = 0.668), whereas MYPT1 phosphorylation in the Statin group was significantly lower than in the DM group (P = 0.030), and similar to the Control group. Expression of α-SMA in the Statin group was higher than in the DM group (P<0.001), and comparable to the Control group. Chronic statin treatment alone showed anti-oxidative effects and helped to restore the erectile mechanism, but did not lead to the full recovery of erectile function in STZ-induced DM rats. Therefore, combination therapy rather than a single agent should be the preferred treatment strategy for DM-associated erectile dysfunction, especially in the setting of severe diabetes. PMID:28245261

  16. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats.

    PubMed

    Elbe, H; Vardi, N; Esrefoglu, M; Ates, B; Yologlu, S; Taskapan, C

    2015-01-01

    The role of oxygen radicals are known for the pathogenesis of kidney damage. The aim of the present study was to investigate the antioxidative effects of melatonin, quercetin, and resveratrol on streptozotocin (STZ)-induced diabetic nephropathy in rats. A total of 35 male Wistar rats were divided into 5 groups as follows: control, diabetes mellitus (DM), DM + melatonin, DM + quercetin, and DM + resveratrol. All the injections started on the same day of single-dose STZ injection and continued for 30 days. At the end of this period, kidneys were removed and processed for routine histological procedures. Biochemical parameters and morphological changes were examined. In DM group, blood glucose levels were significantly increased, whereas body weights were decreased compared with the control group. Significant increases in blood urea nitrogen and tissue malondialdehyde (MDA) levels and decreases in superoxide dismutase and catalase activities were detected in DM group. Administration of melatonin, quercetin, and resveratrol significantly reduced these values. Melatonin was more efficient in reducing MDA levels than other antioxidants (p < 0.05). STZ-induced histopathological alterations including epithelial desquamation, swelling, intracytoplasmic vacuolization, brush border loss and peritubular infiltration. Additionally, basement membrane thickening and sclerotic changes were observed in glomerulus. Transforming growth factor-β1 positive cells were also increased. Melatonin, quercetin, and resveratrol significantly reduced these histopathological changes. Our results indicate that melatonin, quercetin, and resveratrol might be helpful in reducing diabetes-induced renal damage.

  17. Melatonin intake since weaning ameliorates steroidogenic function and sperm motility of streptozotocin-induced diabetic rats.

    PubMed

    da Costa, C F P; Gobbo, M G; Taboga, S R; Pinto-Fochi, M E; Góes, R M

    2016-05-01

    Melatonin may be used as an antioxidant in therapy against systemic sequelae caused by oxidative stress in diabetes. However, as melatonin has a major role in regulating reproductive activity, its consequence on reproductive parameters under diabetes needs to be better clarified. We have studied whether prior and concomitant treatment of juvenile Wistar rats with low doses of melatonin interferes in reproductive damage induced by experimental diabetes after 1 and 8 weeks. The consequences of melatonin administration since weaning on reproductive parameters of healthy rats at adulthood were also evaluated. Melatonin was provided in drinking water (10 μg/kg b.w./day) after weaning (5-week-old). Diabetes was induced by streptozotocin injection (4.5 mg/100 g b.w.) at 13-week-old rats, and rats were euthanized 1 and 8 weeks after disease onset. Diabetes decreased circulating testosterone levels (~35% to 1 week; ~62% to 2 months; p < 0.01) but did not affect testes sperm counts. Two months of diabetes reduced the sperm reserve and led to atrophy of epididymal cauda. Both 1-week and 2-month diabetes impaired sperm motility, decreased the number of spermatozoa with progressive movement, and increased the number of immotile sperm. Melatonin intake reduced serum testosterone levels ~29% in healthy 14-week-old and ~23% in 21-week-old rats and reduced daily testicular sperm production ~26% in the latter disease stage, but did not interfere in sperm reserves and transit time for both experimental periods. Exogenous melatonin prevented the serum testosterone decrease and damage to sperm motility in diabetic rats and attenuated reduction in sperm counts and transit time induced by 1-week diabetes but did not avoid this decrease at 2-month diabetes. Low doses of melatonin administered prior to and during experimental diabetes attenuated damage to testicular steroidogenic activity and preserved sperm motility, but not sperm reserves in the rat. Our data indicated a differential action of melatonin in normoglycemic and hyperglycemic conditions, particularly in sperm motility and testosterone production by Leydig cells.

  18. Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice.

    PubMed

    Pachauri, Shakti D; Verma, Priya Ranjan P; Dwivedi, Anil K; Tota, Santoshkumar; Khandelwal, Kiran; Saxena, Jitendra K; Nath, Chandishwar

    2013-08-01

    This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action.

  19. Antihyperglycemic and antihyperlipidemic effects of Tephrosia purpurea leaf extract in streptozotocin induced diabetic rats.

    PubMed

    Pavana, P; Manoharan, S; Renju, G L; Sethupathy, S

    2007-10-01

    Diabetes mellitus is a worldwide leading metabolic syndrome, associated with profound alterations in carbohydrate, lipids, lipoproteins and protein metabolisms. Worldwide, traditional practitioners for the treatment of diabetes and its complications use a wide variety of medicinal plants. In the present study the aqueous extract of Tephrosia purpurea leaves (TpALet) was evaluated for its antihyperglycemic and antihyperlipidemic effects in streptozotocin induced diabetic rats. Profound alterations in the concentrations of blood glucose, lipids and lipoproteins were observed in diabetic rats. Oral administration of TpALet to diabetic rats at a dose of 600 mg/kg body weight significantly reduced the level of blood glucose and increased the level of plasma insulin as well as normalized the lipids and lipoproteins profile. The present study thus demonstrated that TpALet has prominent antihyperglycemic and antihyperlipidemic effects in streptozotocin induced diabetic rats.

  20. Quantitative study of the myenteric plexus of the stomach of rats with streptozotocin-induced diabetes.

    PubMed

    Fregonesi, C E; Miranda-Neto, M H; Molinari, S L; Zanoni, J N

    2001-03-01

    The purpose of the present study was to investigate the morphological and quantitative alterations of the myenteric plexus neurons of the stomach of rats with streptozotocin-induced chronic diabetes and compare them to those of non-diabetic animals. Samples from the body of the stomach were used for whole-mount preparations stained with NADH-diaphorase and for histological sections stained with hematoxylin-eosin. It was observed that diabetes cause a significant decrease on the number of neurons.

  1. Hypoglycemic effect of Aloe vera gel on streptozotocin-induced diabetes in experimental rats.

    PubMed

    Rajasekaran, S; Sivagnanam, K; Ravi, K; Subramanian, S

    2004-01-01

    In the present study an attempt has been made to evaluate the presence of hypoglycemic activity in the alcoholic extract of Aloe vera gel. Effects of oral administration of A. vera extract at a concentration of 200 and 300 mg/kg of body weight on (a) normal fasted rats, (b) oral glucose-loaded rats, and (c) streptozotocin-induced diabetic rats have been studied. A. vera extract maintain the glucose homeostasis by controlling the carbohydrate metabolizing enzymes.

  2. Therapeutic Effects of Bupleurum Polysaccharides in Streptozotocin Induced Diabetic Mice

    PubMed Central

    Li, Hong; Liu, Zhenzhen; Xu, Yanyan; Zhou, Chunjiao; Lu, Xiaoxiao; Su, Xiaoyu; Zhang, Yunyi; Chen, Daofeng

    2015-01-01

    Diabetes mellitus is related to low-grade chronic inflammation and oxidative stress. Bupleurum Polysaccharides (BPs), isolated from Bupleurum smithii var. parvifolium has anti-inflammatory and anti-oxidative properties. However, little is known about its therapeutic effects on diabetes. In this experiment, the effects of BPs on alleviation of diabetes and the underlying mechanisms were investigated. Diabetic mice model was established via successive intraperitoneal injections of streptozotocin (100 mg/kg body weight) for two days. Mice with blood glucose levels higher than 16.8mmol/L were selected for experiments. The diabetic mice were orally administered with BPs (30 and 60 mg/kg) once a day for 35 days. BPs not only significantly decreased levels of blood glucose, but also increased those of serum insulin and liver glycogen in diabetic mice compared to model mice. Additionally, BPs adminstration improved the insulin expression and suppressed the apoptosis in pancreas of the diabetic mice. Histopathological observations further demonstrated that BPs protected the pancreas and liver from oxidative and inflammatory damages. These results suggest that BPs protect pancreatic β cells and liver hepatocytes and ameliorate diabetes, which is associated with its anti-oxidative and anti-inflammatory properties. PMID:26176625

  3. Antidiabetic effect of Merremia emarginata Burm. F. in streptozotocin induced diabetic rats

    PubMed Central

    Gandhi, G Rajiv; Sasikumar, P

    2012-01-01

    Objective To investigate the antidiabetic property of Merremia emarginata (M. emarginata) Burm. F. plant in streptozotocin induced diabetic rats. Methods The dose dependent effects of 28 days oral treatment with methanol extract (100, 200 and 400 mg/kg) from the plant of M. emarginata on blood glucose level, body weight, insulin, total hemoglobin, glycosylated haemoglobin (HbA1C), total protein, serum urea, serum creatinine and carbohydrate metabolizing enzymes were evaluated in streptozotocin induced diabetic rats. Histology of pancreas was also studied. Results A significant decrease in blood glucose, serum urea and serum creatinine and significant increase in body weight, insulin and protein level were observed in diabetic rats treated with M. emarginata. Treatment with M. emarginata resulted in a significant reduction of HbA1C and an increase in total hemoglobin level. The activities of carbohydrate metabolizing enzymes such as hexokinase were significantly increased whereas glucose-6-phosphatase, fructose-1, 6-bisphosphatase were significantly decreased by the administration of M. emarginata in diabetic rats. Histology of diabetic rats treated with M. emarginata showed the pancreatic β-cells regeneration. Conclusions These findings suggest that M. emarginata has potent antidiabetic activity in streptozotocin induced diabetic rats. PMID:23569914

  4. Antihyperlipidemic Effect of Peucedanum Pastinacifolium Extract in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Movahedian, Ahmad; Zolfaghari, Behzad; Sajjadi, S. Ebrahim; Moknatjou, Reza

    2010-01-01

    INTRODUCTION: Dyslipidemia is one of the most common complications of diabetes mellitus, significantly contributing to cardiovascular morbidity and mortality in diabetic patients. Peucedanum pastinacifolium Boiss. & Hausskn. is commonly used as an antihyperlipidemic vegetable in Iranian folk medicine. MATERIAL AND METHODS: In this study, we examined a hydroalcoholic extract of the aerial parts of Peucedanum pastinacifolium to determine its lipid-lowering activity in normal and streptozotocin (STZ)-induced diabetic rats. Experimental diabetes mellitus was induced by a single intraperitoneal administration of streptozotocin. Normal and streptozotocin-induced diabetic rats were separated into four groups. The groups were fed with 0, 125, 250 or 500 mg/kg body weight of Peucedanum Pastinacifolium hydroalcoholic Extract (PPE) in aqueous solution for 30 days. RESULTS: The results show that there were significant (P < 0.05) increases in total serum cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in streptozotocin-induced diabetic rats. Treatment of diabetic rats with PPE over a period of a month returned these levels close to control levels. CONCLUSION: These results suggest that PPE has hypolipidemic effects in streptozotocin-induced diabetic rats. PMID:20613940

  5. Edaravone attenuates intracerebroventricular streptozotocin-induced cognitive impairment in rats.

    PubMed

    Reeta, K H; Singh, Devendra; Gupta, Yogendra K

    2017-02-15

    Alzheimer's disease is a major cause of dementia worldwide. Edaravone, a potent free radical scavenger, is reported to be neuroprotective. The present study was designed to investigate the effect of chronic edaravone administration on intracerebroventricular-streptozotocin (ICV-STZ) induced cognitive impairment in male Wistar rats. Cognitive impairment was developed by single ICV-STZ (3 mg/kg) injection bilaterally on day 1. Edaravone (1, 3 and 10 mg/kg, orally, once daily) was administered for 28 days. Morris water maze and passive avoidance tests were used to assess cognitive functions at baseline and on days 14 and 28. ICV-STZ caused cognitive impairment as evidenced by increased escape latency and decreased time spent in target quadrant in the Morris water maze test and reduced retention latency in the passive avoidance test. STZ caused increase in oxidative stress, cholinesterases, inflammatory cytokines and protein expression of ROCK-II and decrease in protein expression of ChAT. Edaravone ameliorated the STZ-induced cognitive impairment. STZ-induced increase in oxidative stress and increased levels of pro-inflammatory cytokines (TNF-α, IL-1β) were mitigated by edaravone. Edaravone also prevented STZ-induced increased protein expression of ROCK-II. Moreover, edaravone significantly prevented STZ-induced increased activity of cholinesterases in the cortex and hippocampus. The decreased expression of ChAT caused by STZ was brought towards normal by edaravone in the hippocampus. The results thus show that edaravone is protective against STZ-induced cognitive impairment, oxidative stress, cholinergic dysfunction and altered protein expressions. This study thus suggests the potential of edaravone as an adjuvant in the treatment of Alzheimer's disease.

  6. Prevention of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice by an extract from gum resin of Boswellia serrata (BE).

    PubMed

    Shehata, Ahmed M; Quintanilla-Fend, L; Bettio, Sabrina; Singh, C B; Ammon, H P T

    2011-09-15

    Type 1-diabetes is an autoimmune disease, where a chronic inflammatory process finally causes β-cell death and insulin deficiency. Extracts from gum resin of Boswellia serrata (BE) have been shown to posses anti-inflammatory properties especially by targeting factors/mediators related to autoimmune diseases. Multiple low dose-streptozotocin (MLD-STZ) treatment is a method to induce diabetes in animals similar to Type 1 diabetes in humans. It was aimed to study whether or not a BE could prevent hyperglycemia, inflammation of pancreatic islets and increase of proinflammatory cytokines in the blood in MLD-STZ treated mice. In BK+/+ wild type mice, 5 days of daily treatment with 40 mg/kg STZ i.p. produced permanent increase of blood glucose, infiltration of lymphocytes into pancreatic islets (CD3-stain), apoptosis of periinsular cells (staining for activated caspase 3) after 10 days as well as shrinking of islet tissue after 35 days (H&E staining). This was associated with an increase of granulocyte colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF) and proinflammatory cytokines (IL-1A, IL-1B, IL-2, IL-6, IFN-γ, TNF-α) in the blood. Whereas BE alone did not affect blood glucose in non diabetic mice, in STZ treated mice simultaneous i.p. injection of 150 mg/kg of BE over 10 days prevented animals from increase of blood glucose levels. Histochemical studies showed, that i.p. injection of 150 mg/kg BE for 10 days starting with STZ treatment, avoided lymphocyte infiltration into islets, apoptosis of periinsular cells and shrinking of islet size 35 days after STZ. As far as the cytokines tested are concerned, there was a significant inhibition of the increase of G-CSF and GM-CSF. BE also significantly prevented the increase of IL-1A, IL-1B, IL-2, IL-6, IFN-γ and TNF-α. It is concluded that extracts from the gum resin of Boswellia serrata prevent islet destruction and consequent hyperglycemia in an animal model of type 1

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

    PubMed

    Hu, Xiaolei; Zhang, Xiaomei; Jin, Guoxi; Shi, Zhaoming; Sun, Weihua; Chen, Fengling

    2017-02-01

    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.

  8. Low-power laser irradiation in salivary glands reduces glycemia in streptozotocin-induced diabetic female rats.

    PubMed

    Fukuoka, Cíntia Yuki; Torres Schröter, Gabriella; Nicolau, José; Simões, Alyne

    2016-12-01

    Low-power laser irradiation (LPLI) has been extensively employed to modulate inflammation in vitro and in vivo. Previous reports from our group indicated that LPLI might regulate glycemia in diabetic animals. Diabetes results in chronic hyperglycemia and therefore chronic inflammation by upregulation of inflammatory markers such as the high mobility group box 1 (HMGB1) protein. Thus this study aimed to analyze the LPLI effects upon blood glucose levels, plasma insulin and HMGB1 concentrations in a diabetes experimental rat model. Streptozotocin-induced diabetic rats were irradiated in the salivary glands area with a diode laser applied at 660 nm, 70 mW, 20 J/cm(2) , 22.4 J, with a spot area of 0.028 cm(2) and its effects were evaluated. LPLI significantly reduced diabetic rat hyperglycemia, without changing insulin or HMGB1 plasma levels, but possibly by ameliorating the insulin resistance in these animals. These findings suggest that LPLI might have a systemic effect, but more studies are necessary to better understand its mechanisms. Fasting blood glucose measured by peroxidase-glucose oxidase (PGO) method (A), showing a reduction of diabetic animals glycemia after LPLI. LPLI probably reduced the hyperglycemia in diabetes by improving the insulin resistance in these animals (B). C n = 10, CL n = 10, D n = 7 and DL n = 8. Data are expressed as mean ± SD; * P < 0.05 vs. respective control group; # P < 0.05 vs. D group.

  9. Hypoglycemic Effect of Calotropis gigantea Linn. Leaves and Flowers in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Rathod, Nanu R; Chitme, Havagiray R; Irchhaiya, Raghuveer; Chandra, Ramesh

    2011-01-01

    Objectives To evaluate the hypoglycemic and anti-diabetic activity of chloroform extract of Calotropis gigantea leaves and flowers in normal rats and streptozotocin induced diabetes. Methods The hypoglycemic activity in normal rats was carried out by treatment using chloroform extract of Calotropis gigantea leaf and flower 10, 20 and 50 mg/kg, orally. The oral glucose tolerance test was carried out by administering glucose (2 g/kg, p.o), to non-diabetic rats treated with leaf and flowers extracts at oral doses 10, 20 and 50 mg/kg, p.o and glibenclamide 10 mg/kg. The serum glucose was then measured at 0, 1.5, 3 and 5 hr after administration of extracts/drug. Streptozotocin-induced diabetic rats were administered the same doses of leaf and flower extracts, and standard drugs glibenclamide was given to the normal rats or 0.5 ml of 5% Tween-80, for 27 days. The blood sample from all groups collected by retro-orbital puncture on 7, 14, 21 and 27th days after administration of the extracts/drug and used for the estimation of serum glucose levels using the glucose kit. Results The Calotropis gigantea leaves and flowers extracts were effective in lowering serum glucose levels in normal rats. Improvement in oral glucose tolerance was also registered by treatment with Calotropis gigantean. The administration of leaf and flower extracts to streptozotocin-induced diabetic rats showed a significant reduction in serum glucose levels. Conclusion It is concluded that chloroform extracts of Calotropis gigantea leaves and flowers have significant anti-diabetic activity. PMID:22043394

  10. Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats.

    PubMed

    Kristová, V; Lísková, S; Sotníková, R; Vojtko, R; Kurtanský, A

    2008-01-01

    Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increased cardiovascular risk is accompanied with diabetes-induced endothelial dysfunction. Pharmacological agents with endothelium-protective effects may decrease cardiovascular complications. In present study sulodexide (glycosaminoglycans composed from heparin-like and dermatan fractions) was chosen to evaluate its protective properties on endothelial dysfunction in diabetes. Effect of sulodexide treatment (SLX, 100 UI/kg/day, i.p.) in 5 and 10 weeks lasting streptozotocin-induced diabetes (30 mg/kg/day, i.p. administered for three consecutive days) was investigated. Animals were divided into four groups: control (injected with saline solution), control-treated with sulodexide (SLX), diabetic (DM) and diabetic-treated with sulodexide (DM+SLX). The pre-prandial and postprandial plasma glucose levels, number of circulating endothelial cells (EC) and acetylcholine-induced relaxation of isolated aorta and mesenteric artery were evaluated. Streptozotocin elicited hyperglycemia irrespective of SLX treatment. Streptozotocin-induced diabetes enhanced the number of circulating endothelial cells compared to controls. SLX treatment decreased the number of EC in 10-week diabetes. Acetylcholine-induced relaxation of mesenteric arteries was significantly impaired in 5 and 10-week diabetes. SLX administration improved relaxation to acetylcholine in 5 and 10-week diabetes. Diabetes impaired acetylcholine-induced relaxation of rat aorta irrespective of SLX treatment. Our results demonstrate that SLX treatment lowers the number of circulating endothelial cells and improves endothelium-dependent relaxation in small arteries. These findings suggest endothelium-protective effect of sulodexide in streptozotocin-induced diabetes.

  11. Effect of Evolvulus alsinoides on lipid metabolism of streptozotocin induced diabetic rats

    PubMed Central

    Gomathi, Duraisamy; Ravikumar, Ganesan; Kalaiselvi, Manokaran; Devaki, Kanakasabapathi; Uma, Chandrasekar

    2013-01-01

    Objective To determine the effect of ethanolic extract of Evolvulus alsinoides (E. alsinoides) on diabetes-induced changes in lipid metabolism. Methods The ethanolic extract of E. alsinoides on serum and tissue lipid levels were examined in control and experimental group rats. Results Oral administration of E. alsinoides extract to streptozotocin induced diabetic rats for 45 d significantly reduced the levels of triglycerids, phospholipids, cholesterol and free fatty acids in serum and tissues, it increases the high density lipoprotein in serum as that of control. Conclusions The ethanolic extract of E. alsinoides supplementation is useful in hyperlipidemia prevention during diabetes mellitus.

  12. Antidiabetic activity of aqueous leaf extract of Atriplex halimus L. (Chenopodiaceae) in streptozotocin-induced diabetic rats

    PubMed Central

    Chikhi, Ilyas; Allali, Hocine; Dib, Mohamed El Amine; Medjdoub, Houria; Tabti, Boufeldja

    2014-01-01

    Objective To investigate the antidiabetic effect of A. halimus leaf in streptozotocin-induced diabetic rats. Methods The aqueous extract of the plant leaf was tested for its efficacy in streptozotocin-induced diabetic rats. The extract was evaluated for its acute and short term general toxicity in male mice and for its antihyperglycemic activity using glucose tolerance test in rats. The aqueous extract was subjected to phytochemical screening and determination of total phenolic contents. Results The statistical data indicated the significant increase in the body weight and decrease in the blood glucose and hepatic levels. The total protein level was significantly increased when treated with the extract. Conclusions These results suggest that the aqueous leaf extract of A. halimus has beneficial effects in reducing the elevated blood glucose level and hepatic levels in streptozotocin-induced diabetic rats.

  13. Effects of Tephrosia purpurea aqueous seed extract on blood glucose and antioxidant enzyme activities in streptozotocin induced diabetic rats.

    PubMed

    Pavana, P; Sethupathy, S; Santha, K; Manoharan, S

    2008-10-25

    The aim of the present study was to evaluate the effects of aqueous seed extract of Tephrosia purpurea (TpASet) on blood glucose and antioxidant status in streptozotocin induced diabetic rats. Hyperglycemia associated with an altered hexokinase and glucose-6-phosphatase activities, elevated lipid peroxidation, disturbed enzymatic [Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] and non enzymatic [Glutathione, vitamin C and vitamin E] antioxidant status were observed in streptozotocin induced diabetic rats. Oral administration of "TpASet" at a dose of 600 mg/kg body weight showed significant improvement in above mentioned parameters. Our results clearly indicate that "TpASet" has potent antihyperglycemic and antioxidant effects in streptozotocin-induced diabetic rats and therefore further studies are warranted to isolate and characterize the bioactive principles from "TpASet".

  14. Antioxidant properties of Momordica Charantia (bitter gourd) seeds on Streptozotocin induced diabetic rats.

    PubMed

    Sathishsekar, Dhanasekar; Subramanian, Sorimuthu

    2005-01-01

    The aim of the present study is to investigate the antioxidant activities of the aqueous extract of seeds of two varieties, namely a country and hybrid variety of Momordica charantia (MCSEt1 and MCSEt2) respectively in streptozotocin induced diabetic rats. Oral administration of both the seed extracts at a concentration of 150 mg/kg b.w for 30 days showed a significant decrease in fasting blood glucose, hepatic and renal thiobarbituric acid reactive substances and hydroperoxides. The treatment also resulted in a significant increase in reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase in the liver and kidney of diabetic rats. The results clearly suggest that seeds of Momordica charantia treated group may effectively normalize the impaired antioxidant status in streptozotocin induced-diabetes than the glibenclamide treated groups. The extract exerted rapid protective effects against lipid peroxidation by scavenging of free radicals there by reducing the risk of diabetic complications. The effect was more pronounced in MCSEt1 compared to MCSEt2.

  15. Anti-hyperglycemic activity of selenium nanoparticles in streptozotocin-induced diabetic rats

    PubMed Central

    Al-Quraishy, Saleh; Dkhil, Mohamed A; Abdel Moneim, Ahmed Esmat

    2015-01-01

    The study was designed to investigate the anti-hyperglycemic activity of selenium nanoparticles (SeNPs) in streptozotocin-induced diabetic rats. Fifty-five mg/kg of streptozotocin was injected in rats to induce diabetes. Animals either treated with SeNPs alone or with insulin (6 U/kg) showed significantly decreased fasting blood glucose levels after 28 days of treatment. The serum insulin concentration in untreated diabetic animals was also enhanced by SeNPs. The results demonstrated that SeNPs could significantly decrease hepatic and renal function markers, total lipid, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels, and glucose-6-phosphatase activity. At the same time, SeNPs increased malic enzyme, hexokinase and glucose-6-phosphate dehydrogenase activity, liver and kidney glycogen contents, and high-density lipoprotein cholesterol levels. In addition, SeNPs were able to prevent the histological injury in the hepatic and renal tissues of rats. However, insulin injection also exhibited a significant improvement in diabetic animals after 28 days of treatment. This study suggests that SeNPs can alleviate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats, possibly by eliciting insulin-mimetic activity. PMID:26604749

  16. Pharmacological evaluation of “Glyoherb”: A polyherbal formulation on streptozotocin-induced diabetic rats

    PubMed Central

    Thakkar, Nima V.; Patel, Jagruti A.

    2010-01-01

    In the present study, powdered suspension of ‘Glyoherb’- sugar control granules, a polyherbal formulation (manufactured by Dhanvantri Guj. herb., Valasan, Anand, Gujarat, India) was evaluated for its antihyperglycemic, antihyperlipidemic and antioxidant effects against normal and streptozotocin-induced diabetic rats. Type I diabetes was induced when streptozotocin 70 mg/kg was administered as a single i.p. injection. After five days of streptozotocin injection, animals showing glycosuria (fasting blood sugar level >200 mg/dl) were considered as diabetic. Daily oral administration of ‘Glyoherb’ suspension in 200, 400 and 600 mg/kg doses for 28 days produced a dose-dependant decrease in blood glucose levels. It also produced a significant decrease in elevated serum triglyceride, cholesterol, VLDL, LDL, atherogenic index, serum urea, and creatinine and in antioxidant parameters in a dose dependant manner. Results were analyzed using one way ANOVA followed by Tukey's test. No significant changes were noticed in blood glucose, serum lipid levels and kidney parameters in normal rats treated with ‘Glyoherb’ suspension alone. The efficacy of ‘Glyoherb’ suspension as an antihyperglycemic, antihyperlipidemic and antioxidant agent in streptozotocin-induced diabetes was comparable to that of the standard drug Glibenclamide (5 mg/kg). PMID:20431798

  17. The potential benefits and adverse effects of phytic Acid supplement in streptozotocin-induced diabetic rats.

    PubMed

    Omoruyi, F O; Budiaman, A; Eng, Y; Olumese, F E; Hoesel, J L; Ejilemele, A; Okorodudu, A O

    2013-01-01

    In this study, the effect of phytic acid supplement on streptozotocin-induced diabetic rats was investigated. Diabetic rats were fed rodent chow with or without phytic acid supplementation for thirty days. Blood and organ samples were collected for assays. The average food intake was the highest and the body weight gain was the lowest in the group fed phytic acid supplement compared to the diabetic and normal control groups. There was a downward trend in intestinal amylase activity in the group fed phytic acid supplement compared to the other groups. The spike in random blood glucose was the lowest in the same group. We noted reduced serum triglycerides and increased total cholesterol and HDL cholesterol levels in the group fed phytic acid supplement. Serum alkaline phosphatase and alanine amino transferase activities were significantly (P < 0.05) increased by phytic acid supplementation. Systemic IL-1 β level was significantly (P < 0.05) elevated in the diabetic control and supplement treated groups. The liver lipogenic enzyme activities were not significantly altered among the groups. These results suggest that phytic acid supplementation may be beneficial in the management of diabetes mellitus. The observed adverse effect on the liver may be due to the combined effect of streptozotocin-induced diabetes and phytic acid supplementation.

  18. Aortic ER stress in streptozotocin-induced diabetes mellitus in APA hamsters.

    PubMed

    Kurokawa, Masaki; Hideshima, Makoto; Ishii, Yoshiyuki; Kyuwa, Shigeru; Yoshikawa, Yasuhiro

    2009-04-01

    Atherosclerosis is thought to be associated with endoplasmic reticulum (ER) dysfunction and the accumulation of unfolded proteins. In this study, we examined the relationship between atherosclerosis and ER stress and the effect of sodium 4-phenylbutyrate (4-PBA), a kind of chemical chaperone, on atherosclerosis in streptozotocin-induced diabetic APA hamsters. Male, 8-week-old, APA hamsters were injected with streptozotocin (30 mg/kg body weight) to induce diabetes mellitus, and ER stress was evaluated immunohistochemically or by semi-quantitative RT-PCR analysis using ER stress markers such as calreticulin and GPR78. Control hamsters were injected with citrate buffer and were similarly analyzed. In the aorta of control animals, a weak ER stress was detected, and 4-PBA treatment decreased the calreticulin- and GRP78-positive areas and also reduced the mRNA levels of calreticulin and GRP78. On the other hand, strong ER stress was detected at the lesser curvature of the aortic arch of streptozotocin-induced diabetic APA hamsters. However, 4-PBA treatment failed to lessen the ER stress in the aorta and had no effect on improvement of the atherosclerotic lesions. These results may provide an explanation for the complex etiology of atherosclerosis accompanied by diabetes mellitus and various other clinical phenotypes of atherosclerosis.

  19. Effects of dexmedetomidine on renal tissue after lower limb ischemia reperfusion injury in streptozotocin induced diabetic rats

    PubMed Central

    Erbatur, Meral Erdal; Sezen, Şaban Cem; Bayraktar, Aslıhan Cavunt; Arslan, Mustafa; Kavutçu, Mustafa; Aydın, Muhammed Enes

    2017-01-01

    ABSTRACT Aim: The aim of this study was to investigate whether dexmedetomidine – administered before ischemia – has protective effects against lower extremity ischemia reperfusion injury that induced by clamping and subsequent declamping of infra-renal abdominal aorta in streptozotocin-induced diabetic rats. Material and Methods: After obtaining ethical committee approval, four study groups each containing six rats were created (Control (Group C), diabetes-control (Group DM-C), diabetes I/R (Group DM-I/R), and diabetes-I/R-dexmedetomidine (Group DM-I/R-D). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DM-C. In Group DM-I/R, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DM-I/R-D, 100 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia period. At the end of reperfusion, period biochemical and histopathological evaluation of renal tissue specimen were performed. Results: Thiobarbituric acid reactive substance (TBARS), Superoxide dismutase (SOD), Nitric oxide synthase (NOS), Catalase (CAT) and Glutathion S transferase (GST) levels were found significantly higher in Group DM-I/R when compared with Group C and Group DM-C. In the dexmedetomidine-treated group, TBARS, NOS, CAT, and GST levels were significantly lower than those measured in the Group D-I/R. In histopathological evaluation, glomerular vacuolization (GV), tubular dilatation (TD), vascular vacuolization and hypertrophy (VVH), tubular cell degeneration and necrosis (TCDN), tubular hyaline cylinder (THC), leucocyte infiltration (LI), and tubular cell spillage (TCS) in Group DM-I/R were significantly increased when compared with the control group

  20. Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro

    PubMed Central

    Shen, Xin; Zhou, Nan; Mi, Le; Hu, Zishuo; Wang, Libin; Liu, Xueying; Zhang, Shengyong

    2017-01-01

    The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph). In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6) myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05) reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD–POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of type 2 diabetes (T2D) rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes. PMID:28223777

  1. Antihyperlipidemic effect of fisetin, a bioflavonoid of strawberries, studied in streptozotocin-induced diabetic rats.

    PubMed

    Prasath, Gopalan Sriram; Subramanian, Sorimuthu Pillai

    2014-10-01

    Chronic hyperglycemia in diabetes is associated with profound changes in lipid and lipoprotein metabolism, with resultant alterations in particle distribution within lipoprotein classes. In the present study, an attempt has been made to explore the antihyperlipidemic effect of fisetin in streptozotocin-induced experimental diabetes in rats. Upon fisetin treatment to diabetic rats, the levels of blood glucose were significantly reduced with an improvement in plasma insulin. The increased levels of lipid contents in serum, hepatic, and renal tissues observed in diabetic rats were normalized upon fisetin administration. Also, the decreased levels of high-density lipoprotein cholesterol, and increased levels of low-density lipoprotein (LDL) and very LDL (VLDL) cholesterol in serum of diabetic rats were normalized. Oil Red O staining established a large number of intracellular lipid droplets accumulation in the diabetic rats. Fisetin treatment exacerbated the degree of lipid accumulation. The results of the present study exemplify the antihyperlipidemic property of the fisetin.

  2. Polysaccharides isolated from Phellinus gilvus enhances dermal wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Bae, Jae-Sung; Jang, Kwang-Ho; Jin, Hee-Kyung

    2005-06-01

    Dermal wound healing is a complex process that involved inflammation leading to re-epithelialization, granulation tissue, and tissue remodeling. Previous studies from our laboratory have shown that polysaccharides isolated from fungus, Phellinus gilvus (PG) have various anti-inflammatory activities. In present study, we have assessed the effect of polysaccharides from PG on the dermal wound healing of polysaccharides from PG in streptozotocin-induced diabetic rat model. Six of 6-mm circular wounds were created with biopsy punch on the 4th day after induction of diabetes. After 24 hours, each test substance was applied to the wound twice a day for next 5 days. Circular wounds treated with PG showed significantly reduced wound contraction and complete reepithelialization, as compared to wounds of non-treated (p<0.05). These results show that polysaccharides isolated from PG enhanced wound repair in diabetic impaired healing, and could be developed as a wound healing agent in such clinical settings.

  3. Antihyperglycemic activity of Caralluma tuberculata in streptozotocin-induced diabetic rats.

    PubMed

    Abdel-Sattar, Essam A; Abdallah, Hossam M; Khedr, Alaa; Abdel-Naim, Ashraf B; Shehata, Ibrahim A

    2013-09-01

    The current study aimed at evaluating the potential and mechanisms of the antidiabetic activity of the methanolic extract (ME) of Caralluma tuberculata as well as its chloroform (CF), n-butanol (BF) and the remaining water fractions (RFs) in streptozotocin-induced diabetic rats. The antidiabetic activity was evaluated through assessing fasting blood glucose (FBG), insulin levels, oral glucose tolerance test (OGTT), glucose utilization by isolated rat psoas muscle, gut glucose absorption and G-6-Pase activity in isolated rat liver microsomes. Both ME and RF showed the highest potency, where ME had superior activity. The mechanism underlying the observed antihyperglycemic activity of ME could be attributed, at least in part, to enhanced skeletal muscle utilization of glucose, inhibition of hepatic gluconeogenesis and stimulation of insulin secretion. ME was standardized through LC-MS analysis for its major pregnanes.

  4. Hypoglycemic effect of syringin from Eleutherococcus senticosus in streptozotocin-induced diabetic rats.

    PubMed

    Niu, Ho-Shan; Liu, I-Min; Cheng, Juei-Tang; Lin, Che-Ling; Hsu, Feng-Lin

    2008-02-01

    Eleutherococcus senticosus (Araliaceae ) is a very powerful adaptogenic agent. In the present study, the effects of syringin, an active principle of this herb, on plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats) were investigated. Thirty minutes after syringin was intravenously injected into fasting STZ-diabetic rats, plasma glucose levels dose-dependently decreased. In normal rats, syringin at the effective dose (1.0 mg/kg) significantly attenuated the increase in plasma glucose caused by an intravenous glucose challenge. Syringin dose-dependently (0.01 to 10.0 micromol/L) stimulated glucose uptake in soleus muscle isolated from STZ-diabetic rats. Syringin treatment of hepatocytes isolated from STZ-diabetic rats enhanced glycogen synthesis . The ability of syringin to enhance glucose utilization and lower plasma glucose level in rats suffering from insulin deficiency suggest that this chemical may be useful in the treatment of human diabetes.

  5. Effect of All-Trans Retinoic Acid on the Pancreas of Streptozotocin-Induced Diabetic Rat.

    PubMed

    Eltony, Sohair A; Elmottaleb, Nashwa A; Gomaa, Asmaa M; Anwar, Mamdouh M; El-Metwally, Tarek H

    2016-03-01

    All-trans Retinoic acid (atRA) is instructive for the development of endocrine pancreas and is an integral component of β-cell induction protocols. We showed that atRA induces glucose-responsive endocrine transdifferentiation of pleomorphic pancreatic ductal adenocarcinoma cells in vitro. This study aimed to detect the role of atRA in improving the histological changes of the pancreas in diabetic rats. Forty young male Wistar rats were used and divided into three groups. Group I: normal vehicle control (N = 5). Group II: streptozotocin-induced diabetic rats (N = 20) were followed up at 0.0, 1, 2, and 4 weeks. Group III: streptozotocin-induced diabetic rats (N = 15) treated with atRA (2.5 mg/kg/day), were followed up at 1, 2, and 4 weeks. Specimens from the pancreas were processed for light, electron microscopy and pancreatic insulin mRNA expression. Blood samples were assayed for the levels of glucose, insulin, and total peroxides. In the atRA-treated group, the number of the islets and the islet area significantly increased. Strong insulin-immunoreactive endocrine-like cells were observed nearby the pancreatic acini and the interlobular ducts. Interestingly, insulin-positive cells seemed to arise from pancreatic acinar and ductal epithelium. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. Pancreatic insulin mRNA and blood indices were almost normalized. AtRA improved the histological changes of the pancreas and the blood indices in diabetic rats.

  6. Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats.

    PubMed

    Kim, Sok Ho; Kwon, Jung Kee; Kwon, Young Bae

    2012-06-01

    Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain. For this reason, the present study was aimed to address the induction of pain modalities and spinal glial expression after streptozotocin injection as compared with that of zymosan inflammation in the rat. Evaluation of pain behavior by either thermal or mechanical stimuli was performed at 3 weeks or 5 hours after either intravenous streptozotocin or zymosan. Degrees of pain were divided into 4 groups: severe, moderate, mild, and non-pain induction. On the mechanical allodynia test, zymosan evoked predominantly a severe type of pain, whereas streptozotocin induced a weak degree of pain (severe+moderate: 57.1%). Although zymosan did not evoke cold allodynia, streptozotocin evoked stronger pain behavior, compared with zymosan (severe+moderate: 50.0%). On the other hand, the high incidence of thermal hyperalgesia (severe+moderate: 90.0%) and mechanical hyperalgesia (severe+moderate: 85.7%) by streptozotocin was observed, as similar to that of zymosan. In the spinal cord, the increase of microglia and astrocyte was evident by streptozotocin, only microglia was activated by zymosan. Therefore, it is recommended that the selection of mechanical and thermal hyperalgesia is suitable for the evaluation of streptozotocin induced diabetic peripheral neuropathy. Moreover, spinal glial activation may be considered an important factor.

  7. Laser irradiation affects enzymatic antioxidant system of streptozotocin-induced diabetic rats.

    PubMed

    Ibuki, Flavia Kazue; Simões, Alyne; Nicolau, José; Nogueira, Fernando Neves

    2013-05-01

    The aim of the present study was to analyze the effect of low-power laser irradiation in the antioxidant enzymatic system of submandibular (SMG) and parotid (PG) salivary glands of streptozotocin-induced diabetic rats. The animals were randomly divided into six groups: three diabetic groups (D0, D5, and D20) and three non-diabetic groups (C0, C5, and C20), according to laser dose received (0, 5, and 20 J/cm(2), respectively). Areas of approximately 1 cm(2) were demarcated in the salivary glands (each parotid and both submandibular glands) and after irradiated according to Simões et.al. (Lasers Med Sci 24:202-208, 2009). A diode laser (660 nm/100 mW) was used, with laser beam spot of 0.0177 cm(2). The group treated with 5 J/cm(2) laser dose was subjected to irradiation for 1 min and 4 s (total irradiation time) and the group treated with 20 J/cm(2) laser dose was subjected to irradiation for 4 min and 16 s. Twenty-four hours after irradiation the animals were euthanized and the salivary glands were removed for biochemical analysis. The total antioxidant values (TA), the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase enzymes were determined. SOD and CAT activities, as well as TA were higher in SMG of irradiated diabetic rats. However, in SMG of non-diabetic rats, laser irradiation decreased TA values and led to an increase in the CAT activity. In addition, there was a decrease in the activity of CAT in PG of diabetic and non-diabetic animals after laser irradiation. According to the results of the present study, low-power laser irradiation can affect the enzymatic antioxidant system of salivary glands of streptozotocin-induced diabetic rats.

  8. Antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rodents

    PubMed Central

    2014-01-01

    Background Painful neuropathy is the most common and debilitating complication of diabetes and results in hyperalgesia and allodynia. Hyperglycemia clearly plays a key role in the development and progression of diabetic neuropathy. Current therapeutic approaches are only partially successful and they are only thought to reduce the pain associated with peripheral neuropathy. Some natural products offer combined antioxidant, anti-inflammatory and antinociceptive properties that may help to treat in a more integrative manner this condition. In this regard, the purpose of this study was to investigate the antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rats and mice without glucose control as well as the possible mechanism of action involved in this effect. Methods Rats and mice were injected with 50 or 200 mg/kg streptozotocin, respectively, to produce hyperglycemia. The formalin test and von Frey filaments were used to assess the nociceptive activity. Rota-rod was utilized to measure motor activity and malondialdehyde assay to determine anti-oxidative properties. Results After 3 weeks of diabetes induction, chemical hyperalgesia was observed in streptozotocin-injected rats. Oral acute administration of 7-hydroxy-3,4-dihydrocadalin (0.3–30 mg/kg) decreased in a dose-dependent manner formalin-evoked hyperalgesia in diabetic rats. In addition, methiothepin (non-selective 5-HT receptor antagonist, 1 mg/kg, i.p.) and ODQ (guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (opioid receptor antagonist, 1 mg/kg, s.c.), prevented 7-hydroxy-3,4-dihydrocadalin-induced antihyperalgesic effect. The anti-hyperalgesic effect of 7-hydroxy-3,4-dihydrocadalin was similar to that produced by pregabalin (10 mg/kg, p.o.). Furthermore, oral acute administration of 7-hydroxy-3,4-dihydrocadalin (30 mg/kg) reduced streptozotocin-induced changes in malondialdehyde concentration from plasma samples. Unlike pregabalin, 7-hydroxy-3

  9. Antidiabetic effects of dendropanoxide from leaves of Dendropanax morbifera Leveille in normal and streptozotocin-induced diabetic rats.

    PubMed

    Moon, Hyung-In

    2011-08-01

    The present study evaluated the antidiabetic effect of Dendropanoxide (DP) from Dendropanax morbifera Leveille in normal and streptozotocin-induced diabetic rats. DP in the streptozotocin-induced diabetic rats showed significant hypoglycemic activity for 14 days significantly decreased the serum glucose, total cholesterol, triglycerides, urea, uric acid, creatinine, aspartate amino transferase (AST) and alanine amino transferase (ALT) while it increased the serum insulin in diabetic rats but not in normal rats (p < 0.05; at doses of 30, 60 and 100 mg/kg for 14 days). A comparison was made between the action of DP and glibenclamide (600 μg/kg), a known antidiabetic drug. The antidiabetic effect of the DP was more effective than that observed with glibenclamide.

  10. Role of Nitric Oxide in the Pathogenesis of Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Choi, Ki Chul; Lee, Seong Cheol; Kim, Soo Wan; Kim, Nam Ho; Lee, Jong-Un; Kang, Young Joon

    1999-01-01

    Objectives Several reports suggest that enhanced generation or actions of nitric oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration and hyperperfusion that occurs in early diabetes. However, the precise role of altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The present study was aimed at investigating the role of nitric oxide in the pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin-induced diabetic rats. Methods To evaluate the role of NO in diabetic hyperfiltration, we measured plasma and urine concentrations of NO2−/NO3−, stable metabolic products of NO and protein expressions of three isoforms of nitric oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also investigated renal hemodynamic changes, such as glomerular filtration rate (GFR) and renal plasma flow (RPF), in responses to acute and chronic administration of NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and control rats. Results Diabetic rats exhibited significantly elevated plasma and urinary NO2−/NO3− levels at 28 days after streptozotocin injection, and total excretion of NO2−/NO3− was approximately five-fold higher in diabetic rats than controls. Insulin and L-NAME treatment prevented the increases in plasma and urinary NO2−/NO3− concentrations in diabetic rats, respectively. The three isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex, whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were significantly elevated in diabetic rats, and acute and chronic inhibition of NO synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR and RPF) in diabetic rats, respectively. Conclusions NO synthesis was increased due to enhanced NOS expression in diabetic rats, and chronic NO blockade attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In addition, diabetic rats

  11. Anti-Oxidative Effect of Cassia auriculata on Streptozotocin Induced Diabetic Rats

    PubMed Central

    Ashok, V.

    2010-01-01

    The anti oxidative effect of administration of 100 mg/kg bw and 200 mg/kg bw of the flower powder of Cassia auriculata (CFP) for 45 days to normoglycemic and diabetic rats (streptozotocin induced) was studied. Anti oxidative effect was not observed in normoglycemic rats in the experiment. There was significant (P > 0.05) increase in the level of Thio Barbituric Acid Reactive Substances (TBARS), hydroperoxide and conjugated dienes and significant (P > 0.05) decrease in the catalase, superoxide dismutase and glutathione peroxidase activities and in the level of ascorbic acid, vitamin E and reduced glutathione in diabetic rats. The flower powder of Cassia auriculata significantly (P > 0.05) decreased the TBARS, hydroperoxide and conjugated dienes and increased the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and non enzymic anti oxidants (ascorbic acid, vitamin E and reduced glutathione). The antioxidatve effect of 200 mg/kg bw CFP was significantly (P > 0.05) better than 100 mg/kg bw CFP and the reference drugs (tolbutamide and metformin). The mode of action of CFP remains to be elicited. PMID:21966119

  12. Free Radical Scavenging Activity of Calotropis gigantea on Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Rathod, N. R.; Raghuveer, I.; Chitme, H. R.; Chandra, R.

    2009-01-01

    Swarnabhasma, an Ayurvedic preparation containing Calotropis gigantea R. Br. (Asclepiadaceae) is extensively used by Ayurvedic physicians for treatment of diabetes mellitus, bronchial asthma, rheumatoid arthritis and nervous disorders. In the present study, we report the effect of chloroform extracts of Calotropis gigantea leaf and flower on free radical scavenging activity, and lipid profile in streptozotozin-induced diabetic rats. The lipid peroxidation, superoxide dismutase, and catalase were measured in liver homogenate and serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, lipid profile were measured in blood serum. Administration of single dose of streptozotozin (55 mg/kg, i.p.) caused significant increases in lipid peroxidation, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, cholesterol and triglyceride levels, while superoxide dismutase and catalase levels were significantly decreased. Further, administration of chloroform extracts of Calotropis gigantea leaf and flower to streptozotocin-induced diabetes rats at a dose of 10, 20 and 50 mg/kg orally for 27 d lead to a significant decrease in lipid peroxidation, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, cholesterol and triglyceride levels. Consequently, superoxide dismutase and catalase levels were significantly increased. Glibenclamide was used as a positive control (10 mg/kg). It was observed that the effect of chloroform extracts of Calotropis gigantea on alkaline phosphatase, cholesterol, superoxide dismutase, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, levels are comparable to that of those produced by the positive control. PMID:20376213

  13. Evaluation of Antihyperglycemic Activity of Citrus limetta Fruit Peel in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    KunduSen, Sriparna; Haldar, Pallab K.; Gupta, Malaya; Mazumder, Upal K.; Saha, Prerona; Bala, Asis; Bhattacharya, Sanjib; Kar, Biswakanth

    2011-01-01

    The present paper aims to evaluate antihyperglycemic activity of methanol extract of Citrus limetta fruit peel (MECL) in streptozotocin-induced (STZ; 65 mg/kg b.w.) diabetic rats. Three days after STZ induction, diabetic rats received MECL orally at 200 and 400 mg kg−1 body weight daily for 15 days. Glibenclamide (0.5 mg kg−1 p. o.) was used as reference drug. Blood glucose levels were measured on 0th, 4th, 8th, and 15th days of study. Serum biochemical parameters namely, SGOT, SGPT and ALP were estimated. The TBARS and GSH levels of pancreas, kidney, and liver were determined. MECL significantly (P < 0.001) and dose dependently normalized blood glucose levels and serum biochemical parameters, decreased lipid peroxidation, and recovered GSH as compared to those of STZ control. The present paper infers that in STZ-induced diabetic Wistar rats, C. limetta fruit peel demonstrated a potential antihyperglycemic effect which may be attributed to its antioxidant property. PMID:22363893

  14. Evaluation of hypoglycemic activity of the leaves of Malva parviflora in streptozotocin-induced diabetic rats.

    PubMed

    Perez Gutierrez, Rosa Martha

    2012-04-01

    Malva parviflora (MP), known in Mexico by the name of "quesitos" or "malva", is popular due to its culinary and medicinal properties. Diabetic rats were treated with the hexane, chloroform and methanol extracts of the M. parviflora leaves for 28 days and a set of biochemical parameters were studied including: glucose level, total cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. We also looked into liver function by determining glucose-6-phosphatase, glucokinase and hexokinase activities, and the effect of the extracts on insulin level and protein glycation. As a result we found that with the hexane extract the blood glucose level, serum biochemical parameters, hepatic enzymes, thiobarbituric acid reactive substances, glycosylated hemoglobin, advanced glycation end products, and insulin level were restored in streptozotocin induced diabetic rats to nearly normal levels. We conclude that the hexane extract of M. parviflora leaves can efficiently inhibit insulin resistance, lipid abnormalities and oxidative stress, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in diabetes pathogenesis.

  15. Perfluorononanoic acid disturbed the metabolism of lipid in the liver of streptozotocin-induced diabetic rats.

    PubMed

    Fang, Xuemei; Gao, Guizhen; Zhang, Xingtao; Wang, Haichao

    2015-01-01

    Most studies on the liver toxicity of perfluorinated compounds (PFCs) are focused on healthy individuals, whereas the effects of PFCs on individuals with diabetes mellitus have not been fully characterized. This study aimed to investigate the acute exposure of perfluorononanoic acid (PFNA) on the metabolism of lipid in the liver of streptozotocin-induced diabetic rats. Male diabetic rats were orally dosed by gavage for 7 days with 0, 0.2, 1 and 5 mg/kg/day PFNA. The contents of lipid, the activities of enzyme, the expressions of protein in the liver and the serum parameters were detected. The results indicate that dose-dependent accumulation of triglyceride and total cholesterol occurred in the livers of diabetic rats after PFNA treatment. PFNA increased the activities of lipid synthetase, fatty acid synthease, glucose-6-phosphate dehydrogenase and decreased the activity of lipolytic enzyme, hepatic lipase, in the liver of diabetic rats. The changes of the isocitrate dehydrogenase, malicenzyme and lipoprotein lipase were not obvious. The expressions of protein related to lipid homeostasis, liver X receptor α and apolipoprotein E, were decreased after PFNA administration. Exposure to PFNA also increased the activity of serum alanine aminotransferase in diabetic rats. In conclusion, this study discloses that exposure to PFNA impacts on enzymes and proteins related to liver lipid metabolism and lead to obvious accumulation of lipid in the liver of diabetic rats, which may be responsible for hepatotoxicity of this compound in individuals with diabetes mellitus.

  16. Effect of Agaricus blazei Murill on the Pulmonary Tissue of Animals with Streptozotocin-Induced Diabetes

    PubMed Central

    Di Naso, Fábio Cangeri; de Mello, Rodrigo Noronha; Bona, Sílvia; Dias, Alexandre Simões; Porawski, Marilene; Ferraz, Alexandre de Barros Falcão; Richter, Marc François; Marroni, Norma Possa

    2010-01-01

    The present study was designed to evaluate the oxidative stress as well as the therapeutic effect of Agaricus blazei Muril (A. Blazei) in rats with streptozotocin-induced diabetes. We used 25 Wistar rats, and DM was induced by injecting streptozotocin (70 mg/Kg i.p.). Agaricus blazei Muril was administered daily starting 40 days after disease onset. A. Blazei was tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipoperoxidation (LPO), and superoxide dismutase (SOD), catalase, and glutathione peroxidase activities were measured in the pulmonary tissue, as well as the presence of inducible nitric oxide synthase (iNOS), through immunohistochemistry. An anatomopathologic study was also performed. Phytochemical screening of A. Blazei detected the presence of alkaloids and saponins. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hipoxanthine/xanthine oxidase assays. Pulmonary LPO increased in diabetic animals (0.43 ± 0.09; P < .001) as compared to the control group (0.18 ± 0.02), followed by a reduction in the A. Blazei-treated group (0.33 ± 0.04; P < .05). iNOS was found increased in the lung in diabetic rats and reduced in the A. Blazei-treated group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. The A. Blazei treatment effectively reduced the oxidative stress and contributed to tissue recovery. PMID:20585363

  17. Antihyperglycemic, antihyperlipidemic and antioxidant activities of polysaccharides from Catathelasma ventricosum in streptozotocin-induced diabetic mice.

    PubMed

    Liu, Yuntao; Sun, Jun; Rao, Shengqi; Su, Yujie; Yang, Yanjun

    2013-07-01

    It is the first time to extract polysaccharides (CVPs) from Catathelasma ventricosum. The antihyperglycemic and antioxidant activity of CVPs in streptozotocin-induced diabetic mice were examined. Compared with untreated diabetic mice, the administration of CVPs for 30 days caused a significant decrease in the concentrations of blood glucose, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C) and maleic dialdehyde (MDA), and a significant increase in the concentrations of high density lipoprotein-cholesterol (HDL-C) and the activities of antioxidant enzymes. Specially, when normal mice were treated with CVPs, all detection indexes and pathologic morphologies of liver, kidney and pancreas are similar to untreated normal mice, which indicated CVPs are safe for normal mice. In addition, the average molecular weight of CVPs was estimated to be from 3.7 × 10(3) to 1.7 × 10(7)Da and they were mainly composed of glucose (93.5%) with the conformation of α-d-Glucopyranose.

  18. Effect of Agaricus blazei Murill on the pulmonary tissue of animals with streptozotocin-induced diabetes.

    PubMed

    Di Naso, Fábio Cangeri; de Mello, Rodrigo Noronha; Bona, Sílvia; Dias, Alexandre Simões; Porawski, Marilene; Ferraz, Alexandre de Barros Falcão; Richter, Marc François; Marroni, Norma Possa

    2010-01-01

    The present study was designed to evaluate the oxidative stress as well as the therapeutic effect of Agaricus blazei Muril (A. Blazei) in rats with streptozotocin-induced diabetes. We used 25 Wistar rats, and DM was induced by injecting streptozotocin (70 mg/Kg i.p.). Agaricus blazei Muril was administered daily starting 40 days after disease onset. A. Blazei was tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipoperoxidation (LPO), and superoxide dismutase (SOD), catalase, and glutathione peroxidase activities were measured in the pulmonary tissue, as well as the presence of inducible nitric oxide synthase (iNOS), through immunohistochemistry. An anatomopathologic study was also performed. Phytochemical screening of A. Blazei detected the presence of alkaloids and saponins. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hipoxanthine/xanthine oxidase assays. Pulmonary LPO increased in diabetic animals (0.43 +/- 0.09; P < .001) as compared to the control group (0.18 +/- 0.02), followed by a reduction in the A. Blazei-treated group (0.33 +/- 0.04; P < .05). iNOS was found increased in the lung in diabetic rats and reduced in the A. Blazei-treated group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. The A. Blazei treatment effectively reduced the oxidative stress and contributed to tissue recovery.

  19. Antihyperglycemic and antioxidant activity of Clitorea ternatea Linn. on streptozotocin-induced diabetic rats

    PubMed Central

    Talpate, Karuna A.; Bhosale, Uma A.; Zambare, Mandar R.; Somani, Rahul

    2013-01-01

    Ethanol extract of Clitorea ternatea Linn. (EECT) was evaluated for its antihyperglycemic and antioxidative activity in normal and streptozotocin-induced diabetic rats. Antihyperglycemic activity of EECT was studied in normal fasted and glucose fed hyperglycemic and epinephrine induced hyperglycemic rats by estimating fasting serum glucose (FSG) by glucose oxidisae or peroxidase enzymatic method. Antioxidant activity of EECT was studied by assaying lipid peroxide/Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), total nitric oxide, catalase (CAT) and glutathione levels in diabetic rats. The EECT (200 and 400 mg/kg) showed significant antihyperglycemic activity by decreasing FSG in all hyperglycemic models except epinephrine induced hyperglycemic rats; in which improvement in FSG was observed only with EECT in 400 mg/kg dose, whereas significant decrease in TBARS (P < 0.001), nitric oxide (P < 0.001) and significant increase in SOD (P < 0.001), CAT (P < 0.01) and reduced glutathione levels (P < 0.001) was observed in animals treated with EECT (200 and 400 mg/kg) compared to diabetic control group. The results indicated that EECT has remedial effects on hyperglycemia and oxidative stress in diabetic rats. PMID:24696583

  20. Rooibos tea (Aspalathus linearis) partially prevents oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Ulicná, O; Vancová, O; Bozek, P; Cársky, J; Sebeková, K; Boor, P; Nakano, M; Greksák, M

    2006-01-01

    The aim of this study was to investigate the effects of rooibos tea as a natural source of a wide scale of antioxidants on the prevention and treatment of oxidative stress in streptozotocin-induced diabetic rats. Expected significant changes of biochemical parameters characteristic for experimental diabetic state were found in plasma and tissues eight weeks after single dose streptozotocin application. Administration of aqueous and alkaline extracts of rooibos tea (or N-acetyl-L-cysteine for comparison) to diabetic rats did not affect markers of the diabetic status (glucose, glycated hemoglobin and fructosamine). Besides the parameters characterizing hepatotoxic effect of streptozotocin, rooibos tea significantly lowered advanced glycation end-products (AGEs) and malondialdehyde (MDA) in the plasma and in different tissues of diabetic rats, particularly MDA concentration in the lens. From these results we can conclude that antioxidant compounds in rooibos tea partially prevent oxidative stress and they are effective in both hydrophobic and hydrophilic biological systems. Therefore, rooibos tea as a commonly used beverage can be recommended as an excellent adjuvant support for the prevention and therapy of diabetic vascular complications, particularly for protecting ocular membrane systems against their peroxidation by reactive oxygen species.

  1. Increased Inner Ear Susceptibility to Noise Injury in Mice With Streptozotocin-Induced Diabetes

    PubMed Central

    Fujita, Takeshi; Yamashita, Daisuke; Katsunuma, Sayaka; Hasegawa, Shingo; Tanimoto, Hitoshi; Nibu, Ken-ichi

    2012-01-01

    We aimed to investigate the pathophysiology of diabetes-associated hearing impairment in type 1 diabetes using mice with streptozotocin-induced diabetes (C57BL/6J; male). Hearing function was evaluated 1, 3, and 5 months after induction of diabetes (five diabetic and five control animals per time point) using auditory-evoked brain stem responses (ABRs). Mice (four diabetic and four control) were exposed to loud noise (105 dB) 5 months after induction of diabetes. ABRs were measured before and after noise exposure. Cochlear blood flows were measured by laser-Doppler flowmeter. Spiral ganglion cells (SGCs) were counted. Vessel endothelial cells were observed by CD31 immunostaining. Chronologic changes in the ABR threshold shift were not significantly different between the diabetic and control groups. However, vessel walls in the modiolus of the cochleae were significantly thicker in the diabetic group than the control group. Additionally, recovery from noise-induced injury was significantly impaired in diabetic mice. Reduced cochlea blood flows and SGC loss were observed in diabetic mice cochleae after noise exposure. Our data suggest that diabetic cochleae are more susceptible than controls to loud noise exposure, and decreased cochlear blood flow due to sclerosis of the vessels and consequent loss of SGCs are possible mechanisms of hearing impairment in diabetic patients. PMID:22851574

  2. Plasminogen Activator Inhibitor-1 Is Involved in Streptozotocin-Induced Bone Loss in Female Mice

    PubMed Central

    Tamura, Yukinori; Kawao, Naoyuki; Okada, Kiyotaka; Yano, Masato; Okumoto, Katsumi; Matsuo, Osamu; Kaji, Hiroshi

    2013-01-01

    In diabetic patients, the risk of fracture is high because of impaired bone formation. However, the details of the mechanisms in the development of diabetic osteoporosis remain unclear. In the current study, we investigated the role of plasminogen activator inhibitor (PAI)-1 in the pathogenesis of type 1 diabetic osteoporosis by using PAI-1–deficient mice. Quantitative computed tomography analysis showed that PAI-1 deficiency protected against streptozotocin-induced bone loss in female mice but not in male mice. PAI-1 deficiency blunted the changes in the levels of Runx2, osterix, and alkaline phosphatase in tibia as well as serum osteocalcin levels suppressed by the diabetic state in female mice only. Furthermore, the osteoclast levels in tibia, suppressed in diabetes, were also blunted by PAI-1 deficiency in female mice. Streptozotocin markedly elevated the levels of PAI-1 mRNA in liver in female mice only. In vitro study demonstrated that treatment with active PAI-1 suppressed the levels of osteogenic genes and mineralization in primary osteoblasts from female mouse calvaria. In conclusion, the current study indicates that PAI-1 is involved in the pathogenesis of type 1 diabetic osteoporosis in females. The expression of PAI-1 in the liver and the sensitivity of bone cells to PAI-1 may be an underlying mechanism. PMID:23715621

  3. Capparis spinosa L. aqueous extract evokes antidiabetic effect in streptozotocin-induced diabetic mice

    PubMed Central

    Eddouks, Mohamed; Lemhadri, Ahmed; Hebi, Morad; EL Hidani, Ahmed; Zeggwagh, Naoufel Ali; EL Bouhali, Bachir; Hajji, Lhoussaine; Burcelin, Remy

    2017-01-01

    Objective: As the aqueous extract of Capparis spinosa (CS) possess antidiabetic effect, he present study aims to reveal the possible mechanism of action of CS in diabetic mice. Materials and Methods: Both single and repeated oral administrations of aqueous extract of CS were performed in multi-low dose streptozotocin-induced (MLDS) diabetic mice. Euglycemic hyperinsulinemic clamp was used in association with the endogenous glucose production (perfusion rate of 3-3H glucose) to evaluate the effect of CS aqueous extract on insulin sensitivity. Results: Our study showed that aqueous extract of CS possess a potent hypoglycaemic activity in MLDS diabetic mice. Furthermore, the analysis perfusion of 3-3H glucose demonstrated the parallel decrease of basal endogenous glucose production (EGP) with the hypoglycaemic activity. EGP was lower in CS-Treated group when compared to the control group (p<0.001). The euglycemic hyperinsulinemic clamp technique demonstrated that CS treatment improves insulin sensitivity in peripheral tissues. Conclusion: We conclude that the antihyperglycemic effet CS is probably due to the inhibition of basal endogenous glucose production and the improvement of insulin sensitivity in MLDS diabetic mice. PMID:28348974

  4. Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice.

    PubMed

    Guo, Chuanlong; Li, Mengshuang; Qi, Xia; Lin, Guiming; Cui, Fenghua; Li, Fengjie; Wu, Xianggen

    2016-07-11

    Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy.

  5. Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats.

    PubMed

    Bădescu, S V; Tătaru, C P; Kobylinska, L; Georgescu, E L; Zahiu, D M; Zăgrean, A M; Zăgrean, L

    2016-01-01

    Diabetes mellitus modifies the expression of adenosine receptors in the brain. Caffeine acts as an antagonist of A1 and A2A adenosine receptors and was shown to have a dose-dependent biphasic effect on locomotion in mice. The present study investigated the link between diabetes and locomotor activity in an animal model of streptozotocin-induced diabetes, and the effects of a low-medium dose of caffeine in this relation. The locomotor activity was investigated by using Open Field Test at 6 weeks after diabetes induction and after 2 more weeks of chronic caffeine administration. Diabetes decreased locomotor activity (total distance moved and mobility time). Chronic caffeine exposure impaired the locomotor activity in control rats, but not in diabetic rats. Our data suggested that the medium doses of caffeine might block the A2A receptors, shown to have an increased density in the brain of diabetic rats, and improve or at least maintain the locomotor activity, offering a neuroprotective support in diabetic rats. Abbreviations: STZ = streptozotocin, OFT = Open Field Test.

  6. Cooked common beans (Phaseolus vulgaris L.) modulate renal genes in streptozotocin-induced diabetic rats.

    PubMed

    Lomas-Soria, Consuelo; Pérez-Ramírez, Iza F; Caballero-Pérez, Juan; Guevara-Gonzalez, Ramón G; Guevara-Olvera, Lorenzo; Loarca-Piña, Guadalupe; Guzman-Maldonado, Horacio S; Reynoso-Camacho, Rosalía

    2015-07-01

    Food consumption with different bioactive compounds could reduce the risk of diabetic complications. This study was designed to evaluate the effect of cooked common beans on differentially expressed genes in whole kidney homogenates of streptozotocin-induced diabetic rats. After 4weeks of treatment with a cooked bean supplemented (10%) diet, animals fed with Flor de Mayo bean (FMB) exerted the greatest protective effect, since they presented the lowest blood glucose levels, consistent with an increase in blood insulin levels, a decrease in urine albumin and urea levels and an increase in creatinine clearance (P≤.05). Regarding the gene expression of kidneys evaluated using expressed sequence tag, consumption of cooked beans improved the expression of Glu1, Cps1, Ipmk, Cacna1c, Camk1, Pdhb, Ptbp3 and Pim1, which are related to the elimination of ammonium groups, the regulation of inflammatory and oxidative response, as well as cell signaling and apoptosis. In addition, the beneficial effects observed were not related to their polyphenolic and saponin profile, suggesting the activity of other bioactive compounds or the synergistic interaction of these compounds. These results suggest that the consumption of cooked common beans (FMB) might be used as an alternative for the regulation of genes related to renal alterations.

  7. Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.

    PubMed

    Valcheva-Kuzmanova, S; Kuzmanov, K; Tancheva, S; Belcheva, A

    2007-03-01

    Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications.

  8. Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats.

    PubMed

    Nagareddy, Prabhakara Reddy; Vasudevan, Harish; McNeill, John H

    2005-05-01

    Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.

  9. Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice

    PubMed Central

    Guo, Chuanlong; Li, Mengshuang; Qi, Xia; Lin, Guiming; Cui, Fenghua; Li, Fengjie; Wu, Xianggen

    2016-01-01

    Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy. PMID:27405815

  10. The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats.

    PubMed

    Wang, Te; Cai, Leyi; Wang, Yangyang; Wang, Qingqing; Lu, Di; Chen, Hua; Ying, Xiaozhou

    2017-03-05

    Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkg(-1)day(-1) of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkg(-1)day(-1) of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkg(-1)day(-1) orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkg(-1)day(-1) orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes.

  11. Profertility and antidiabetic properties of Gynura procumbens on streptozotocin induced male rats

    NASA Astrophysics Data System (ADS)

    Khaidatul Akmar, K.; Mahanem, M. N.

    2016-11-01

    Gynura procumbens (GP) is an herbal plant that is used for treating diseases such as diabetes mellitus, cardiovascular and also fertility. The objective of this study was to determine the anti-diabetic and pro-fertility effect of GP on streptozotocin induced male rats within 14 days. A total of 42 male rats were randomly assigned into six groups; normal, negative, and positive control, and three treated groups of different dosages of GP; 150 mg/kg, 300 mg/kg and 450 mg/kg. The treated groups were given aqueous extract GP via oral gavage for 14 consecutive days. The fasting blood glucose (FBG) level in all treated groups showed significant decreased compared to negative and positive group after 14 days treatment. Sperm quality parameters in GP treated group (450 mg/kg) showed significant increase when compared to negative and positive group. It was observed that the histology of testes in the treated group (450 mg/kg) produced a significant result whereby the germinal cell layer shown an arranged order of cells compared to the negative and positive control groups. It appeared that aqueous extract of GP have a pro-fertility effect and possess anti-hyperglycemic activity within 14 days of treatment.

  12. Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice.

    PubMed

    Tian, Cai-Ming; Jiang, Xin; Ouyang, Xiao-Xi; Zhang, Ya-Ou; Xie, Wei-Dong

    2016-07-01

    The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of pAMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.

  13. Protective role of Hibiscus sabdariffa calyx extract against streptozotocin induced sperm damage in diabetic rats

    PubMed Central

    Idris, Muhd Hanis Md; Budin, Siti Balkis; Osman, Mohamad; Mohamed, Jamaludin

    2012-01-01

    Diabetes mellitus contributes to male sexual dysfunction and infertility by modulating oxidative damage. To date, a number of studies have demonstrated antioxidant properties of Hibiscus sabdariffa Linn. This study was designed to investigate the effects of H. sabdariffa UKMR-2 variety on sperm functioning of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were allotted into four groups, namely control group (C), H. sabdariffa extract (HSE) group, diabetes group (D) and diabetes plus HSE group (D+HSE). HSE (100 mg/ kg/body weight) was administered orally for 28 consecutive days. After 28-days of supplementation, the rats were sacrificed to obtain epididymal sperm. Administration of HSE significantly lowered the level of fasting blood glucose and increased plasma insulin level in D+HSE group as compared to D group (p<0.05). Sperm quality in the D+HSE group was improved with significantly higher sperm concentrations (p<0.05) and sperm motility (p<0.001) as well as lower percentage of sperm abnormality (p<0.05) as compared to the diabetic group. Plasma follicle-stimulating hormone (FSH) level was significantly elevated (p<0.05) in D+HSE group than in D group while no significant alteration in plasma testosterone and luteinizing hormone (LH) level were seen between groups. In conclusion, this study suggested that H. sabdariffa UKMR-2 variety has a potential protective role against diabetes-induced sperm damage. PMID:27847454

  14. Effect of Bauhinia holophylla treatment in Streptozotocin-induced diabetic rats.

    PubMed

    Pinheiro, Marcelo S; Rodrigues, Luhara S; S, Leila; Moraes-Souza, Rafaianne Q; Soares, Thaigra S; Américo, Madileine F; Campos, Kleber E; Damasceno, Débora C; Volpato, Gustavo T

    2017-02-16

    Bauhinia holophylla, commonly known as "cow's hoof", is widely used in Brazilian folk medicine for the diabetes treatment. Therefore, the aim of this study was at evaluating the aqueous extract effect of Bauhinia holophylla leaves treatment on the streptozotocin-induced diabetic rats. Diabetes was induced by Streptozotocin (40 mg/Kg) in female Wistar rats. Oral administration of aqueous extract of Bauhinia holophylla leaves was given to non-diabetic and diabetic rats at a dose of 400 mg/kg during 21 days. On day 17 of treatment, the Oral Glucose Tolerance Test was performed to determine the area under the curve. At the end of the treatment, the animals were anesthetized and blood was collected for serum biochemical parameters analysis. After treatment with Bauhinia holophylla extract, non-diabetic and diabetic rats presented no glycemic changes. On the other hand, the plant treatment decreased body weight and increased ALT and AST activities. In conclusion, the treatment with aqueous extract of B. holophylla leaves given to diabetic rats presented no hypoglycemic effect in nondiabetic animals and no antidiabetic effect in diabetic animals with the doses studied. In addition, the diabetic animals treated with the B. holophylla extract showed inconvenient effects and its indiscriminate consumption requires particular carefulness.

  15. The Ultrastructural Changes of the Sertoli and Leydig Cells Following Streptozotocin Induced Diabetes

    PubMed Central

    Kianifard, Davoud; Sadrkhanlou, Rajab Ali; Hasanzadeh, Shapour

    2012-01-01

    Objective(s) This investigation was conducted to evaluate the effects of diabetes on the structure and function of testicular tissue. Materials and Methods Diabetes was induced in male adult rats by a single intraperitoneal injection of streptozotocin. Body and testicular weight, hormonal analyses, histological and ultrastructural analyses were measured. Results The body and testicular weights were dropped significantly (P< 0.05) in diabetic rats in comparison with control rats. On the other hand, in diabetic rats, the blood glucose level increased significantly (P< 0.05). The blood plasma levels of testosterone, 17-β estradiol, progesterone, FSH and LH were reduced in diabetic rats. Histomorphological studies were revealed reduction in diameter of seminiferous tubules and germinal epithelium height, edema in interstitial tissue, germ cell depletion, decrease in cellular population and activity with disruption of spermatogenesis in diabetic rats. Ultrastructural study showed the mitochondrial change and reduction of smooth endoplasmic reticulum in Sertoli and presence of lipid droplets in Leydig cells of diabetic rat’s testes. Conclusion The results of the present study confirmed that, the ultrastructural changes of Sertoli and Leydig cells, brought about by streptozotocin induced diabetes, because of the alterations in pituitary gonadotropins, and these changes influence the normal spermatogenesis in rats. PMID:23493249

  16. Antihyperglycaemic effect of 'Ilogen-Excel', an ayurvedic herbal formulation in streptozotocin-induced diabetes mellitus.

    PubMed

    Umamaheswari, Selvaraj; Mainzen Prince, Ponnaian Stanely

    2007-01-01

    'Ilogen-Excel', an Ayurvedic herbal formulation is composed of eight medicinal plants (Curcuma longa, Strychnos potatorum, Salacia oblonga, Tinospora cordifolia, Vetivelia zizanioides, Coscinium fenestratum, Andrographis paniculata and Mimosa pudica). The present study evaluates the antihyperglycemic effect of 'Ilogen-Excel' in streptozotocin induced diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg/kg body weight). Oral administration of 'Ilogen-Excel' (50 mg/kg and 100 mg/kg) for 60 days resulted in significantly lowered levels of blood glucose and significantly increased levels of plasma insulin, hepatic glycogen and total hemoglobin. 'Ilogen-Excel' administration also decreased the levels of glycosylated hemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and vitamin E in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of 'Ilogen-Excel'. Administration of insulin normalized all the biochemical parameters studied in diabetic rats. The effect at a dose of 100 mg/kg was more pronounced than 50 mg/kg and brought back all the parameters to near normal levels. Thus, our study shows the antihyperglycemic effects of 'Ilogen-Excel' in STZ-induced diabetic rats. Our study also shows that combined therapy is better than individual therapy.

  17. Interleukin-1 promotes hyperglycemia and insulitis in mice normally resistant to streptozotocin-induced diabetes.

    PubMed Central

    Zunino, S. J.; Simons, L. F.; Sambrook, J. F.; Gething, M. J.

    1994-01-01

    By administering physiological doses of interleukin-1 (IL-1) concurrently with multiple low doses of the beta cell toxin streptozotocin (MSZ), we observed an augmentation of diabetes by IL-1 in four different strains of mice. Augmentation of hyperglycemia by IL-1 was most prominent in the two MSZ-resistant mouse strains Balb/cJ and A/J. Furthermore, concurrent treatment with IL-1 and MSZ rendered these MSZ-resistant mice susceptible to the development of significant insulitis when compared to mice treated with MSZ alone. Development of insulitis was dependent upon the dose of IL-1; it was only observed at an IL-1 dose of 250 ng/kg body weight. Analysis of the leukocytic infiltrate in the islets of mice after treatment with 250 ng/kg IL-1 plus MSZ revealed the presence of L3T4+ and Lyt-2+ T lymphocytes. Administration of MSZ alone or IL-1 alone did not produce diabetes in the MSZ-resistant mice, indicating that neither of these agents was toxic to the beta cells by itself. We conclude that IL-1 synergizes with MSZ to augment diabetes in mice that are normally resistant to the diabetogenic effects of MSZ. Images Figure 3 Figure 4 PMID:8080048

  18. Ameliorative Effect of Zinc Oxide Nanoparticles on Antioxidants and Sperm Characteristics in Streptozotocin-Induced Diabetic Rat Testes.

    PubMed

    Afifi, Mohamed; Almaghrabi, Omar A; Kadasa, Naif Mohammed

    2015-01-01

    The present study investigated the impact of zinc oxide nanoparticles (ZnONPs) on the oxidative status and sperm characteristics in diabetic rat testicular tissue. Forty male albino rats were used in this study; 10 of them served as a control and 30 rats were injected with a single dose (100 mg/kg) of streptozotocin intraperitoneally. They were subdivided into diabetic, diabetic + ZnONPs (10 mg/kg B.W.), and diabetic and cotreated with ZnONPs + insulin groups. The sperm count and motility were assessed. The activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRD), and Glutathion-S-Transferase (GST) were determined in the testicular tissue. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the testicular tissue. Sperm count and motility increased in ZnONPs treated diabetic rats. A significant increase in the activity and mRNA expression of SOD, CAT, GPx, GRD, and GST was shown in ZnONPs treated diabetic rats. MDA significantly decreased, while GSH increased in testicular tissue of ZnONPs treated diabetic rats. It was concluded that ZnONPs either alone or in combination with insulin have the ability to increase the sperm count and motility and protect the testicular tissue against the oxidative stress induced by diabetes in rats.

  19. Dietary supplementation with astaxanthin may ameliorate sperm parameters and DNA integrity in streptozotocin-induced diabetic rats

    PubMed Central

    Bahmanzadeh, Maryam; Vahidinia, Aliasghar; Mehdinejadiani, Shayesteh; Shokri, Saeed

    2016-01-01

    Objective Diabetes mellitus (DM) is known to cause many systemic complications as well as male infertility. Astaxanthin (ASTX) is a powerful antioxidant that is involved in a variety of biologically active processes, including those with anti-diabetes effects. The present study investigates the effect of ASTX on the spermatozoa function in streptozotocin (STZ)-induced diabetic rats. Methods We divided 30 adult rats into three groups (10 rats per group), with a control group that received corn oil mixed with chow. DM was induced by intra-peritoneal injection of STZ. Eight weeks after the STZ injection, half of the diabetic animals were used as diabetic controls, and the rest were treated with ASTX for 56 days. Then the parameters and chromatin integrity of the epididymal sperm were analyzed using chromomycin A3, toluidine blue (TB), and acridine orange (AO) staining. Results The count, viability, and motility of the epididymal sperm were decreased significantly in the STZ group in comparison with the control group (count and viability, p<0.001; motility, p<0.001;0.01). ASTX increased normal morphology and viable spermatozoa compared to the STZ group (morphology, p=0.001; viability, p<0.001;0.05). The percentage of abnormal chromatins in TB and AO staining was higher in the STZ group compared to the control group (p<0.001;0.001). The mean percentage of TB and AO positive spermatozoa in STZ rats was significantly lower in the STZ+ASTX group (TB, p=0.001; AO, p<0.001;0.05). Conclusion This study observed that in vivo ASTX treatment partially attenuates some detrimental effect of diabetes. Conversely, ASTX improved sperm viability, normal morphology, and DNA integrity. PMID:27358826

  20. Ameliorative Effect of Zinc Oxide Nanoparticles on Antioxidants and Sperm Characteristics in Streptozotocin-Induced Diabetic Rat Testes

    PubMed Central

    Afifi, Mohamed; Almaghrabi, Omar A.; Kadasa, Naif Mohammed

    2015-01-01

    The present study investigated the impact of zinc oxide nanoparticles (ZnONPs) on the oxidative status and sperm characteristics in diabetic rat testicular tissue. Forty male albino rats were used in this study; 10 of them served as a control and 30 rats were injected with a single dose (100 mg/kg) of streptozotocin intraperitoneally. They were subdivided into diabetic, diabetic + ZnONPs (10 mg/kg B.W.), and diabetic and cotreated with ZnONPs + insulin groups. The sperm count and motility were assessed. The activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRD), and Glutathion-S-Transferase (GST) were determined in the testicular tissue. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the testicular tissue. Sperm count and motility increased in ZnONPs treated diabetic rats. A significant increase in the activity and mRNA expression of SOD, CAT, GPx, GRD, and GST was shown in ZnONPs treated diabetic rats. MDA significantly decreased, while GSH increased in testicular tissue of ZnONPs treated diabetic rats. It was concluded that ZnONPs either alone or in combination with insulin have the ability to increase the sperm count and motility and protect the testicular tissue against the oxidative stress induced by diabetes in rats. PMID:26581756

  1. Protective effects of moderate exercise with dietary vitamin C and E on blood antioxidative defense mechanism in rats with streptozotocin-induced diabetes.

    PubMed

    Naziroğlu, Mustafa; Butterworth, Peter J

    2005-04-01

    Daily moderate exercise and supplementation of vitamins C and E (VCE) can be beneficial in diabetes by ameliorating the effects of free radical production. The present study sought to analyze the effect of moderate exercise accompanying VCE supplementation on lipid peroxidation (LP) and antioxidative systems in the blood of streptozotocin-induced diabetic rats. Forty female Wistar rats were randomly divided 4 groups. The 1st and 2nd groups served as the control and diabetic groups, respectively. The 3rd group was the diabetic-exercise group. The 4th group, also diabetic-exercise rats, received VCE-supplemented feed. Animals in the exercised groups were moderately exercised on a treadmill 5 days a week for 3 weeks. Diabetes was induced on Day 0 of the exercise. Plasma and red blood cell (RBC) samples were taken from all animals on Day 20. Glutathione peroxidase, catalase, and reduced glutathione levels in plasma and RBCs, and vitamins A, E, and beta-carotene in plasma were lower in diabetic rats than in control animals, whereas there was a significant increase in platelet counts in both plasma and RBC LP levels. The decreased antioxidant enzymes and vitamins, and the increased LP levels and WBC counts, did improve through exercise only, although their levels were mostly increased by exercise + VCE supplementation. There were no significant changes in the hemoglobin and hematocrit values in the 4 groups. In conclusion, these data demonstrate an increase in LP in the blood of diabetic animals whereas there was a decrease in the antioxidant vitamins and enzymes. However, dietary VCE with moderate exercise may strengthen the antioxidant defense system by decreasing reactive oxygen species.

  2. Beneficial effects of banana (Musa sp. var. elakki bale) flower and pseudostem on hyperglycemia and advanced glycation end-products (AGEs) in streptozotocin-induced diabetic rats.

    PubMed

    Bhaskar, Jamuna J; Shobha, Mysore S; Sambaiah, Kari; Salimath, Paramahans V

    2011-09-01

    Diabetes is a chronic health problem and major cause of death in most of the countries. Diet management plays an important role in controlling diabetes and its complications along with insulin and drugs. We have examined the effect of banana (Musa sp. var. elakki bale) flower and pseudostem on hyperglycemia and advanced glycation end-products (AGEs) in streptozotocin-induced diabetic rats. Our results indicated that banana flower and pseudostem have low glycemic index and have a high content of dietary fiber and antioxidants. Diabetic symptoms like hyperglycemia, polyuria, polyphagia, polydipsia, urine sugar, and body weight were ameliorated in banana flower- and pseudostem-treated rats. Increased glomerular filtration rate in the diabetic group (5.1 ± 0.22 ml/min) was decreased in banana flower-fed (2.5 ± 0.37 ml/min) and pseudostem-fed (3.0 ± 0.45 ml/min) groups and were significant at P < 0.001 and P < 0.01, respectively. Fructosamine and AGEs formed during diabetes were inhibited in treated groups when compared with the diabetic group. The diabetic group showed 11.5 ± 0.64 μg of AGEs/mg protein in kidney, whereas, in banana flower- and pseudostem-fed groups, it was reduced to 9.21 ± 0.32 and 9.29 ± 0.24 μg/mg protein, respectively, and were significant at P < 0.01. These findings suggest that banana flower and pseudostem have anti-diabetic and anti-AGEs properties and are beneficial as food supplements for diabetics.

  3. Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model.

    PubMed

    Wu, Jiangchun; Wang, Ruobing; Ye, Zhouheng; Sun, Xuejun; Chen, Zeli; Xia, Fangzhou; Sun, Qinglei; Liu, Lin

    2015-10-16

    As the commonest complication of diabetes mellitus (DM), diabetic retinopathy (DR) is a neuro-vascular disease with chronic inflammatory. Methane could exert potential therapeutic interest in inflammatory pathologies in previous studies. Our study aims to evaluate the protective effects of methane-rich saline on DR and investigate the potential role of related MicroRNA (miRNA) in diabetic rats. Streptozotocin-induced diabetic Sprague-Dawley rats were injected intraperitoneally with methane-rich or normal saline (5 ml/kg) daily for eight weeks. Morphology changes and blood-retinal barrier (BRB) permeability were assessed by hematoxylin eosin staining and Evans blue leakage. Retinal inflammatory cytokines levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL1-β) were evaluated by immunohistochemistry. Retinal protein expressions of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined by western blotting. Retinal miRNA expressions were examined by miRNA-specific microarray, verified by quantitative RT-PCR and predicted by GO enrichment and KEGG pathway analysis. There was no significant changes in blood glucose level and body weight of diabetic rats with methane-rich or normal saline treatment, but the decreased retinal thickness, retinal ganglial cell loss and BRB breakdown were all significantly suppressed by methane treatment. DM-induced retinal overexpressions of TNF-α, IL-1β, GFAP and VEGF were also significantly ameliorated. Moreover, the methane treatment significantly up-regulated retinal levels of miR-192-5p (related to apoptosis and tyrosine kinase signaling pathway) and miR-335 (related to proliferation, oxidative stress and leukocyte). Methane exerts protective effect on DR via anti-inflammation, which may be related to the regulatory mechanism of miRNAs.

  4. Modulatory influence of Parkia biglobosa protein isolate on testosterone and biomarkers of oxidative stress in brain and testes of streptozotocin-induced diabetic male rats

    PubMed Central

    Ogunyinka, Bolajoko Idiat; Oyinloye, Babatunji Emmanuel; Osunsanmi, Foluso Oluwagbemiga; Opoku, Andrew Rowland; Kappo, Abidemi Paul

    2016-01-01

    Parkia biglobosa seed an important household spice commonly consumed in Nigeria is believed to possess antioxidant activity that may exert modulatory effects in diabetes and diabetic complications. This study investigated the modulatory potential of Parkia biglobosa protein isolate (PBPi) on serum testosterone (sTT) level as well as its influence on biomarkers of oxidative stress in brain and testes of streptozotocin-induced diabetic male rats. Animals were made diabetic by single intraperitoneal administration of streptozotocin (STZ; 60 mg/kg body weight). PBPi (200 or 400 mg/kg body weight) was given orally by gavage or insulin (5 U/kg, i.p.) was administered daily to STZ-induced diabetic rats for 28 days. The results revealed a significant elevation in thiobarbituric acid reactive substances (TBARS) levels in the brain and testes of diabetic rats. This was closely associated with a concomitant reduction in levels of sTT and reduced testes weight, a noticeable decline in the glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) as well as total glutathione (Total GSH) level in the brain and testes of diabetic rats. Interestingly, treatment with PBPi efficiently prevented the alterations witnessed in the serum sTT and also ameliorated various alterations in the biomarkers of oxidative stress (TBARS, Total GSH, GST, SOD and CAT) in brain and testes of diabetic rats. These results provide evidence that PBPi could protect the brain and testicular tissues against oxidative stress induced by STZ, via modulation of serum testosterone concentration and also by enhancing antioxidant defence system in STZ-diabetic rats. PMID:27785334

  5. Autophagy Is Impaired in Neutrophils from Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Kuwabara, Wilson Mitsuo Tatagiba; Curi, Rui; Alba-Loureiro, Tatiana Carolina

    2017-01-01

    We tested the hypothesis that changes reported on functions of neutrophils from streptozotocin-induced diabetic rats involve autophagy impairment. Wistar rats were rendered diabetic by streptozotocin injection (65 mg/kg, i.v.), and the measurements were carried out 2 weeks afterward. Neutrophils were collected through intraperitoneal cavity lavage after 4 h of i.p. oyster glycogen type 2 injection. Neutrophils cultured with PMA (20 nM) for 1 h were used for analysis of plasma membrane integrity, DNA fragmentation, and mitochondrial depolarization by flow cytometry; expression of Atg5, Atg14, Beclin1, LC3BII, and Rab9 by RT-PCR; the contents of caspase 3, LC3BII/LC3BI, and pS6 by western blotting; ATP content by fluorescence essay; reactive oxygen species production by chemiluminescence (Luminol), and autophagy by immunofluorescence tracking LC3B cleavage. Herein, neutrophils from diabetic rats had high DNA fragmentation, depolarization of mitochondrial membrane, low content of ATP, and high content of cleaved caspase 3 after PMA stimulation. Neutrophils from diabetic rats also had low expression of LC3B, failed to increase the expression of Rab9 and Atg14 induced by PMA stimulation. Neutrophils from diabetic animals also had low cleavage of LC3BI to LC3BII and do not present punctate structures that label autophagosomal membranes after stimulus. The changes of neutrophil function reported in diabetic rats do involve impaired autophagy. The suppression of autophagy in neutrophils from diabetic rats may be associated with the activation of the mTOR signaling as indicated by the high content of pS6. PMID:28163707

  6. Dracaena arborea alleviates ultra-structural spermatogenic alterations in streptozotocin-induced diabetic rats

    PubMed Central

    2013-01-01

    Background Infertility is a common complication in diabetic men and experimental animals, mainly due to loss of germ cells by apoptotic cell death. The aim of this study was to evaluate the effects of aqueous and ethanol extracts of Dracaena arborea in streptozotocin-induced ultra-structural spermatogenic alterations in Wistar rats. Methods Diabetic animals were orally treated with Millipore water (10 ml/kg), sildenafil citrate (1.44 mg/kg) or Dracaena arborea aqueous (500 mg/kg) and ethanol (100 mg/kg) extracts for three weeks. A group of non diabetic rats received Millipore water (10 ml/kg) and served as healthy control group. Blood glucose was monitored at the beginning and the end of the study. One day after the last treatment, animals were sacrificed and the testes immediately removed were morphologically observed and prepared for electron microscopy analysis of spermatogenesis. Results Our results showed that Dracaena arborea was devoid of any anti-hyperglycemic activity. In the untreated diabetic rats, hyperglycemia severely damaged the testes morphology as well as the spermatogenic process as evidenced by the: thickness of basement membrane of the seminiferous tubule; mitochondria alteration; abnormal spermatocyte cells displaying polymorphous nuclei, cytoplasmic vacuolization and necrosis; and disorganization and degeneration of sperm germ cells. Administration of sildenafil citrate and Dracaena arborea extracts to the diabetic rats improved testes morphology and reversed, although not completely, the impairment of spermatogenesis; this alleviating effect was more pronounced in animals treated with the aqueous extract (500 mg/kg) of Dracaena arborea. Conclusion Dracaena arborea improves testes morphology and restores spermatogenesis in type 1 diabetic rats, without having major anti-hyperglycemic properties. These effects could be attributed to saponins, flavonoids, phenols and sterols revealed in this plant, which could be a useful component

  7. Hypoglycemic activity of Hemidesmus indicus R. Br. on streptozotocin-induced diabetic rats

    PubMed Central

    Gayathri, Mahalingam; Kannabiran, Krishnan

    2008-01-01

    OBJECTIVE: To evaluate the antidiabetic activity of an aqueous extract of the roots of Hemidesmus indicus on blood glucose, serum electrolytes, serum marker enzymes, liver microsomal P-450 enzymes, and lipid peroxidation in the liver and kidney of streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Effect of H. indicus extract on blood glucose was studied with fed, fasted and glucose-loaded diabetic and nondiabetic rat models. The effect of the extract on serum electrolytes, serum levels of key glucose metabolizing enzymes, hepatic microsomal protein and hepatic cytochrome P-450-dependent mono-oxygenase enzyme systems and lipid peroxidation in the liver and kidney of diabetic rats. One way analysis of variance and Duncan's multiple range test was used for statistical analysis. RESULTS: Oral administration of H. indicus aqueous extract to fed, fasted and glucose-loaded diabetic rats decreased blood glucose level significantly at 5 h and restored serum electrolytes, glycolytic enzymes and hepatic cytochrome P-450-dependent enzyme systems by preventing the formation of liver and kidney lipid peroxides at the end of 12 weeks of the study period. CONCLUSION: From the studies, it can be concluded that the aqueous extract of the roots of H. indicus at a dosage of 500 mg/kg/day exhibits significant antidiabetic activity. It restores the concentrations of electrolytes, glucose metabolizing enzymes, hepatic microsomal protein and hepatic cytochrome P-450-dependent mono-oxygenase enzyme systems to near normal level and also corrects the related metabolic alterations in experimentally induced diabetic rats. H. indicus administration also decreased liver and kidney lipid peroxidation products. On the basis of our findings, H. indicus could be used as an antidiabetic and antioxidant agent for the prevention and treatment of diabetes mellitus. PMID:19902032

  8. Responsiveness of renal glomeruli to adenosine in streptozotocin-induced diabetic rats dependent on hyperglycaemia level.

    PubMed

    Szczepańska-Konkel, M; Jankowski, M; Stiepanow-Trzeciak, A; Rudzik, A; Pawełczyk, T; Angielski, S

    2003-03-01

    Glomerular filtration rate (GFR) in response to adenosine precursor, NAD, and glomeruli contractility in response to adenosine were evaluated in streptozotocin-induced diabetic rats with severe (blood glucose 27.8 +/- 1.2 mmol/L) and moderate hyperglycaemia (18.2 +/- 0.9 mmol/L) compared with nondiabetic (ND)-rats. In anaesthetised rats, basal GFR was greater in moderately diabetic rats compared with severely diabetic rats (p < 0.05) and ND-rats (p < 0.02). Intravenous infusion of 5 nmol x min(-1) x kg(-1) NAD reduced GFR and renal plasma flow (RPF) in diabetic rats but had no effect on these parameters in ND-rats. Moreover, NAD-induced reduction of GFR and RPF was greater in rats with severe diabetes (41% and 30%, respectively) than in with moderate diabetes (25% and 26%, respectively). Theophylline (0.2 micromol x min(-1) x kg(-1) ) abolished renal response to NAD. Isolated glomeruli contraction in response to adenosine, assessed by glomerular 3H-inulin space reduction, was lowered in moderately diabetic-group and enhanced in severely diabetic-group. compared with ND-group (p < 0.05). Adenosine A1-receptor antagonist DPCPX inhibited adenosine-induced glomeruli contraction. This differential response of diabetic renal glomeruli to adenosine suggests that impaired glomerular contractility in response to adenosine could be responsible for hyperfiltration in moderate diabets, whereas, the increased adenosine-dependent contractility of glomeruli in severe diabetes may increase the risk of acute renal failure in this condition.

  9. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats

    PubMed Central

    Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara EF; Dutra, Bárbara A; Oliveira, Márcio V; de Magalhães, Amélia CM; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M

    2016-01-01

    This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. PMID:26490345

  10. Increased apoptosis of lactotrophs in streptozotocin-induced diabetic rats is followed by increased proliferation.

    PubMed

    Arroba, Ana I; Lechuga-Sancho, Alfonso M; Frago, Laura M; Argente, Jesús; Chowen, Julie A

    2006-10-01

    Poorly controlled diabetes mellitus can result in decreased prolactin production and thus problems with lactation, reproduction, and other physiological processes. This may be due to a loss of lactotrophs, as we have previously shown that long-term (8 weeks) poorly controlled streptozotocin-induced diabetes results in increased death of lactotrophs and that this most likely occurs through the activation of caspase-8 and the extrinsic cell death cascade. However, cell proliferation is also increased in the anterior pituitary at this time, although the cell type undergoing this proliferation and whether it is a response to the increased cell death remains unknown. In order to determine the time-course of increased cell death and proliferation in the anterior pituitary and if this is related to changes in tumor necrosis factor (TNF)-alpha, a cytokine involved in the activation of the extrinsic cell death pathway, rats were killed at 1, 4, 6, and 8 weeks after the induction of diabetes. Cell death was significantly increased after 4 weeks, as was caspase-8 activation, although circulating levels of TNF-alpha were increased as early as 1 week. Pituitary levels of TNF-alpha did not change significantly until 8 weeks after diabetes onset. Similarly, Western-blot analysis of proliferating cell nuclear antigen showed that anterior pituitary cell proliferation increased significantly 8 weeks after diabetes onset, with the majority of proliferating cells, as detected by BrdU incorporation, corresponding to lactotrophs. These results suggest that the increased death of lactotrophs in poorly controlled diabetic rats is followed by increased proliferation of this cell type, even when no treatment is given.

  11. Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats.

    PubMed

    Duarte, João M N; Carvalho, Rui A; Cunha, Rodrigo A; Gruetter, Rolf

    2009-10-01

    Type 1 diabetes can affect hippocampal function triggering cognitive impairment through unknown mechanisms. Caffeine consumption prevents hippocampal degeneration and memory dysfunction upon different insults and is also known to affect peripheral glucose metabolism. Thus we now characterized glucose transport and the neurochemical profile in the hippocampus of streptozotocin-induced diabetic rats using in vivo(1)H NMR spectroscopy and tested the effect of caffeine consumption thereupon. We found that hippocampal glucose content and transport were unaltered in diabetic rats, irrespective of caffeine consumption. However diabetic rats displayed alterations in their hippocampal neurochemical profile, which were normalized upon restoration of normoglycaemia, with the exception of myo-inositol that remained increased (36 +/- 5%, p < 0.01 compared to controls) likely reflecting osmolarity deregulation. Compared to controls, caffeine-consuming diabetic rats displayed increased hippocampal levels of myo-inositol (15 +/- 5%, p < 0.05) and taurine (23 +/- 4%, p < 0.01), supporting the ability of caffeine to control osmoregulation. Compared to controls, the hippocampus of diabetic rats displayed a reduced density of synaptic proteins syntaxin, synaptophysin and synaptosome-associated protein of 25 kDa (in average 18 +/- 1%, p < 0.05) as well increased glial fibrillary acidic protein (20 +/- 5%, p < 0.05), suggesting synaptic degeneration and astrogliosis, which were prevented by caffeine consumption. In conclusion, neurochemical alterations in the hippocampus of diabetic rats are not related to defects of glucose transport but likely reflect osmoregulatory adaptations caused by hyperglycemia. Furthermore, caffeine consumption affected this neurochemical adaptation to high glucose levels, which may contribute to its potential neuroprotective effects, namely preventing synaptic degeneration and astrogliosis.

  12. Propranolol improves cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Romana-Souza, Bruna; Nascimento, Adriana P; Monte-Alto-Costa, Andréa

    2009-06-02

    Sympathetic nerve failure has been proposed as a contributing factor in impaired cutaneous wound healing in diabetes mellitus. Nevertheless, no studies have shown whether beta-adrenoceptor blockade through beta-blocker (e.g., propranolol) administration may alter healing of diabetic cutaneous lesions. This study evaluated macro- and microscopically the effects of propranolol administration on cutaneous wound healing in streptozotocin-induced diabetic rats. Acute diabetes was induced by a single intraperitoneal injection of streptozotocin 14 days before wounding. Animals were treated with propranolol (50 mg/kg) dissolved in drinking water; controls received water only. Administration of beta-receptor antagonist began 1 day before wounding and was continued daily until euthanasia. A full-thickness excisional lesion (1 cm(2)) was created. The wound area was measured weekly and the animals were killed 14 days after wounding. Lesions and adjacent skin were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin-eosin, Sirius red, and toluidine blue, and immunostained for CD-68, alpha-smooth muscle actin and proliferating cell nuclear antigen. The wound area was significantly smaller in the propranolol-treated group than in the control group 7 and 14 days after wounding. Inflammatory cell numbers and metalloproteinase-9 levels were reduced in the propranolol-treated group compared to the control group 14 days after wounding. Cell proliferation, mast cell number, collagen deposition, blood vessel density, and nitric oxide levels were increased in the propranolol-treated group compared to the control group 14 days after wounding. Propranolol administration improves cutaneous wound healing of hyperglycemic diabetic rats by reducing the local inflammatory response and improving subsequent phases of the repair process.

  13. Hypoglycemic Activity of Fumaria parviflora in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Fathiazad, Fatemeh; Hamedeyazdan, Sanaz; Khosropanah, Mohamad Karim; Khaki, Arash

    2013-01-01

    Purpose: Fumaria parviflora Lam (Fumariaceae) has been used in traditional medicine in the treatment of several diseases such as diabetes. The present work was designed to evaluate the hypoglycaemic effects of methanolic extract (ME) of F. parviflora in normal and streptozotocin-induced diabetic rats. Methods: The rats used were allocated in six (I, II, III, IV, V and VI) experimental groups (n=5). Group I rats served as ‘normal control’ animals received distilled water and group II rats served as ‘diabetic control’ animals. Diabetes mellitus was induced in groups II, V and VI rats by intraperitoneal single injection of streptozotocin (STZ, 55 mg kg-1). Group V and VI rats were addi-tionally treated with ME (150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively) 24 hour post STZ injection, for seven consecutive days. Groups III and IV rats received only ME 150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively for seven days. The levels of blood glucose were determined using a Glucometer. Results: Administra-tion of F. parviflora extract showed a potent glucose lowering effect only on streptozo-tocin (STZ) induced diabetic rats below 100 mg/dl (P<0.001). However, no significant differences in the blood glucose levels were recorded between diabetic rats received 125 or 250 mg/kg of plant extracts. Conclusion: The findings of the study indicated that F. parviflora has significant hypoglycemic effect on STZ-induced diabetic rats with no effects on blood glucose levels of normal rats. PMID:24312837

  14. Metabolic profile changes in the testes of mice with streptozotocin-induced type 1 diabetes mellitus.

    PubMed

    Mallidis, C; Green, B D; Rogers, D; Agbaje, I M; Hollis, J; Migaud, M; Amigues, E; McClure, N; Browne, R A

    2009-04-01

    Contrary to the traditional view, recent studies suggest that diabetes mellitus has an adverse influence on male reproductive function. Our aim was to determine the effect of diabetes on the testicular environment by identifying and then assessing perturbations in small molecule metabolites. Testes were obtained from control and streptozotocin-induced diabetic C57BL/6 mice, 2, 4 and 8 weeks post-treatment. Diabetic status was confirmed by glycated haemoglobin, non-fasting blood glucose, physiological condition and body weight. A novel extraction procedure was utilized to obtain protein free, low-molecular weight, water soluble extracts which were then assessed using (1)H nuclear magnetic resonance spectroscopy. Principal component analysis of the derived profiles was used to classify any variations, and specific metabolites were identified based on their spectral pattern. Characteristic metabolite profiles were identified for control and type 1 diabetic animals with the most distinctive being from mice with the largest physical deterioration and loss of body weight. Eight streptozotocin-treated animals did not develop diabetes and displayed profiles similar to controls. Diabetic mice had decreases in creatine, choline and carnitine and increases in lactate, alanine and myo-inositol. Betaine levels were found to be increased in the majority of diabetic mice but decreased in a few animals with severe loss of body weight and physical condition. The association between perturbations in a number of small molecule metabolites known to be influential in sperm function, with diabetic status and physiological condition, adds further impetus to the proposal that diabetes influences important spermatogenic pathways and mechanisms in a subtle and previously unrecognized manner.

  15. Biomechanical characteristics of bone in streptozotocin-induced diabetic rats: An in-vivo randomized controlled experimental study

    PubMed Central

    Korres, Nektarios; Tsiridis, Eleftherios; Pavlou, George; Mitsoudis, Athanasios; Perrea, Despina N; Zoumbos, Aristedes B

    2013-01-01

    AIM: To investigate the in vivo effects of type I diabetes on the mechanical strength of tibial bone in a rodent model. METHODS: The biomechanical effect of diabetes on the structural integrity of the tibia in streptozotocin induced diabetic Wistar rats was analysed. Induction of diabetes was achieved by an intra-peritoneal injection and confirmed by measuring serial blood glucose levels (> 150 mg/dL). After 8 wk the tibiae were harvested and compared to a control group. Biomechanical analysis of harvested tibiae was performed using a three-point bending technique on a servo hydraulic MTS 858 MiniBionix frame. Maximum force applied to failure (N), stiffness (N × mm) and energy absorbed (N/mm) were recorded and plotted on load displacement curves. A displacement control loading mode of 1 mm/min was selected to simulate quasi-static loading conditions. Measurements from load-displacement curves were directly compared between groups. RESULTS: Fourteen streptozotocin induced diabetic Wistar rats were compared against nineteen non-diabetic controls. An average increase of 155.2 g in body weight was observed in the control group compared with only 5 g in the diabetic group during the experimental study period. Levels of blood glucose increased to 440.25 mg/dL in the diabetic group compared to 116.62 mg/dL in the control group.The biomechanical results demonstrate a highly significant reduction in the maximum load to failure from 69.5 N to 58 N in diabetic group compared to control (P = 0.011). Energy absorption to fracture was reduced from 28.2 N in the control group to 23.5 N in the diabetic group (P = 0.082). No significant differences were observed between the groups for bending stiffness. CONCLUSION: Streptozotocin-induced diabetes in rodents reduces the maximum force and energy absorption to failure of bone, suggesting a predisposition for fracture risk. PMID:23878780

  16. Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

    NASA Technical Reports Server (NTRS)

    Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

    1998-01-01

    We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

  17. Effect of Livingstone Potato (Plectranthus esculenthus N.E.Br) on Diabetes and Its Complications in Streptozotocin Induced Diabetes in Rats

    PubMed Central

    Eleazu, Kate Chinedum; Ironkwe, Adanma; Iroaganachi, Mercy Amarachi

    2014-01-01

    Background The effect of livingstone potato (Plectranthus esculenthus N.E.Br) on diabetes and its complications in Streptozotocin induced diabetic rats was investigated. The duration of the experiment was 4 weeks. Methods The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The liver and kidney function parameters in the serum of the rats were determined using Biosystem Kits. Results The diabetic rats given livingstonepotato incorporated feeds, had 129.7% decrease in their hyperglycemia with corresponding amelioration of their elevated urinary protein, sugars, specific gravity, renal growth, liver growth as well as 15.64% decrease in body weights compared with the nondiabetic rats that had 5.54% decrease in blood glucose and 20.39% increase in body weight unlike the diabetic control rats that had 18.34% decrease in blood glucose and 52.68% decrease in body weight. There were significant differences (P<0.05) in the relative liver, pancreas, and kidney weights of the diabetic rats given livingstone potato feeds compared with the diabetic control while there were no significant differences (P>0.05) in the relative heart weights of all the rats in the three different groups. In terms of liver and kidney function parameters, values obtained for the diabetic rats given livingstone potato incorporated feeds were not significantly different from that of the nondiabetic rats except for total bilurubin, aspartate transaminase, and creatinine (P>0.05) while they were significantly different from the values obtained for the diabetic control rats (P<0.05). In addition, the serum amylase of the diabetic control rats were significantly higher (P<0.05) than that of the nondiabetic and diabetic rats treated with livingstone potato incorporated feeds. Conclusion Results show the antidiabetic actions of livingstone potato and

  18. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    PubMed Central

    Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

    2015-01-01

    Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

  19. Endothelial dysfunction and metabolic control in streptozotocin-induced diabetic rats.

    PubMed

    Rodríguez-Mañas, L; Angulo, J; Peiró, C; Llergo, J L; Sánchez-Ferrer, A; López-Dóriga, P; Sánchez-Ferrer, C F

    1998-04-01

    1. The aim of this work was to study the influence of the metabolic control, estimated by the levels of glycosylated haemoglobin in total blood samples (HbA1c), in developing vascular endothelial dysfunction in streptozotocin-induced diabetic rats. Four groups of animals with different levels of insulin treatment were established, by determining HbA1c values in 5.5 to 7.4%, 7.5 to 9.4%, 9.5 to 12% and > 12%, respectively. 2. The parameters analysed were: (1) the endothelium-dependent relaxations to acetylcholine (ACh) in isolated aorta and mesenteric microvessels; (2) the vasodilator responses to exogenous nitric oxide (NO) in aorta: and (3) the existence of oxidative stress by studying the influence of the free radical scavenger superoxide dismutase (SOD) on the vasodilator responses to both ACh and NO. 3. In both isolated aortic segments and mesenteric microvessels, the endothelium-mediated concentration-dependent relaxant responses elicited by ACh were significantly decreased when the vessels were obtained from diabetic animals but only with HbA1c values higher than 7.5%. There was a high correlation between HbA1c levels and the impairment of ACh-induced relaxations, measured by pD2 values. 4. The concentration-dependent vasorelaxant responses to NO in endothelium-denuded aortic segments were significantly reduced only in vessels from diabetic animals with HbA1c values higher than 7.5%. Again, a very high correlation was found between the HbA1c values and pD2 for NO-evoked responses. 5. In the presence of SOD, the responses to ACh or NO were only increased in the segments from diabetic rats with HbA1c levels higher than 7.5%, but not in those from non-diabetic or diabetic rats with a good metabolic control (HbA1c levels <7.5%). 6. These results suggest the existence of: (1) a close relation between the degree of endothelial dysfunction and the metabolic control of diabetes, estimated by the levels of HbA1c; and (2) an increased production of superoxide anions in

  20. Effects of melatonin on streptozotocin-induced retina neuronal apoptosis in high blood glucose rat.

    PubMed

    Li, Xiaoyan; Zhang, Maonian; Tang, Weiqiang

    2013-03-01

    One of the main pathological symptoms of early diabetic retinal neuropathy is retina neuronal apoptosis. In the present work we investigated the effects of indoleamine hormone melatonin, a powerful free radical scavenger, on streptozotocin-induced retina neuronal cell apoptosis in high blood glucose rat. After melatonin treatment (10 mg/kg/day), tunel detection was used to monitor the apoptosis rate of neurons in the retinal ganglion cell layer; reversed quantitative PCR was used to measure the mRNA expression of retinal caspase-3, Mn superoxidase dismutase (SOD) and Cu-Zn SOD; and the activities of total SOD (T-SOD) and sub-type SOD was detected using xanthine oxidase enzymatic detection. Our data showed that melatonin treatment leads to a decrease of retinal cell apoptosis and the apoptotic index was (1.67 ± 0.54) % and (7.73 ± 0.95) % at 8 and 12 weeks after treatment. The relative quantitative (RQ) value for caspase-3 mRNA expression was (6.996 ± 1.192) and (7.267 ± 1.178) in melatonin group, which are much lower than the values of diabetic group (12.566 ± 2.272 and (14.297 ± 2.110) at 8 and 12 weeks, respectively) under the same condition. mRNA expression of Mn SOD and Cu-Zn SOD as well as their activities all decreased in the diabetic group compared with the control group. While melatonin treatment induced the expression of Mn SOD mRNA and a continual increase of Mn SOD activity as well as the activity and mRNA expression of Cu-Zn SOD at 12 weeks. Therefore, our results demonstrate that melatonin treatment prevented the decrease in mRNA expression of SOD and the increase in caspase-3 mRNA expression induced by diabetes thus exerts a beneficial effect on retina neuronal apoptosis.

  1. Glibenclamide or metformin combined with honey improves glycemic control in streptozotocin-induced diabetic rats.

    PubMed

    Erejuwa, Omotayo Owomofoyon; Sulaiman, Siti Amrah; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai Nainamohammed Salam; Salleh, Md Salzihan Md; Gurtu, Sunil

    2011-03-14

    Diabetes mellitus is associated with deterioration of glycemic control and progressive metabolic derangements. This study investigated the effect of honey as an adjunct to glibenclamide or metformin on glycemic control in streptozotocin-induced diabetic rats. Diabetes was induced in rats by streptozotocin. The diabetic rats were randomized into six groups and administered distilled water, honey, glibenclamide, glibenclamide and honey, metformin or metformin and honey. The animals were treated orally once daily for four weeks. The diabetic control rats showed hypoinsulinemia (0.27 ± 0.01 ng/ml), hyperglycemia (22.4 ± 1.0 mmol/L) and increased fructosamine (360.0 ± 15.6 µmol/L). Honey significantly increased insulin (0.41 ± 0.06 ng/ml), decreased hyperglycemia (12.3 ± 3.1 mmol/L) and fructosamine (304.5 ± 10.1 µmol/L). Although glibenclamide or metformin alone significantly (p < 0.05) reduced hyperglycemia, glibenclamide or metformin combined with honey produced significantly much lower blood glucose (8.8 ± 2.9 or 9.9 ± 3.3 mmol/L, respectively) compared to glibenclamide or metformin alone (13.9 ± 3.4 or 13.2 ± 2.9 mmol/L, respectively). Similarly, glibenclamide or metformin combined with honey produced significantly (p < 0.05) lower fructosamine levels (301.3 ± 19.5 or 285.8 ± 22.6 µmol/L, respectively) whereas glibenclamide or metformin alone did not decrease fructosamine (330.0 ± 29.9 or 314.6 ± 17.9 µmol/L, respectively). Besides, these drugs or their combination with honey increased insulin levels. Glibenclamide or metformin combined with honey also significantly reduced the elevated levels of creatinine, bilirubin, triglycerides, and VLDL cholesterol. These results indicate that combination of glibenclamide or metformin with honey improves glycemic control, and provides additional metabolic benefits, not achieved with either glibenclamide or metformin alone.

  2. Hypolipidemic and hypoglycemic activities of a oleanolic acid derivative from Malva parviflora on streptozotocin-induced diabetic mice.

    PubMed

    Gutiérrez, Rosa Martha Pérez

    2016-12-10

    One new oleanolic acid derivative, 2α,3β,23α,29α tetrahydroxyolean-12(13)-en-28-oic acid (1) was isolated from the aerial parts of Malva parviflora. Their structure was characterized by spectroscopic methods. The hypolipidemic and hypoglycemic activities of 1 was analyzed in in streptozotocin (STZ)-nicotinamide-induced type 2 diabetes in mice (MD) and type 1 diabetes in streptozotocin-induced diabetic mice (SD). Triterpene was administered orally at doses of 20 mg/kg for 4 weeks. Organ weight, body weight, glucose, fasting insulin, cholesterol-related lipid profile parameters, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP), glucokinase, hexokinase, glucose-6-phosphatase activities and glycogen in liver were measured after 4 weeks of treatment. The results indicated that 1 regulate glucose metabolism, lipid profile, lipid peroxidation, increased body weight, glucokinase and hexokinase activities inhibited triglycerides, total cholesterol, low density lipoproteins level, SGOT, SGPT, SALP, glycogen in liver and glucose-6-phosphatase. In addition, improvement of insulin resistance and protective effect for pancreatic β-cells, also 1 may changes the expression of pro-inflammatory cytokine (IL-6 and TNF-α levels) and enzymes (PAL2, COX-2, and LOX). The results suggest that 1 has hypolipidemic and hypoglycemic, anti-inflammatory, activities, improve insulin resistance and hepatic enzymes in streptozotocin-induced diabetic mice.

  3. Effect of Aqueous Extract of Tephrosia purpurea on Cardiovascular Complications and Cataract Associated with Streptozotocin-induced Diabetes in Rats

    PubMed Central

    Bhadada, Shraddha V.; Goyal, R. K.

    2015-01-01

    Tephrosia purpurea has been reported to possess antidiabetic activity, however, its effects on cardiovascular complications and cataract associated with diabetes have not been studied. The objective of the present study was to investigate the effects of aqueous extract of Tephrosia purpurea on cardiovascular complications and cataract associated with streptozotocin-induced diabetes in rats. Sprague Dawley rats of either sex were made diabetic with streptozotocin (45 mg/kg, i.v.). Treatment of aqueous extract of Tephrosia purpurea was given in the dose of 300 and 500 mg/kg/day, p.o for 8 weeks. Various hemodynamic (blood pressure, heart rate, +dp/dt, -dp/dt) and biochemical (serum glucose, cholesterol, triglycerides, creatinine, urea, lactate dehydrogenase and creatinine kinase) parameters were recorded after 8 weeks of the treatment. To evaluate cataract, various biochemical estimations were done in eye lens. Streptozotocin produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzymes, reduction in heart rate and cardiac hypertrophy in rats and all these changes were prevented by the treatment with aqueous extract of Tephrosia purpurea in both the doses. Streptozotocin also produced decrease in soluble protein and reduced glutathione in lens of rats that was prevented by aqueous extract of Tephrosia purpurea. Our data suggest that aqueous extract of Tephrosia purpurea prevents not only the streptozotocin-induced metabolic abnormalities but also cardiovascular complications as well as reduce the risk of development of cataract. PMID:26798165

  4. Effect of Aqueous Extract of Tephrosia purpurea on Cardiovascular Complications and Cataract Associated with Streptozotocin-induced Diabetes in Rats.

    PubMed

    Bhadada, Shraddha V; Goyal, R K

    2015-01-01

    Tephrosia purpurea has been reported to possess antidiabetic activity, however, its effects on cardiovascular complications and cataract associated with diabetes have not been studied. The objective of the present study was to investigate the effects of aqueous extract of Tephrosia purpurea on cardiovascular complications and cataract associated with streptozotocin-induced diabetes in rats. Sprague Dawley rats of either sex were made diabetic with streptozotocin (45 mg/kg, i.v.). Treatment of aqueous extract of Tephrosia purpurea was given in the dose of 300 and 500 mg/kg/day, p.o for 8 weeks. Various hemodynamic (blood pressure, heart rate, +dp/dt, -dp/dt) and biochemical (serum glucose, cholesterol, triglycerides, creatinine, urea, lactate dehydrogenase and creatinine kinase) parameters were recorded after 8 weeks of the treatment. To evaluate cataract, various biochemical estimations were done in eye lens. Streptozotocin produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzymes, reduction in heart rate and cardiac hypertrophy in rats and all these changes were prevented by the treatment with aqueous extract of Tephrosia purpurea in both the doses. Streptozotocin also produced decrease in soluble protein and reduced glutathione in lens of rats that was prevented by aqueous extract of Tephrosia purpurea. Our data suggest that aqueous extract of Tephrosia purpurea prevents not only the streptozotocin-induced metabolic abnormalities but also cardiovascular complications as well as reduce the risk of development of cataract.

  5. Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of streptozotocin-induced diabetic rats.

    PubMed

    Kamal, A; Artola, A; Biessels, G J; Gispen, W H; Ramakers, G M J

    2003-01-01

    Diabetes mellitus is associated with impairments of cognitive function both in humans and animal models. In diabetic rats cognitive deficits are related to alterations in activity-dependent synaptic plasticity in the hippocampus. Many similarities with the pathophysiology of normal brain aging have been noted, and the view emerges that the effects of diabetes on the brain are best described as "accelerated brain aging."In the present study we examined whether CA1 pyramidal neurons from streptozotocin-induced diabetic rats display an increased slow afterhyperpolarization, often considered as a hallmark of neuronal aging. We found no differences in resting membrane potential, input resistance, membrane time-constant, and action potential amplitude and duration between CA1 pyramidal neurons from streptozotocin-induced diabetic and age-matched control rats. During a train of action potentials, however, there is an increased broadening of the action potentials in diabetic animals, so-called "spike broadening." The amplitude of the slow afterhyperpolarization elicited by a train of action potentials is indeed increased in diabetic animals. Interestingly, when the slow afterhyperpolarization is elicited by a Ca(2+) spike, there is no difference between control and diabetic rats. This indicates that the increased slow afterhyperpolarization in diabetes is likely to be due to an increased Ca(2+) influx resulting from the increased spike broadening. These data underscore the notion that the diabetic brain at the neuronal level shares properties with brain aging.

  6. Preliminary studies on the hypoglycemic effect of Peganum harmala L. Seeds ethanol extract on normal and streptozotocin induced diabetic rats.

    PubMed

    Singh, Amar B; Chaturvedi, J P; Narender, T; Srivastava, Arvind K

    2008-10-01

    Peganum harmala L. (Zygophyllaceae) is a traditional medicine used for the treatment of variety of human ailments, including antidepression, hallucination, antileishmaniasis etc. We report for first time the hypoglycemic activity of the ethanolic extract of this plant at two dose levels of 150 and 250mg/kg bw in sucrose challenged normal as well as in rats with streptozotocin induced diabetes. The oral administration of ethanolic extract causes maximum fall of blood glucose level to 22.9% (p<0.05) and 29.4% (p<0.01) respectively with the two doses in normal and 30.3% (p<0.01) and 48.4% (p<0.001) in diabetic rats. The standard drug metformin treated group showed 28.0% (p<0.01) and 45.5% (p<0.001) respectively in normal and diabetic rats. The above results show that the ethanolic extract of P. harmala is as effective as metformin in reducing the blood glucose levels of normoglycemic and streptozotocin-induced diabetic rats.

  7. Enhanced synthesis and secretion of apolipoprotein E from sciatic nerves of streptozotocin-induced diabetic rats after injury

    SciTech Connect

    Ishibashi, S.; Yamada, N.; Oka, Y.; Shimano, H.; Mori, N.; Yoon, T.H.; Shimada, M.; Kanazawa, Y.; Akanuma, Y.; Murase, T.

    1988-08-30

    To elucidate the pathogenesis of diabetic neuropathy, synthesis and secretion of apolipoprotein E (apo E) from sciatic nerves after injury was studied in normal and streptozotocin-induced diabetic rats. Seven, 14, 28, 45 and 59 days after making crush injury on sciatic nerves with concomitant administration of streptozotocin (50 mg/kg body weight), the nerves were taken out and incubated with (/sup 35/S)methionine. The (/sup 35/S)labeled apo E was precipitated with specific antiserum. The amounts of apo E secreted into medium by nerves of diabetic rats were 7 times greater than those of non-diabetic rats 7 days after injury. This enhanced secretion of apo E was relatively selective for this protein, since the ratio of the immunoprecipitable apo E to the TCA preciptitable protein in the medium increased in diabetic rats. Intriguing possibility deduced from these results is that the secretion of apo E is involved in the development of diabetic neuropathy.

  8. Circulating advanced glycation peptides in streptozotocin-induced diabetic rats: evidence for preferential modification of IgG light chains.

    PubMed

    Gugliucci, A; Menini, T

    1998-01-01

    As the glycation/glycoxidation hypothesis for the genesis of diabetic complications is achieving widespread acceptance, much attention is being paid to the role of low molecular weight advanced glycation (AGE) adducts, as second generation glycating agents. We set out a study with the objective of attesting the presence of increased amounts of AGE-peptides in the circulation of streptozotocin-induced diabetic rats and to determine the nature of the plasma proteins which are main targets for advanced glycation. AGE (Ex 370/Em 440 nm) and pentosidine fluorescence (Ex 335/Em 385 nm) were significantly higher in plasma from diabetic rats after only one month of hyperglycemia as compared to controls (35 +/- 7 vs 25 +/- 2 AU, p< 0.05 and 54 +/- 14 vs 27 +/- 3 AU, p< 0.01 respectively). AGE-peptides (<10 kDa) were more than two-fold higher in diabetic animals. Immunoblots after SDS-PAGE of plasma proteins showed that AGE-IgG displayed a selective predominant increment in the same animals. When native rat IgG was incubated in the presence of AGE-peptides isolated from diabetic animals, AGE modification was already apparent after only 24 h of incubation, and was particularly important for light chains. AGE-immunoreactive light chains displayed an apparent increase in molecular weight. Aminoguanidine prevented, while copper enhanced AGE binding to IgG light chains. Our data validate the streptozotocin-induced diabetic rat as a model reproducing the presence of circulating AGE-peptides, give evidence that IgG are preferential targets for advanced glycation in plasma and suggest that this modification, mediated by AGE-peptides, can be prevented by aminoguanidine.

  9. In Vivo Evaluation of Anti Diabetic, Hypolipidemic, Antioxidative Activities of Saudi Date Seed Extract on Streptozotocin Induced Diabetic Rats

    PubMed Central

    Mohieldein, Abdelmarouf

    2016-01-01

    Introduction Phoenix dactylifera (date palm) is major fruit of gulf region. In folk medicine; dates have been traditionally use. The date seed is used as hypoglycaemic, expectorant, tonic, aphrodisiac, antidiarrheic and mouth hygiene. Aim This study intended to evaluate the anti-diabetic, hypolipidaemic and antioxidative activities of date seed extract in diabetes-induced rats. Materials and Methods Total of seven groups of rats, consisting of control rats and streptozotocin induced diabetic rats treated with aqueous seed extract in concentration of 100g/L in dosage of 10ml/day/rat. To evaluate the anti-diabetic property, glucose and weight was analysed weekly and at the end of eight week all rats were sacrificed. To evaluate the hypolipidaemic and antioxidative activities, serum cholesterol, triglyceride, malondialdehyde, superoxide dismutase, 8-hydroxy-2’-deoxyguanosine were estimated. Liver enzymes and kidney function tests were performed. Moreover to verify the glycaemic effect; glycated haemoglobin and serum insulin was performed. Results Aqueous seed extract in concentration of 100 gm/L in dosage of 10ml/day/rat brings a significant reduction of blood glucose levels in diabetic rats in comparison of control rats. There were significant differences in the investigated clinical chemistry and oxidative stress parameters between control and diabetic rats with both seed extract of Ajwa and Sukkari dates. Conclusion Present study verifies the antidiabetic property, of aqueous seed extracts of two different varieties of dates namely Ajwa and Sukkari of Kingdom of Saudi on streptozotocin induced Diabetic rats. Prolong treatments with the extract restores the function of liver and kidney and balance the oxidative stress condition in diabetic treated rats. PMID:27134893

  10. Palm oil tocotrienol fractions restore endothelium dependent relaxation in aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats.

    PubMed

    Muharis, Syed Putra; Top, Abdul Gapor Md; Murugan, Dharmani; Mustafa, Mohd Rais

    2010-03-01

    Diabetes and hypertension are closely associated with impaired endothelial function. Studies have demonstrated that regular consumption of edible palm oil may reverse endothelial dysfunction. The present study investigates the effect of palm oil fractions: tocotrienol rich fraction (TRF), alpha-tocopherol and refined palm olein (vitamin E-free fraction) on the vascular relaxation responses in the aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats (SHR). We hypothesize that the TRF and alpha-tocopherol fractions are able to improve endothelial function in both diabetic and hypertensive rat aortic tissue. A 1,1-diphenyl picryl hydrazyl assay was performed on the various palm oil fractions to evaluate their antioxidant activities. Endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxations were examined on streptozotocin-induced diabetic and SHR rat aorta following preincubation with the different fractions. In 1-diphenyl picryl hydrazyl antioxidant assay, TRF and alpha-tocopherol fractions exhibited a similar degree of activity while palm olein exhibited poor activity. TRF and alpha-tocopherol significantly improved acetylcholine-induced relaxations in both diabetic (TRF, 88.5% +/- 4.5%; alpha-tocopherol, 87.4% +/- 3.4%; vehicle, 65.0 +/- 1.6%) and SHR aorta (TRF, 72.1% +/- 7.9%; alpha-tocopherol, 69.8% +/- 4.0%, vehicle, 51.1% +/- 4.7%), while palm olein exhibited no observable effect. These results suggest that TRF and alpha-tocopherol fractions possess potent antioxidant activities and provide further support to the cardiovascular protective effects of palm oil vitamin E. TRF and alpha-tocopherol may potentially improve vascular endothelial function in diabetes and hypertension by their sparing effect on endothelium derived nitric oxide bioavailability.

  11. In Vivo Evaluation of the Visual Pathway in Streptozotocin-Induced Diabetes by Diffusion Tensor MRI and Contrast Enhanced MRI

    PubMed Central

    Kancherla, Swarupa; Kohler, William J.; van der Merwe, Yolandi

    2016-01-01

    Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI) was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively. PMID:27768755

  12. Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells.

    PubMed

    Seki, Masaaki; Tanaka, Takayuki; Nawa, Hiroyuki; Usui, Tomoaki; Fukuchi, Takeo; Ikeda, Kazuhito; Abe, Haruki; Takei, Nobuyuki

    2004-09-01

    Although neurotrophins have been assessed as candidate therapeutic agents for neural complications of diabetes, their involvement in diabetic retinopathy has not been fully characterized. We found that the protein and mRNA levels of brain-derived neurotrophic factor (BDNF) in streptozotocin-induced diabetic rat retinas were reduced to 49% (P < 0.005) and 74% (P < 0.05), respectively, of those of normal control animals. In addition, dopaminergic amacrine cells appeared to be degenerating in the diabetic rat retinas, as revealed by tyrosine hydroxylase (TH) immunoreactivity. Overall TH protein levels in the retina were decreased to one-half that of controls (P < 0.01), reflecting reductions in the density of dopaminergic amacrine cells and the intensity of TH immunoreactivity within them. To confirm the neuropathological implications of BDNF reduction, we administered BDNF protein into the vitreous cavities of diabetic rats. Intraocular administration of BDNF rescued dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of TH expression, demonstrating its therapeutic potential. These findings suggest that the early retinal neuropathy of diabetes involves the reduced expression of BDNF and can be ameliorated by an exogenous supply of this neurotrophin.

  13. Effect of Afobazole and Betaine on Cognitive Disorders in the Offspring of Rats with Streptozotocin-Induced Diabetes and Their Relationship with DNA Damage.

    PubMed

    Zabrodina, V V; Shreder, O V; Shreder, E D; Durnev, A D

    2016-07-01

    Cognitive activity in 60-day-old offspring of rats (intrauterine development in experimental streptozotocin-induced diabetes) was studied on the model of food-seeking behavior under conditions of free choice in a 6-arm maze. The formation of the food-procuring skill was significantly delayed, which attests to impairment of cognitive functions in these animals. Peroral administration of afobazole (10 and 50 mg/kg) and betaine (50 and 100 mg/kg) significantly and dose-dependently alleviated this disorder. Correlation analysis of the data on delayed formation of a food-procuring skill and results of DNA comet attests to a strong relationship between DNA damage in cells of the embryo and placenta during intrauterine development and cognitive dysfunction in the postnatal offspring of animals with streptozotocin-induced diabetes.

  14. Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats

    PubMed Central

    FATANI, AMAL JAMIL; AL-REJAIE, SALIM SALIH; ABUOHASHISH, HATEM MUSTAFA; AL-ASSAF, ABDULLAH; PARMAR, MIHIR YOGESHKUMAR; OLA, MOHAMMAD SHAMSUL; AHMED, MOHAMMED MAHBOOBUDDIN

    2015-01-01

    The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF

  15. Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats.

    PubMed

    Fatani, Amal Jamil; Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Al-Assaf, Abdullah; Parmar, Mihir Yogeshkumar; Ola, Mohammad Shamsul; Ahmed, Mohammed Mahboobuddin

    2015-05-01

    The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF

  16. Chronic Oral Pelargonidin Alleviates Streptozotocin-Induced Diabetic Neuropathic Hyperalgesia in Rat: Involvement of Oxidative Stress

    PubMed Central

    Mirshekar, Mohammadali; Roghani, Mehrdad; Khalili, Mohsen; Baluchnejadmojarad, Tourandokht; Arab Moazzen, Saiedeh

    2010-01-01

    Background: Diabetes mellitus in some clinical cases is accompanied with hyperalgesia. In this study, we evaluated the possible beneficial effect of chronic pelargonidin (PG) treatment on hyperalgesia in streptozotocin (STZ)-diabetic neuropathic rat. Methods: Male Wistar rats (n = 56) were divided into seven groups, i.e. control, diabetic, PG-treated control, PG (single- and multiple-dose)-treated diabetic, and sodium salicylate-treated control and diabetics. For induction of diabetes, STZ was injected i.p. at a single dose of 60 mg/kg. PG was orally administered at a dose of 10 mg/kg once and/or on alternate days for 8 weeks; 1 week after diabetes induction. After two months, hyperalgesia was assessed using standard formalin and hot tail immersion tests. Meanwhile, markers of oxidative stress in brain were measured. One-way analysis of variance was used for statistical analysis of the data. Results: Diabetic rats showed a marked chemical and thermal hyperalgesia, indicating that development of diabetic neuropathy and PG treatment (especially multiple-doses) significantly ameliorated the alteration in hyperalgesia (P<0.05-0.01) in diabetic rats as compared to untreated diabetics. PG (multiple doses) also significantly decreased diabetes-induced thiobarbituric acid reactive substances formation and non-significantly reversed elevation of nitrite level and reduction of antioxidant defensive enzyme superoxide dismutase. Conclusion: These results clearly suggest that PG prevents diabetic neuropathic hyperalgesia through attenuation of oxidative stress. PMID:20683496

  17. Urtica dioica leaves modulates muscarinic cholinergic system in the hippocampus of streptozotocin-induced diabetic mice.

    PubMed

    Patel, Sita Sharan; Parashar, Arun; Udayabanu, Malairaman

    2015-06-01

    Diabetes mellitus is a chronic metabolic disorder and has been associated with cognitive dysfunction. In our earlier study, chronic Urtica dioica (UD) treatment significantly ameliorated diabetes induced associative and spatial memory deficit in mice. The present study was designed to explore the effect of UD leaves extract on muscarinic cholinergic system, which has long been known to be involved in cognition. Streptozotocin (STZ) (50 mg/kg, i.p., consecutively for 5 days) was used to induce diabetes followed by treatment with UD extract (50 mg/kg, oral) or rosiglitazone (5 mg/kg, oral) for 8 weeks. STZ-induced diabetic mice showed significant reduction in hippocampal muscarinic acetylcholine receptor-1 and choline acetyltransferase expressions. Chronic diabetes significantly up-regulated the protein expression of acetylcholinesterase associated with oxidative stress in hippocampus. Besides, STZ-induced diabetic mice showed hypolocomotion with up-regulation of muscarinic acetylcholine receptor-4 expression in striatum. Chronic UD treatment significantly attenuated the cholinergic dysfunction and oxidative stress in the hippocampus of diabetic mice. UD had no effect on locomotor activity and muscarinic acetylcholine receptor-4 expression in striatum. In conclusion, UD leaves extract has potential to reverse diabetes mediated alteration in muscarinic cholinergic system in hippocampus and thereby improve memory functions.

  18. Mechanism of testicular protection of carvedilol in streptozotocin-induced diabetic rats

    PubMed Central

    Ramzy, Maggie M.; El-Sheikh, Azza A. K.; Kamel, Maha Y.; Abdelwahab, Soha A.; Morsy, Mohamed A.

    2014-01-01

    Aims: Male sub-fertility and infertility are major complications of diabetes mellitus. The non-selective β-blocker carvedilol has been reported to have favorable effects on some of the diabetic complications based on its antioxidant and anti-apoptotic effects. This study aims to evaluate the possible testicular protective effect of carvedilol in streptozotocin (STZ)-induced diabetic rat model and its possible mechanisms. Materials and Methods: Diabetes was induced by a single i.p. dose of 65 mg/kg of STZ. In parallel groups of diabetic rats, carvedilol in low and high doses (1 and 10 mg/kg/day orally) were administered for 4 weeks. Oxidative stress markers as reduced glutathione (GSH) and the product of lipid peroxidation; malondialdehyde (MDA) were evaluated in testicular homogenate. The level of expression of the apoptotic marker; caspase 3, was assessed using western blot, followed by densitometric analysis. Results: Induction of diabetes caused distortion of histological normal testicular structure, with decrease (P < 0.05) in GSH and increase (P < 0.05) in MDA, as well as induction of caspase 3 expression. Carvedilol in low or high doses reverted diabetes-induced histological damage, restored antioxidant activity and ameliorated caspase 3 expression. Conclusion: Carvedilol confers testicular protection against diabetes-induced damage through antioxidant and anti-apoptotic mechanisms. PMID:24741186

  19. Antioxidant Activities of Caralluma tuberculata on Streptozotocin-Induced Diabetic Rats.

    PubMed

    Poodineh, Jafar; Khazaei Feizabad, Abdurrashid; Nakhaee, Alireza

    2015-01-25

    Preclinical Research The aim of this study was to elucidate the antioxidant effects of Caralluma tuberculata (C. tuberculata) in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar rats with an intraperitoneal injection of STZ at dose of 60 mg/kg body weight. Three days after diabetes induction, powdered aerial part of plant at doses of 100 and 200 mg/kg body weight were gavaged orally for a period of 45 days. The diabetes significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and level of total thiol in liver, kidney, and heart of animals (P < 0.05). In contrast, a significant increase in the levels of protein carbonyl was observed in diabetic rats compared with control animals (P < 0.05). Oral treatment of diabetic rats with C. tuberculata showed ameliorative effects on blood glucose and markers of oxidative stress in a dose-dependent manner. Altered levels of all oxidative stress parameters in tissues of diabetic rats reverted back to those normal animals after the treatment with dose of 200  mg/kg /day of plant materials. It seems that the appropriate dose of C. tuberculata has both antihyperglycemic and antioxidant activities in STZ-induced diabetic rats. Therefore, it can have preventive properties on oxidative stress-induced diabetic complications. Drug Dev Res, 2014. © 2014 Wiley Periodicals, Inc.

  20. Antihyperglycemic effects of separate and composite extract of root of Musa paradisiaca and leaf of Coccinia indica in streptozotocin-induced diabetic male albino rat.

    PubMed

    Mallick, Chhanda; Chatterjee, Kausik; Guhabiswas, Mehuli; Ghosh, Debidas

    2007-02-16

    We evaluated the antihyperglycaemic properties of aqueous-methanolic (40:60) extract of root of Musa paradisiaca and leaf of Coccinia indica in separate as well as in composite manner by conducting experiment on streptozotocin-induced diabetic rats. We measured food and water intake ability, the fasting blood glucose level, glucose tolerance, activities of important carbohydrate metabolic enzymes like glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, hexokinase in liver along with quantification of glycogen in liver and in skeletal muscle and serum insulin level. We noted that after treatment of aqueous methanolic extract of above plant parts in separate as well as in composite manner at a concentration of 80 mg/100 g body weight/day to streptozotocin-induced diabetic rat resulted in a significant remedial effect on blood glucose level as well as carbohydrate metabolic enzymes and the quantity of liver and skeletal muscle glycogen. Serum insulin level that was diminished in streptozotocin-induced diabetic rat recovered significantly after the co-administration of extract of above plant parts. All the above parameters showed a more potent remedial effect after composite extract treatment with respect to separate treatment and none of the extract has any general metabolic toxicity induction.

  1. Antihyperglycaemic effects of ethanol extracts of Carica papaya and Pandanus amaryfollius leaf in streptozotocin-induced diabetic mice.

    PubMed

    Sasidharan, Sreenivasan; Sumathi, Vello; Jegathambigai, Naidu Rameshwar; Latha, Lachimanan Yoga

    2011-12-01

    Diabetes mellitus is a global disease that is increasing in an alarming rate. The present study was undertaken to study the antidiabetic effect of the ethanol extracts of Carica papaya and Pandanus amaryfollius on streptozotocin-induced diabetic mice. The results of the present study indicated that there was no significant difference in the body weight of the treated groups when compared to diabetic control. Whereas, there was significant (P < 0.05) decrease in the blood glucose level of the plant-treated groups compared to the diabetic control. Histologically the pancreas of the treated groups indicated significant regeneration of the β-cells when compared to the diabetic control. The liver tissues of the treated group indicated a reduction in fatty changes and pyknotic nucleus. The kidney tissues of the treated groups indicated significant recovery in the cuboidal tissue. The results from the phytochemical screening indicated the presence of flavonoids, alkaloids, saponin and tannin in C. papaya and P. amaryfollius. The antidiabetic effect of C. papaya and P. amaryfollius observed in the present study may be due to the presence of these phytochemicals.

  2. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes

    PubMed Central

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  3. Investigation of the in vivo antioxidative activity of Cynara scolymus (artichoke) leaf extract in the streptozotocin-induced diabetic rat.

    PubMed

    Magielse, Joanna; Verlaet, Annelies; Breynaert, Annelies; Keenoy, Begoña Manuel Y; Apers, Sandra; Pieters, Luc; Hermans, Nina

    2014-01-01

    The in vivo antioxidant activity of a quantified leaf extract of Cynara scolymus (artichoke) was studied. The aqueous artichoke leaf extract (ALE), containing 1.5% caffeoylquinic acid with chlorogenic acid being most abundant (0.30%), and luteolin-7-O-glucoside as major flavonoid (0.15%), was investigated by evaluating the effect on different oxidative stress biomarkers, after 3 wk oral supplementation in the streptozotocin-induced diabetic rat model. Apart from two test groups (0.2 g ALE/kg BW/day and 1 g ALE/kg BW/day, where BW is body weight), a healthy control group, untreated oxidative stress group, and vitamin E treated group (positive control) were included. A 0.2 g/kg BW/day of ALE decreased oxidative stress: malondialdehyde and 8-hydroxydeoxyguanosine levels significantly diminished, whereas erythrocyte glutathione levels significantly increased. A 1.0 g/kg BW/day ALE did not show higher antioxidant activity.

  4. A Comparison of Wound Healing Rate Following Treatment with Aftamed and Chlorine Dioxide Gels in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Al-Bayaty, Fouad; Abdulla, Mahmood Ameen

    2012-01-01

    Background and Purpose. This study aimed to evaluate the wound healing activities of Aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. Experimental Approach. Forty-eight Sprague Dawley rats were chosen for this study, divided into 4 groups. Diabetes was induced. Two-centimeter-diameter full-thickness skin excision wounds were created. Animals were topically treated twice daily. Groups 1, the diabetic control group, were treated with 0.2 mL of sterile distilled water. Group 2 served as a reference standard were treated with 0.2 mL of Intrasite gel. Groups 3 and 4 were treated with 0.2 mL of Aftamed and 0.2 mL of chlorine dioxide gels respectively. Granulation tissue was excised on the 10th day and processed for histological and biochemical analysis. The glutathione peroxidase ,superoxide dismutase activities and the malondialdehyde (MDA) levels were determined. Results. Aftamed-treated wounds exhibited significant increases in hydroxyproline, cellular proliferation, the number of blood vessels, and the level of collagen synthesis. Aftamed induced an increase in the free radical-scavenging enzyme activity and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in the MDA level. Conclusions. This study showed that Aftamed gel is able to significantly accelerate the process of wound healing in diabetic rats. PMID:22666291

  5. Activation of caspase 8 in the pituitaries of streptozotocin-induced diabetic rats: implication in increased apoptosis of lactotrophs.

    PubMed

    Arroba, Ana I; Frago, Laura M; Argente, Jesús; Chowen, Julie A

    2005-10-01

    Lactotroph cell death is increased in streptozotocin-induced diabetic rats. To determine the mechanism involved, cell death proteins were accessed in pituitaries of diabetic (streptozotocin at 65 mg/kg, 2 months evolution) and control male rats by Western blot analysis and double immunohistochemistry. The intact and cleaved forms of caspase 9 were increased in diabetic rat pituitaries compared with controls. Although the proforms of caspases 3, 6, and 7 were increased in diabetic rat pituitaries, their activated forms were either unchanged or decreased. Activation of these effector caspases may be blocked by the increased expression of X-chromosome-linked inhibitor of apoptosis protein (XIAP) in diabetic rat pituitaries. However, in diabetic rats, XIAP expression in lactotrophs was decreased, suggesting that this cell type is not protected. Caspase 8, p53, and nuclear factor kappaB were more highly activated in diabetic rat pituitaries, with caspase 8 colocalization in lactotrophs being increased. These results suggest that, in the pituitaries of diabetic rats, the cascades of normal cell turnover are partially inhibited, possibly via XIAP, and this may be cell specific. Furthermore, activation of the extrinsic cell-death pathway, including activation of caspase 8, may underlie the diabetes-associated increase in lactotroph death.

  6. Nardostachys jatamansi extract protects against cytokine-induced β-cell damage and streptozotocin-induced diabetes

    PubMed Central

    Song, Mi-Young; Bae, Ui-Jin; Lee, Bong-Hee; Kwon, Kang-Beom; Seo, Eun-A; Park, Sung-Joo; Kim, Min-Sun; Song, Ho-Joon; Kwon, Keun-Sang; Park, Jin-Woo; Ryu, Do-Gon; Park, Byung-Hyun

    2010-01-01

    AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin via a tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated rat islets were treated with interleukin-1β and interferon-γ to induce cytotoxicity. RESULTS: Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining of the islets. The diabetogenic effects of streptozotocin were completely abolished when mice were pretreated with NJE. Inhibition of streptozotocin-induced hyperglycemia by NJE was mediated by suppression of nuclear factor (NF)-κB activation. In addition, NJE protected against cytokine-mediated cytotoxicity. Incubation of RINm5F cells and islets with NJE resulted in a significant reduction in cytokine-induced NF-κB activation and downstream events, inducible nitric oxide synthase expression and nitric oxide production. The protective effect of NJE was further demonstrated by the normal insulin secretion of cytokine-treated islets in response to glucose. CONCLUSION: NJE provided resistance to pancreatic β-cell damage from cytokine or streptozotocin treatment. The β-cell protective effect of NJE is mediated by suppressing NF-κB activation. PMID:20614480

  7. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Kant, Vinay; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surendra K; Kumar, Dinesh

    2014-06-01

    Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics.

  8. Restoration of cardiomyocyte function in streptozotocin-induced diabetic rats after treatment with vanadate in a tea decoction.

    PubMed

    Clark, Tod A; Maddaford, Thane G; Tappia, Paramjit S; Heyliger, Clayton E; Ganguly, Pallab K; Pierce, Grant N

    2010-12-01

    Diabetes mellitus is associated with abnormal cardiomyocyte Ca(2+) transients and contractile performance. We investigated the possibility that an alteration in inositol trisphosphate/phospholipase C (IP₃/PLC) signalling may be involved in this dysfunction. Phosphatidic acid stimulates cardiomyocyte contraction through an IP₃/PLC signaling cascade. We also tested a novel therapeutic intervention to assess its efficacy in reversing any potential defects. Diabetes was induced in Sprague-Dawley rats by streptozotocin treatment and maintained for an 8 week experimental period. Active cell shortening was significantly depressed in cardiomyocytes obtained from diabetic and insulin-treated diabetic rats in comparison to normal control animals. Perfusion of the cells with phosphatidic acid induced an increase in contraction of control rat cardiomyocytes whereas its effect was inhibitory in cells from streptozotocin-induced diabetic rats. Diabetic rats were also treated orally with vanadate administered in a black tea extract (T/V) for the 8 week period. T/V treatment resulted in a contractile response that was not different from cells of control animals. Furthermore, cardiomyocytes from T/V-treated animals exhibited significantly improved Ca(2+) transients in comparison to diabetic animals and exhibited a normalized response to phosphatidic acid perfusion. It is concluded that a T/V glycemic therapy is capable of preventing the defect in IP₃/PLC signaling that occurs in diabetes and can restore normal cardiac contractile function.

  9. Attenuation of nonenzymatic glycation, hyperglycemia, and hyperlipidemia in streptozotocin-induced diabetic rats by chloroform leaf extract of Azadirachta indica

    PubMed Central

    Gutierrez, Rosa Martha Pérez; Gómez, Yolanda Gómez Y.; Guzman, Mónica Damián

    2011-01-01

    Background: The hypoglycemic effects of hexane, chloroform and methanol extracts of leaves of Azadirachta indica (AI) were evaluated by oral administration in streptozotocin-induced severe diabetic rats (SD). Materials and Methods: The effect of chronic oral administration of the extract for 28 days was evaluated in streptozotozin diabetic rats. Lipid peroxidation, glycogen content of liver and skeletal muscles, insulin, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), oxidized glutathione (GSSG) levels were determined. In addition, advanced glycation end product formation (AGEs) was evaluated. Results: The most active extracts were obtained with chloroform. Chloroform extract from AI shows increased levels of SOD, GSH, GSSG and CAT, hepatic glycogen content, glucose-6-phosphatase and insulin plasma levels, which also decreased the glucokinase (GK), lipid peroxidation and insulin resistance. The chloroform extract exhibited significant inhibitory activity against advanced glycation end product formation with an IC50 average range of 79.1 mg/ml. Conclusion: Azadirachta indica can improve hyperlipidemia and hyperinsulinema in streptozocin-induced diabetic rats and, therefore, AI can be potentially considered to be an antidiabetic-safe agent. PMID:21969798

  10. Short- and long-term effects of various Citrullus colocynthis seed extracts in normal and streptozotocin-induced diabetic rats.

    PubMed

    Benariba, Nabila; Djaziri, Rabeh; Zerriouh, Bouchra Hanane; Bellakhdar, Wafaa; Hupkens, Emeline; Boucherit, Zahia; Malaisse, Willy J

    2012-12-01

    In the light of previous findings, the major aim of the present study was to investigate the potential beneficial effects of various Citrullus colocynthis L. seed extracts on such variables as glucose tolerance, body weight gain, pancreas, liver, kidney, testis, epididymal fat and diaphragm muscle weight, as well as serum cholesterol, triglyceride, urea, creatinine, transaminases and alkaline phosphatase concentrations in an animal model of type-1 diabetes mellitus, i.e. streptozotocin-induced diabetic rats. For purpose of comparison, a comparable study was conducted in normal rats. Both the immediate and long-term effects of the plant extracts were assessed in rats injected daily, up to 3 weeks after the start of the experiments. The results of this study reinforce the view that both a crude aqueous extract and a n-butanol extract from the Citrullus colocynthis L. seeds may represent the best candidates in order to eventually identify a component suitable for the treatment of both type-1 and type-2 diabetic subjects.

  11. Studies on the Antidiabetic Activities of Cordyceps militaris Extract in Diet-Streptozotocin-Induced Diabetic Sprague-Dawley Rats

    PubMed Central

    Dong, Yuan; Jing, Tianjiao; Meng, Qingfan; Liu, Chungang; Hu, Shuang; Ma, Yihang; Liu, Yan; Lu, Jiahui; Cheng, Yingkun; Teng, Lirong

    2014-01-01

    Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities of Cordyceps militaris on diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin, Cordyceps militaris extracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum. Cordyceps militaris extracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection of Cordyceps militaris extracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively, Cordyceps militaris extract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment. PMID:24738047

  12. Effects of cytidine 5'-diphosphocholine (CDP-choline) on the thermal nociceptive threshold in streptozotocin-induced diabetic mice.

    PubMed

    Kamei, Junzo; Ohsawa, Masahiro; Miyata, Shigeo; Endo, Kazuki; Hayakawa, Hiroyuki

    2008-11-19

    Neuropathy accompanied by abnormal sensory perception is the most common complication in insulin-dependent and -independent diabetes mellitus. Since there are very few effective therapeutic regimens for sensory abnormalities in diabetes, we examined the effect of cytidine 5'-diphosphocholine (CDP)-choline on the thermal nociceptive threshold in streptozotocin-induced diabetic mice using the tail-flick test. Diabetic mice showed a shorter tail-flick latency at 1-4 weeks after streptozotocin treatment and a longer tail-flick latency after 8-12 weeks. This hyper- and hypoalgesia in diabetic mice was almost completely inhibited by daily treatment with CDP-choline (100 mg/kg/day, p.o.) beginning on the day of streptozotocin treatment. Daily treatment with CDP-choline beginning 5 weeks after streptozotocin treatment attenuated the development of hypoalgesia. Diabetic mice showed a significant increase in Na(+)-K(+)-ATPase activity at 3 weeks after streptozotocin treatment, whereas Na(+)-K(+)-ATPase activity was decreased at 12 weeks after treatment. These alterations were normalized by daily treatment with CDP-choline (100 mg/kg/day, p.o.) beginning the day of streptozotocin treatment. These results provide evidence to support the therapeutic potency of CDP-choline on the development of thermal hyper- and hypoalgesia and the progression of thermal hypoalgesia in diabetic mice. Moreover, these effects of CDP-choline may result from the normalization of Na(+)-K(+)-ATPase activity.

  13. Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats.

    PubMed

    Coppey, Lawrence J; Davidson, Eric P; Obrosov, Alexander; Yorek, Mark A

    2015-02-01

    The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy.

  14. The protective effects of insulin and natural honey against hippocampal cell death in streptozotocin-induced diabetic rats.

    PubMed

    Jafari Anarkooli, Iraj; Barzegar Ganji, Hossein; Pourheidar, Maryam

    2014-01-01

    We investigated the effects of insulin and honey as antioxidants to prevent the hippocampal cell death in streptozotocin-induced diabetic rats. We selected sixty Wister rats (5 groups of 12 animals each), including the control group (C), and four diabetic groups (control (D) and 3 groups treated with insulin (I), honey (H), and insulin plus honey (I + H)). Diabetes was induced by streptozotocin injection (IP, 60 mg/kg). Six weeks after the induction of diabetes, the group I received insulin (3-4 U/kg/day, SC), group H received honey (5 mg/kg/day, IP), and group I + H received a combination of the above at the same dose. Groups C and D received normal saline. Two weeks after treatment, rats were sacrificed and the hippocampus was extracted. Neuronal cell death in the hippocampal region was examined using trypan blue assay, "H & E" staining, and TUNEL assay. Cell viability assessment showed significantly lower number of living cells in group D than in group C. Besides, the mean number of living cells was significantly higher in group I, H, and I + H compared to group D. Therefore, it can be concluded that the treatment of the diabetic rats with insulin, honey, and a combination of insulin and honey can prevent neuronal cell death in different hippocampal areas of the studied samples.

  15. Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats.

    PubMed

    Prasath, Gopalan Sriram; Sundaram, Chinnakrishnan Shanmuga; Subramanian, Sorimuthu Pillai

    2013-10-01

    Persistent hyperglycemia is associated with chronic oxidative stress which contributes to the development and progression of diabetes-associated complications. The sensitivity of pancreatic β-cells to oxidative stress has been attributed to their low content of antioxidants compared with other tissues. Bioactive compounds with potent antidiabetic properties have been shown to ameliorate hyperglycemia mediated oxidative stress. Recently, we have reported that oral administration of fisetin (10 mg/Kg b.w.), a bioflavonoid found to be present in strawberries, persimmon, to STZ-induced experimental diabetic rats significantly improved normoglycemia. The present study was aimed to evaluate the antioxidant potential of fisetin in both in vitro and in vivo. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Fisetin was administered orally for 30 days. At the end of the study, all animals were killed. Blood samples were collected for the biochemical estimations. The antioxidant status was evaluated. Histological examinations were performed on pancreatic tissues. Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin. The treatment also improved the antioxidant status in pancreas as well as plasma of diabetic rats indicating the antioxidant potential of fisetin. In addition, the results of DPPH and ABTS assays substantiate the free radical scavenging activity of fisetin. Histological studies of the pancreas also evidenced the tissue protective nature of fisetin. It is concluded that, fisetin possesses antioxidant and anti-inflammatory property and may be considered as an adjunct for the treatment of diabetes.

  16. Methylene blue improves streptozotocin-induced memory deficit by restoring mitochondrial function in rats.

    PubMed

    Li, Lei; Qin, Li; Lu, Hai-Long; Li, Ping-Jing; Song, Yuan-Jian; Yang, Rong-Li

    2017-02-15

    The pathogenesis of Alzheimer's disease (AD) is well documented to involve mitochondrial dysfunction which causes subsequent oxidative stress and energy metabolic failure in hippocampus. Methylene blue (MB) has been implicated to be neuroprotective in a variety of neurodegenerative diseases by restoring mitochondrial function. The present work was to examine if MB was able to improve streptozotocin (STZ)-induced Alzheimer's type dementia in a rat model by attenuating mitochondrial dysfunction-derived oxidative stress and ATP synthesis decline. MB was administrated at a dose of 0.5mg/kg/day for consecutive 7days after bilateral STZ intracerebroventricular (ICV) injection (2.5mg/kg). We first demonstrated that MB treatment significantly ameliorated STZ-induced hippocampus-dependent memory loss in passive avoidance test. We also found that MB has the properties to preserve neuron survival and attenuate neuronal degeneration in hippocampus CA1 region after STZ injection. In addition, oxidative stress was subsequently evaluated by measuring the content of lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Importantly, results from our study showed a remarkable suppression of MB treatment on both MDA production and 4-HNE immunoactivity. Finally, energy metabolism in CA1 region was examined by detecting mitochondrial cytochrome c oxidase (CCO) activity and the resultant ATP production. Of significant interest, our result displayed a robust facilitation of MB on CCO activity and the consequent ATP synthesis. The current study indicates that MB may be a promising therapeutic agent targeting oxidative damage and ATP synthesis failure during AD progression.

  17. Antihyperglycemic effect of Fomitopsis pinicola extracts in streptozotocin-induced diabetic rats.

    PubMed

    Lee, Sang-Il; Kim, Jeong-Sook; Oh, Sung-Hee; Park, Kun-Young; Lee, Hyun-Goo; Kim, Soon-Dong

    2008-09-01

    The antihyperglycemic effect of a water extract (WE) and an alkali extract (AE) of the Fomitopsis pinicola fruit body was studied in streptozotocin (STZ)-induced diabetic rats. The STZ-induced diabetes mellitus (DM) control group lost a significant amount of body weight, whereas the normal control group (NC) gained weight; however, the DM-AE group gained a significant amount of weight, with weight gain approaching normal. Feed intake by the DM-AE group was also similar to the NC group. The liver and kidney weights per body weight increased with the STZ treatment; however, the weights were lower in the F. pinicola-treated groups and nearly normalized in the DM-AE group. The weights of the heart, lungs, and spleen were not influenced by the STZ treatment. Blood glucose levels of F. pinicola-treated DM groups were significantly lower than that of the DM group. In particular, STZ-induced hyperglycemia was remarkably inhibited by the AE-supplemented diet. Serum insulin levels were decreased with STZ injection; however, the decreased levels were almost restored to the NC level with F. pinicola supplementation. The increased serum fructosamine levels associated with hyperglycemia were decreased with the F. pinicola treatment. Cells of the pericentral regions were found to have significant swelling, and some necrotic cells were observed in the pancreas of DM animals; however, pancreatic tissue damage by STZ in the F. pinicola-supplemented diet groups was ameliorated. In this study, the AE from F. pinicola showed the highest antidiabetic effect among the treatments. These results indicate that constituents of F. pinicola may regulate hyperglycemia via either increased insulin secretion during recovery or the prevention of STZ-induced pancreatic damage. This is the first report of antihyperglycemic effects of F. pinicola in STZ-induced DM rats.

  18. Sodium tungstate attenuate oxidative stress in brain tissue of streptozotocin-induced diabetic rats.

    PubMed

    Nakhaee, Alireza; Bokaeian, Mohammad; Akbarzadeh, Azim; Hashemi, Mohammad

    2010-08-01

    High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms.

  19. Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats.

    PubMed

    Erejuwa, O O; Sulaiman, S A; Wahab, M S; Sirajudeen, K N S; Salleh, M S Md; Gurtu, S

    2010-09-01

    Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas.

  20. Prevention of Streptozotocin-Induced Diabetic Nephropathy by MG132: Possible Roles of Nrf2 and IκB

    PubMed Central

    Wang, Yangwei; Tan, Yi; Miao, Lining

    2017-01-01

    Our previous study showed that proteasomal inhibitor MG132 can prevent diabetic nephropathy (DN) along with upregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The present study was to investigate whether MG132 can prevent DN in wild-type and Nrf2-KO mice. Type 1 diabetes was induced in wild-type and Nrf2-KO mice by multiple low doses of streptozotocin. Two weeks after streptozotocin injection, both wild-type and Nrf2-KO mice were randomly divided into four groups: control, MG132, DM, and DM/MG132. MG132 (10 μg/kg/day) or vehicle was administered intraperitoneally for 4 months. Renal function, morphology, and biochemical changes were measured after 4-month treatment with MG132. MG132 treatment suppressed proteasomal activity in the two genotypes. In wild-type mice, MG132 attenuated diabetes-induced renal dysfunction, fibrosis, inflammation, and oxidative damage along with increased Nrf2 and IκB expression. Deletion of Nrf2 gene resulted in a partial, but significant attenuation of MG132 renal protection in Nrf2-KO mice compared with wild-type mice. MG132-increased IκB expression was not different between wild-type and Nrf2-KO mice. This work indicates that MG132 inhibits diabetes-increased proteasomal activity, resulting in Nrf2 and IκB upregulation and renal protection, which could be used as a strategy to prevent diabetic nephropathy. PMID:28373900

  1. A Comparison of Food-grade Folium mori (桑葉 Sāng Yè) Extract and 1-Deoxynojirimycin for Glycemic Control and Renal Function in Streptozotocin-induced Diabetic Rats

    PubMed Central

    Huang, Shiang-Suo; Yan, Yi-Hui; Ko, Chien-Hui; Chen, Ke-Ming; Lee, Shih-Chieh; Liu, Cheng-Tzu

    2014-01-01

    Folium mori (桑葉 Sāng Yè, leaf of Morus alba L.; FM) is known to possess hypoglycemic effects, and 1-deoxynojirimycin (1-DNJ) has been proposed as an important functional compound in FM. However, the hypoglycemic activity of purified 1-DNJ has been rarely studied. It is also not known how FM and 1-DNJ affect the development of DM nephropathy. This study compared the antidiabetic effect of a commercial FM product with that of purified 1-DNJ in streptozotocin-induced diabetic rats. Seven days after induction, the diabetic rats were gavaged with FM (1, 3, 10, and 30 mg/kg/day), 1-DNJ (30 mg/kg/day), or vehicle (distilled deionized water; 2 ml/kg/day) for 7 days. All doses of FM ameliorated fasting and post-prandial blood glucose concomitantly with an increase in peripheral and pancreatic levels of insulin and improved homeostasis model assessment (HOMA-IR) in diabetic rats in a dose-dependent manner. Increased thiobarbituric acid reactive substances (TBARS) and nitrate/nitrite levels in the kidney, liver, and muscle of diabetic rats were reversed by all doses of FM. The renal function of the diabetic rats was normalized by all doses of FM, while blood pressure changes were reversed by FM at doses of 3 mg/kg and above. Moreover, most of the above-mentioned parameters were improved by FM at doses of 3 mg/kg and above to a similar extent as that of 1-DNJ. The results showed superior antidiabetic potential of the commercial FM product for glycemic control and protection against the development of diabetic nephropathy. PMID:25161921

  2. Boron promotes streptozotocin-induced diabetic wound healing: roles in cell proliferation and migration, growth factor expression, and inflammation.

    PubMed

    Demirci, Selami; Doğan, Ayşegül; Aydın, Safa; Dülger, Esra Çikler; Şahin, Fikrettin

    2016-06-01

    Acute wounds do not generally require professional treatment modalities and heal in a predictable fashion, but chronic wounds are mainly accompanied with infection and prolonged inflammation, leading to healing impairments and continuous tissue degradation. Although a vast amount of products have been introduced in the market, claiming to provide a better optimization of local and systemic conditions of patients, they do not meet the expectations due to being expensive and not easily accessible, requiring wound care facilities, having patient-specific response, low efficiency, and severe side-effects. In this sense, developing new, safe, self-applicable, effective, and cheap wound care products with broad-range antimicrobial activity is still an attractive area of international research. In the present work, boron derivatives [boric acid and sodium pentaborate pentahydrate (NaB)] were evaluated for their antimicrobial activity, proliferation, migratory, angiogenesis, gene, and growth factor expression promoting effects on dermal cells in vitro. In addition, boron-containing hydrogel formulation was examined for its wound healing promoting potential using full-thickness wound model in streptozotocin-induced diabetic rats. The results revealed that while both boron compounds significantly increased proliferation, migration, vital growth factor, and gene expression levels of dermal cells along with displaying remarkable antimicrobial effects against bacteria, yeast, and fungi, NaB displayed greater antimicrobial properties as well as gene and growth factor expression inductive effects. Animal studies proved that NaB-containing gel formulation enhanced wound healing rate of diabetic animals and histopathological scores. Overall data suggest a potential promising therapeutic option for the management of chronic wounds but further studies are highly warranted to determine signaling pathways and target metabolisms in which boron is involved to elucidate the limitations

  3. Effects of parsley (Petroselinum crispum) extract versus glibornuride on the liver of streptozotocin-induced diabetic rats.

    PubMed

    Ozsoy-Sacan, Ozlem; Yanardag, Refiye; Orak, Haci; Ozgey, Yasemin; Yarat, Aysen; Tunali, Tugba

    2006-03-08

    Parsley (Petroselinum crispum) is one of the medicinal herbs used by diabetics in Turkey. The aim of this study is to investigate the effects of parsley (2g/kg) and glibornuride (5mg/kg) on the liver tissue of streptozotocin-induced diabetic rats. Swiss albino rats were divided into six groups: control; control+parsley; control+glibornuride; diabetic; diabetic+parsley; diabetic+glibornuride. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Parsley extract and glibornuride were given daily to both diabetic and control rats separately, until the end of the experiment, at day 42. The drugs were administered to one diabetic and one control group from days 14 to 42. On day 42, liver tissues were taken from each rat. In STZ-diabetic group, blood glucose levels, serum alkaline phosphatase activity, uric acid, sialic acid, sodium and potassium levels, liver lipid peroxidation (LPO), and non-enzymatic glycosylation (NEG) levels increased, while liver glutathione (GSH) levels and body weight decreased. In the diabetic group given parsley, blood glucose, serum alkaline phosphatase activity, sialic acid, uric acid, potassium and sodium levels, and liver LPO and NEG levels decreased, but GSH levels increased. The diabetic group, given glibornuride, blood glucose, serum alkaline phosphatase activity, serum sialic acid, uric acid, potassium, and liver NEG levels decreased, but liver LPO, GSH, serum sodium levels, and body weight increased. It was concluded that probably, due to its antioxidant property, parsley extract has a protective effect comparable to glibornuride against hepatotoxicity caused by diabetes.

  4. Decrease of FGF receptor (FGFR) and interstitial fibrosis in the kidney of streptozotocin-induced diabetic rats.

    PubMed

    Cheng, M F; Chen, L J; Wang, M C; Hsu, C T; Cheng, J T

    2014-01-01

    Fibrosis is the final disorder of end-stage renal disease. Activation of fibroblast growth factor (FGF) 23-klotho axis could suppress renal fibrosis in mice. Also, a marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats). However, relation of FGF in renal fibrosis remained unclear. This study was aimed to screen the effect of hyperglycemia on FGF receptor (FGFR) and fibrosis in kidney of rats with diabetic nephropathy and investigate this potential mechanism in cultured Madin-Darby Canine Kidney (MDCK) epithelial cells. STZ rats were used to treat with insulin or phloridzin at the dose sufficient to correct hyperglycemia for understanding the changes of renal dysfunction. The cultured MDCK cells were also used to treat with high glucose, hydrogen peroxide, or tiron in addition to transfection of siRNA to silence the klotho. Both insulin and phloridzin reversed fibrosis and FGFR expressions in kidney of STZ rats. It was confirmed in high glucose-exposed MDCK cells. However, klotho failed to modify the level of FGFR in MDCK cells. Meanwhile, FGFR was restored by tiron in MDCK cells and in diabetic rats without changing blood glucose. In conclusion, interstitial fibrosis and decreased FGFR expression are observed in the kidney of diabetic rats. This change is reversed by tiron without the correction of blood glucose. Also, klotho has no effect on expression of FGFR. Thus, decrease of oxidative stress is useful for the recovery of FGFR expression and improvement of renal fibrosis in type-1 like diabetic rats.

  5. Cholinergic and GABAergic receptor functional deficit in the hippocampus of insulin-induced hypoglycemic and streptozotocin-induced diabetic rats.

    PubMed

    Sherin, A; Anu, J; Peeyush, K T; Smijin, S; Anitha, M; Roshni, B T; Paulose, C S

    2012-01-27

    Neurotransmitter receptor functional regulation plays an important role in controlling the excitability and responsiveness of hippocampal neurons. Deregulation of its function is associated with seizure generation, motor deficits, and memory impairment. In the present study we investigated the changes in hippocampal cholinergic and GABA receptor binding and gene expression in insulin-induced hypoglycemic and streptozotocin-induced diabetic rats. Expression of cholinergic enzymes; acetylcholine esterase (AChE) and choline acetyltransferase (ChAT) upregulated and downregulated, respectively, in diabetic group, which was further exacerbated by hypoglycemia. Total muscarinic receptor, muscarinic M1, and GABA maximal binding (B(max)) significantly decreased in hypoglycemic and diabetic rats. In hypoglycemic group, the B(max) showed further decline compared with diabetes. Muscarinic M3 receptor B(max) and gene expression upregulated in hypoglycemic and diabetic group. Alpha7 nicotinic acetylcholine receptor (α7 nAChR) expression significantly downregulated in hypoglycemic and diabetic rats. Gene expression of glutamate decarboxylase (GAD), GABAAα1, and GABAB in hypoglycemic and diabetic rats downregulated, with more significant decrease in hypoglycemic group. Present findings show altered cholinergic, muscarinic, nicotinic receptor expression and thereby function. Decreased GABA receptor expression is associated with decline in GABAergic neurotransmission. Thus cholinergic receptor dysfunction and decreased GABAergic neuroprotective inhibitory function in the hippocampus of hypoglycemic and diabetic rats account for the increased vulnerability of hippocampus predisposing to neuronal damage, which is suggested to contribute to cognitive impairment and memory deficit reported in hypoglycemia and diabetes. Also, recurrent hypoglycemia in diabetes exacerbates the hippocampal dysfunction induced by diabetes, which has clinical significance in diabetes therapy.

  6. Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats.

    PubMed

    Wang, Yanwen; Campbell, Tony; Perry, Benjamin; Beaurepaire, Cécile; Qin, Ling

    2011-02-01

    Hypoglycemic effects of berberine (BBR) have been reported in several studies in cell and animal models. However, the mechanisms of action are not fully understood. The present study was therefore aimed at determining the effect and underlying mechanisms of action of BBR on diabetes in a high-fat diet- and streptozotocin-induced diabetic rat model. Ninety male Sprague-Dawley rats, 150 to 170 g, were housed individually in cages. Two groups (n = 12 each) were fed the AIN-93G diet (normal control) and the same diet modified to contain 33% fat and 2% cholesterol (high-fat control), respectively. The third group (n = 66) was fed the high-fat diet and injected intraperitoneally 2 weeks later with 35 mg/kg body weight of streptozotocin in citrate buffer (pH 4.5). The rats in both control groups were injected with the vehicle. After 12 days, rats with semifasting (5 hours) blood glucose levels between 14 and 25 mmol/L were divided into 4 groups (n = 12 each) and treated with 0 (diabetic control), 50, 100, and 150 mg/kg/d of BBR for 6 weeks while continuing on the high-fat diet. Hypoglycemic effects of BBR were consistently demonstrated by semifasting and fasting blood glucose levels, and insulin-sensitizing effects were seen during oral glucose tolerance testing. Berberine also reduced food intake while having no effect on body weight in diabetic rats. No effect of BBR was observed on plasma levels of insulin, adipokines (leptin and adiponectin), or inflammatory cytokines (tumor necrosis factor-α and C-reactive protein). Berberine did not affect the state of oxidative stress as assessed by the activity of superoxide dismutase and the concentrations of malondialdehyde and reduced and oxidized glutathione in the liver. These findings demonstrated the hypoglycemic and insulin-sensitizing capabilities of BBR, with the underlying mechanisms awaiting further investigation.

  7. The protective effects of DA-9801 (Dioscorea extract) on the peripheral nerves in streptozotocin-induced diabetic rats.

    PubMed

    Lee, Kyung Ae; Jin, Heung Yong; Baek, Hong Sun; Park, Tae Sun

    2013-01-01

    It has been reported that DA-9801, an extract mixture of Dioscorea japonica Thunb and Dioscorea nipponica Makino, produces a neurotrophic activity. Therefore, this study was conducted to examine the neuroprotective effects of DA-9801 in streptozotocin-induced diabetic rats. The experimental rats were divided into six groups: the control group, Group I (non-diabetic rats treated with DA-9801), Group II (diabetic, non-treated rats) and Groups III, IV, and V (diabetic rats treated with DA-9801 at doses of 10, 50 or 100 mg/kg/d). Following a 16-wk course of oral treatment with DA-9801, functional parameters (von Frey filament test, hot plate test), biochemical parameters (nerve growth factor (NGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6) were measured. An immunohistochemical staining was done to assess the neuroprotective effects of DA-9081 in the skin, sciatic nerve, gastric mucosa and renal cortex. In Week 8, pain was evoked by either tactile or thermal stimuli, whose threshold was significantly higher in Group III, IV and V than Group II. Western blot analysis showed a more significant increase in NGF and decrease in TNF-α and IL-6 in Group III, IV and V than in Group II (p<0.05). Moreover, following the treatment with DA-9801, a loss of intraepidermal nerve fibers (IENFs) was inhibited to a significant level in the skin, myelinated axonal fibers of the sciatic nerve and small nerve fibers innervating the gastric mucosa or renal cortex (p<0.05). Our results demonstrated that DA-9801 is a beneficial agent that protects the peripheral nerves in diabetic rats.

  8. Effect of natural honey from Ilam and metformin for improving glycemic control in streptozotocin-induced diabetic rats

    PubMed Central

    Nasrolahi, Ozra; Heidari, Reza; Rahmani, Fatima; Farokhi, Farah

    2012-01-01

    Objective(s): Diabetes mellitus is a public health problem and one of the five leading causes of death globally. In the present study, the effect of Metformin with natural honey was investigated on glycemia in the Streptozotocin-induced diabetic rats. Materials and Methods: Thirty Wistar male rats were randomly divided into six groups including C: non diabetic rats received distilled water, CH: non diabetic rats received honey, CD: diabetic rats administered with distilled water, DM: Metformin treated diabetic rats, DH: honey treated diabetic rats, and DMH: diabetic rats treated with a combination of Metformin and natural honey. Diabetes was induced by a single dose of Streptozotocin (65 mg/kg; i.p.). The animals were treated by oral gavage once daily for four weeks. At the end of the treatment period, the animals were sacrificed and their blood samples collected. Amount of glucose, triglyceride (TG), total cholesterol (TC), HDL cholesterol, LDL cholesterol, VLDL cholesterol, total bilirubin, and albumin were determined in serum. Results: Group CD: showed hyperglycemia (252.2±4.1 mg/dl), while level of blood glucose was significantly (p<0.01) reduced in groups DH (124.2±2.7 mg/dl), DM (108.0±3.4 mg/dl), and DMH (115.4±2.1 mg/dl). Honey in combination with Metformin significantly (p<0.01) reduced level of bilirubin but Metformin alone did not reduce bilirubin. Honey alone and in combination with Metformin also significantly reduced triglycerides, total cholesterol, LDL, VLDL and increased HDL, but Metformin did not reduced triglycerides and increased HDL. Conclusion: The results of the present study demonstrated that consuming natural honey with Metformin improves glycemic control and is more useful than consuming Metformin alone. The higher therapeutic effect of Ilam honey on lipid abnormalities than Tualang honey was also evident. PMID:25050251

  9. Endothelium-dependent relaxation and noradrenaline sensitivity in mesenteric resistance arteries of streptozotocin-induced diabetic rats.

    PubMed Central

    Taylor, P. D.; McCarthy, A. L.; Thomas, C. R.; Poston, L.

    1992-01-01

    1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries of control and streptozotocin-induced diabetic rats. 2. The diabetic rats demonstrated enhanced vascular sensitivity to noradrenaline compared with age-matched controls (pEC50 5.99 +/- 0.06 for diabetic rats, n = 25, versus 5.82 +/- 0.03 for controls, n = 45, P < 0.05). 3. Significant impairment of acetylcholine-induced relaxation was observed in arteries from the diabetic animals compared with controls (pEC50 6.81 +/- 0.17 for diabetic rats, n = 21, versus 7.54 +/- 0.17 for controls, n = 45, P < 0.001). 4. The difference between acetylcholine-induced relaxation in diabetic and control arteries remained in the presence of 10 microM indomethacin (pEC50 6.41 +/- 0.11 for diabetic rats, n = 16, versus 7.59 +/- 0.08 for controls, n = 20, P < 0.001). 5. The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 1 mM) produced profound inhibition of acetylcholine-induced relaxation in diabetic arteries but partial inhibition in controls. The incomplete inhibition of acetylcholine-induced relaxation by L-NMMA in the control arteries was the result of ineffective inhibition of nitric oxide synthase since an alternative inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM), led to similar inhibition to that seen in the diabetic arteries with L-NMMA. The endothelium-derived relaxing factor (EDRF)-mediated component of acetylcholine-induced relaxation determined by use of the nitric oxide synthase inhibitors was, therefore, apparently reduced in diabetic rats compared with control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1422588

  10. Down regulation of cerebellar serotonergic receptors in streptozotocin induced diabetic rats: Effect of pyridoxine and Aegle marmelose.

    PubMed

    Abraham, Pretty Mary; Paul, Jes; Paulose, C S

    2010-04-29

    Oxidative stress plays an important role in cerebellar damage caused by diabetes, leading to deterioration in glucose homeostasis causing metabolic disorders. The present study was carried out to find the effects of Aegle marmelose leaf extract and insulin alone and in combination with pyridoxine on the cerebellar 5-HT through 5-HT(2A) receptor subtype, gene expression studies on the status of antioxidants-superoxide dismutase (SOD), glutathione peroxidase (GPx), 5-HT(2A) and 5-HT transporter (5-HTT) and immunohistochemical studies in streptozotocin induced diabetic rats. 5-HT and 5-HT(2A) receptor binding parameters, B(max) and K(d), showed a significant decrease (p<0.001) in the cerebellum of diabetic rats compared to control. Gene expression studies of SOD, GPx, 5-HT(2A) and 5-HTT in cerebellum showed a significant down regulation (p<0.001) in diabetic rats compared to control. Pyridoxine treated alone and in combination with insulin, A. marmelose to diabetic rats reversed the B(max), K(d) of 5-HT, 5-HT(2A) and the gene expression of SOD, GPx, 5-HT(2A) and 5-HTT in cerebellum to near control. The gene expression of 5-HT(2A) and 5-HTT were confirmed by immunohistochemical studies. Also, the Rotarod test confirms the motor dysfunction and recovery by treatment. These data suggest the antioxidant and neuroprotective role of pyridoxine and A. marmelose through the up regulation of 5-HT through 5-HT(2A) receptor in diabetic rats. Our results suggest that pyridoxine treated alone and in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalizing diabetic related oxidative stress and neurodegeneration affecting the motor ability of an individual by serotonergic receptors through 5-HT(2A) function. This has clinical significance in the management of diabetes.

  11. Involvement of inducible nitric oxide synthase in hydroxyl radical-mediated lipid peroxidation in streptozotocin-induced diabetes

    PubMed Central

    Stadler, Krisztian; Bonini, Marcelo G.; Dallas, Shannon; Jiang, JinJie; Radi, Rafael; Mason, Ronald P.; Kadiiska, Maria B.

    2008-01-01

    Free radical production is implicated in the pathogenesis of diabetes mellitus, where several pathways and different mechanisms were suggested in the pathophysiology of the complications. In this study, we used electron paramagnetic resonance (EPR) spectroscopy combined with in vivo spin-trapping techniques to investigate the sources and mechanisms of free radical formation in streptozotocin-induced diabetic rats. Free radical production was directly detected in the diabetic bile, which correlated with lipid peroxidation in the liver and kidney. EPR spectra showed the trapping of a lipid-derived radical. Such radicals were demonstrated to be induced by hydroxyl radical through isotope labeling experiments. Multiple enzymes and metabolic pathways were examined as the potential source of the hydroxyl radicals using specific inhibitors. Neither xanthine oxidase, cytochrome P450s, the Fenton reaction, nor macrophage activation were required for the production of radical adducts. Interestingly, inducible nitric oxide synthase (apparently uncoupled) was identified as the major source of radical generation. The specific iNOS inhibitor 1400W as well as l-arginine pretreatment reduced the EPR signals to baseline levels, implicating peroxynitrite as the source of hydroxyl radical production. Applying immunological techniques, we localized iNOS overexpression in the liver and kidney of diabetic animals, which was closely correlated with the lipid radical generation and 4-hydroxynonenal-adducted protein formation, indicating lipid peroxidation. In addition, protein oxidation to protein free radicals occurred in the diabetic target organs. Taken together, our studies support inducible nitric oxide synthase as a significant source of EPR-detectable reactive intermediates, which leads to lipid peroxidation and may contribute to disease progression as well. PMID:18620046

  12. Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice.

    PubMed

    Li, Jinhua; Qu, Xinli; Bertram, John F

    2009-10-01

    Diabetic nephropathy is the leading cause of chronic renal failure. Myofibroblasts play a major role in the synthesis and secretion of extracellular matrix in diabetic renal fibrosis. Increasing evidence suggests that endothelial cells may undergo endothelial-myofibroblast transition under physiological and pathophysiological circumstances. Therefore, this study investigates whether endothelial-myofibroblast transition occurs and contributes to the development of diabetic renal interstitial fibrosis. Diabetes was induced by administration of streptozotocin to Tie2-Cre;LoxP-EGFP mice, an endothelial lineage-traceable mouse line generated by crossbreeding B6.Cg-Tg(Tek-cre)12F1v/J mice with B6.Cg-Tg(ACTB-Bgeo/GFP)21Lbe/J mice. The endothelial-myofibroblast transition was also studied in MMECs (a mouse pancreatic microvascular endothelial cell line) and primary cultures of CD31+/EYFP- (enhanced yellow fluorescent protein) endothelial cells isolated from adult normal alpha-smooth muscle actin promoter-driven-EYFP (alpha-SMA/EYFP) mouse kidneys. Confocal microscopy demonstrated that 10.4 +/- 4.2 and 23.5 +/- 7.4% of renal interstitial myofibroblasts (alpha-SMA+) in 1- and 6-month streptozotocin-induced diabetic kidneys were of endothelial origin (EGFP+/alpha-SMA+ cells), compared with just 0.2 +/- 0.1% of myofibroblasts in vehicle-treated Tie2-Cre;LoxP-EGFP mice (P < 0.01). Confocal microscopy and real-time PCR showed that transforming growth factor (TGF)-beta1 induced de novo expression of alpha-SMA and loss of expression of VE-cadherin and CD31 in MMECs and primary cultures of renal endothelial cells in a time- and dose-dependent fashion. These findings demonstrate that the endothelial-myofibroblast transition occurs and contributes to the early development and progression of diabetic renal interstitial fibrosis and suggest that the endothelial-myofibroblast transition may be a therapeutic target.

  13. Potent antihyperglycemic and hypoglycemic effect of Tamarix articulata Vahl. in normal and streptozotocin-induced diabetic rats.

    PubMed

    Hebi, Morad; Farid, Omra; Ajebli, Mohammed; Eddouks, Mohamed

    2017-03-01

    The purpose of this study was to investigate the effect of a single dose and daily oral administration for seven days of the aerial part aqueous extract (A.P.A.E) of Tamarix articulata Vahl. (T. articulata) (5mg/kg) on blood glucose levels in both normal and streptozotocin-induced diabetic rats (STZ). Single oral administration of T. articulata A.P.A.E reduced blood glucose levels 6h after administration in normal rats (p<0.0001) and STZ diabetic rats (p<0.001). Furthermore, blood glucose levels were decreased in both normal (p<0.05) and STZ diabetic rats (p<0.0001) after seven days of treatment. Moreover, no significant changes in body weight in normal and STZ rats were shown. According to the oral glucose tolerance test, the aqueous extract of T. articulata (5mg/kg) was shown to prevent significantly the increase on blood glucose levels in both normal and diabetic treated rats 30min, 60min and 120min after glucose administration when compared to the control group. Additionally, histopathological analysis revealed the beneficial effect of T. articulata on pancreas and liver. Finally, the antioxydant activity of the aqueous extract of Tamarix articulata was evaluated by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH). Tamarix articulata revealed inhibitory concentrations of 50% of free radicals (IC50) of 203.15μg/ml. In contrast, the synthetic antioxidant butylhydroxytoluene (BHT) has showed an IC50 equal to 13.71μg/ml. In conclusion, this study demonstrates antihyperglycemic, hypoglycemic and antioxidant effects of T. articulata in severe diabetic state thus warrants further investigation on its major compounds as well as mechanistic studies.

  14. Effects of angiotensin-converting enzyme inhibitor, captopril, on bone of mice with streptozotocin-induced type 1 diabetes.

    PubMed

    Diao, Teng-Yue; Pan, Hai; Gu, Sa-Sa; Chen, Xi; Zhang, Fang-Yi; Wong, Man-Sau; Zhang, Yan

    2014-05-01

    There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin-angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.

  15. Curcumol Promotes Vascular Endothelial Growth Factor (VEGF)-Mediated Diabetic Wound Healing in Streptozotocin-Induced Hyperglycemic Rats

    PubMed Central

    Zhou, Jie; Ni, Maowei; Liu, Xia; Ren, Zeming; Zheng, Zhiguo

    2017-01-01

    Background Wound healing in chronic diabetic mellitus is mainly associated with the management of angiogenesis. The angiogenic mechanism of vascular endothelial growth factor (VEGF) has been widely studied in the context of diabetic ulcers. The aim of this study was to investigate the wound-healing potential of curcumol in streptozotocin-induced diabetic rats. Material/Methods Sixty male SD (Sprague Dawley) rats were purchased and randomly assigned into four groups: a control group and a model group treated with blank ointment, a high-dose curcumol group, and a low-dose curcumol group. The number of animals in each group was 15. Diabetes was induced by an intraperitoneal injection of streptozotocin. Two cutaneous wounds were incised at the dorsal region of all the experimental animals. Wound healing was assessed for all animal groups by observing the rate of wound closure. The expression of VEGF at the wound sites was studied by immunohistochemical staining to evaluate the vascular endothelial cell reaction. VEGF protein and related mRNA levels were analyzed by Western blotting and RT-PCR (reverse transcription-polymerase chain reaction). Results Curcumol treatment significantly increased the rates of wound closure in treated animals, and hence wound healing was drastically enhanced for treatment groups compared to control groups. Histological observations and related mRNA and protein levels showed a higher VEGF expression in the treatment groups. Conclusions Our analyses clearly suggested that the observed enhancement in wound healing as a result of curcumol administration was attributable to VEGF-mediated angiogenesis. PMID:28138126

  16. Beneficial effects of an Andrographis paniculata extract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats.

    PubMed

    Thakur, Ajit Kumar; Rai, Geeta; Chatterjee, Shyam Sunder; Kumar, Vikas

    2016-09-01

    Context Andrographolide containing Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts is often used for treatments of diabetes and other inflammatory disorders commonly accompanying cognitive and other psychiatric disorders. Objective To compare the efficacies of a standardised A. paniculata extract (AP) and pure andrographolide on cognitive functions, oxidative stress and cholinergic function in diabetic rats. Materials and methods Streptozotocin-induced diabetic Charles Foster albino rats treated orally with a hydro-methanolic A. paniculata leaf extract (50, 100 and 200 mg/kg/day), or with pure andrographolide (15, 30 and 60 mg/kg/day) for 10 consecutive days, were subjected to Morris water maze test. After the test, acetylcholinesterase, superoxide dismutase (SOD), and catalase (CAT) activities and lipid peroxidation (LPO) in brain tissues were assessed. Results Acetylcholinesterase activity in pre-frontal cortex and hippocampus of diabetic rats was 2.1 and 2.6 times higher compared to nondiabetic rats. LPO was 1.6 times higher and decreased SOD (56.3%) and CAT (44.9%) activities in pre-frontal cortex of diabetic rats compared to nondiabetic rats. AP or andrographolide treatments dose dependently attenuated cognitive deficits, reduced acetylcholinesterase activity, oxidative stress, improved diabetic hyperglycemia and insulin deficiency. All observed effects of AP were quantitatively almost equal to those expected from its analytically quantified andrographolide content. Discussion and conclusion Reported observations are the very first ones suggesting beneficial effects of andrographolide against diabetes associated cognitive deficits, increased acetylcholinesterase activity and deteriorated antioxidative status. Efforts to exploit A. paniculata extracts enriched in andrographolide as preventive measures against such disorders can be warranted.

  17. Oleanolic acid prevents progression of streptozotocin induced diabetic nephropathy and protects renal microstructures in Sprague Dawley rats

    PubMed Central

    Dubey, Vishal K.; Patil, Chandragouda R.; Kamble, Sarika M.; Tidke, Priti S.; Patil, Kalpesh R.; Maniya, Pragnesh J.; Jadhav, Ramchandra B.; Patil, Sudha P.

    2013-01-01

    Objective: To study the effect of oleanolic acid (OA) on streptozotocin induced diabetic nephropathy in Sprague Dawley rats. Materials and Methods: Four weeks after intra-peritoneal injection of streptozotocin (STZ; 55 mg/kg), the rats with proteinuria were grouped as: Control (non-diabetic, treated orally with vehicle), diabetic control (treated orally with vehicle) and three diabetic groups receiving 20, 40 and 60 mg/kg/day oral doses of OA. At the end of 8 weeks, urine and serum samples from the rats were processed for determination of creatinine, BUN and GFR. The kidney samples were processed for determination of weight changes, oxidative stress related parameters like catalase, superoxide dismutase and reduced glutathione levels. A part of one kidney from each rat was used for transmission electron microscopy (TEM). Result: As evident in TEM, OA inhibited the nephropathy induced alterations in podocyte integrity, basement membrane thickness and spacing between the podocytes at 60 mg/kg dose. It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner. These findings conclusively demonstrate the efficacy of OA in diabetic nephropathy. Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA. However, OA is known to act through multiple mechanisms like inhibition of the generation of advanced glycation end products and improving the insulin secretion. These mechanisms might have contributed to its efficacy. Conclusion: These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity. PMID:23662024

  18. Evaluation of anti-diabetic activity of AHPL/AYTAB/0513 tablet in streptozotocin induced diabetes in rats

    PubMed Central

    Nipanikar, Sanjay U.; Chitlange, Soham S.; Nagore, Dheeraj

    2017-01-01

    Background: Diabetes is a chronic, progressive disease associated with several complications leading to significant mortality and morbidity. Limitations and drawbacks of the conventional treatment generate need for safer, effective complimentary therapies to prevent complications, and maintain normoglycemic status. Aim and Objectives: The aim of this study is to to evaluate antidiabetic activity of AHPL/AYTAB/0513 tablet alone, oral hypoglycemic agents (OHA[s]), and combination of AHPL/AYTAB/0513 tablet and OHA(s) in streptozotocin-induced diabetes in rats. Materials and Methods: Totally, ten groups of animals were studied comparatively to evaluate antidiabetic activity of AHPL/AYTAB/0513 tablet, OHA(s), and combination of AHPL/AYTAB/0513 tablet and OHA(s). Blood glucose level (BGL), lipid profile, serum creatinine, serum insulin level, and histopathological characteristics of pancreas were studied to evaluate the efficacy of various formulations. Histopathological examination of kidney and heart was carried out to assess the ability of various formulations in preventing complications of diabetes. Results: There was a significant decrease in mean BGL, serum triglycerides, serum total cholesterol, low-density lipoprotein (LDL), very LDL, and serum creatinine levels in all formulations groups. Significant increase in mean serum insulin level and high-density lipoprotein level was observed when compared to diabetic control (DC) group. Recovery of pancreatic beta cells and prevention of damage to heart and kidney cells was significant in all the formulation groups as compared to DC group. None of the formulations tested in nondiabetic rat showed hypoglycemia suggesting safety of all the formulations. Conclusion: AHPL/AYTAB/0513 tablet alone and in combination with OHA(s) can be effectively used in the management of diabetes mellitus. In addition, AHPL/AYTAB/0513 tablet alone and in combination with OHA(s) help in prevention of diabetic complications. As an adjuvant to

  19. Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice.

    PubMed

    Vujicic, Milica; Nikolic, Ivana; Kontogianni, Vassiliki G; Saksida, Tamara; Charisiadis, Pantelis; Vasic, Bobana; Stosic-Grujicic, Stanislava; Gerothanassis, Ioannis P; Tzakos, Andreas G; Stojanovic, Ivana

    2016-07-01

    Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MS(n) ). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4(+) and activated CD4(+) CD25(+) T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy.

  20. The effect of thiazolidin carboxylic acid (ThCA) on the redox equilibrium maintaining in the rat hepatocyte with streptozotocin-induced diabetes.

    PubMed

    Bartoc, R; Oancia, M; Pirvănescu, L

    1978-01-01

    The variation of the activities of glutathion peroxidase, glutathion reductase, glucose-6-phosphate dehydrogenase, as well as of the concentrations of lipid peroxides and -SH groups of nonproteic nature, was followed up in the hepatocyte of normal rats, of those with, streptozotocin-induced-diabetes, and of diabetic rats treated with thiazolidin carboxylic (ThCA) acid. Free peroxides and glutathion peroxidase were increased in the diabetic animals as against the normals, whereas glutathion reductase, glucose-6-phosphate dehydrogenase and the -SH groups of nonproteic nature had lower values. A return to normal of these parameters was noticed in the animals treated with ThCA.

  1. Influence of acute and chronic streptozotocin-induced diabetes on the rat tendon extracellular matrix and mechanical properties.

    PubMed

    Volper, Brent D; Huynh, Richard T; Arthur, Kathryn A; Noone, Joshua; Gordon, Benjamin D; Zacherle, Emily W; Munoz, Eduardo; Sørensen, Mikkel A; Svensson, René B; Broderick, Tom L; Magnusson, S Peter; Howden, Reuben; Hale, Taben M; Carroll, Chad C

    2015-11-01

    Diabetes is a major risk factor for tendinopathy, and tendon abnormalities are common in diabetic patients. The purpose of the present study was to evaluate the effect of streptozotocin (60 mg/kg)-induced diabetes and insulin therapy on tendon mechanical and cellular properties. Sprague-Dawley rats (n = 40) were divided into the following four groups: nondiabetic (control), 1 wk of diabetes (acute), 10 wk of diabetes (chronic), and 10 wk of diabetes with insulin treatment (insulin). After 10 wk, Achilles tendon and tail fascicle mechanical properties were similar between groups (P > 0.05). Cell density in the Achilles tendon was greater in the chronic group compared with the control and acute groups (control group: 7.8 ± 0.5 cells/100 μm(2), acute group: 8.3 ± 0.4 cells/100 μm(2), chronic group: 10.9 ± 0.9 cells/100 μm(2), and insulin group: 9.2 ± 0.8 cells/100 μm(2), P < 0.05). The density of proliferating cells in the Achilles tendon was greater in the chronic group compared with all other groups (control group: 0.025 ± 0.009 cells/100 μm(2), acute group: 0.019 ± 0.005 cells/100 μm(2), chronic group: 0.067 ± 0.015, and insulin group: 0.004 ± 0.004 cells/100 μm(2), P < 0.05). Patellar tendon collagen content was ∼32% greater in the chronic and acute groups compared with the control or insulin groups (control group: 681 ± 63 μg collagen/mg dry wt, acute group: 938 ± 21 μg collagen/mg dry wt, chronic: 951 ± 52 μg collagen/mg dry wt, and insulin group: 596 ± 84 μg collagen/mg dry wt, P < 0.05). In contrast, patellar tendon hydroxylysyl pyridinoline cross linking and collagen fibril organization were unchanged by diabetes or insulin (P > 0.05). Our findings suggest that 10 wk of streptozotocin-induced diabetes does not alter rat tendon mechanical properties even with an increase in collagen content. Future studies could attempt to further address the mechanisms contributing to the increase in tendon problems noted in diabetic patients

  2. Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats

    PubMed Central

    Abdul Nasir, Nurul Alimah; Agarwal, Renu; Sheikh Abdul Kadir, Siti Hamimah; Vasudevan, Sushil; Tripathy, Minaketan; Iezhitsa, Igor; Mohammad Daher, Aqil; Ibrahim, Mohd Ikraam; Mohd Ismail, Nafeeza

    2017-01-01

    Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats. Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Diabetic rats were treated with vehicle (DV) or tocotrienol (DT). A third group consists of normal, non-diabetic rats were treated with vehicle (NV). All treatments were given topically, bilaterally, twice daily for 8 weeks with weekly slit lamp monitoring. Subsequently, rats were euthanized and lenses were subjected to estimation of polyol accumulation, oxidative-nitrosative stress, NFκB activation, iNOS expression, ATP levels, ATPase activities, calpain activity and total protein levels. Cataract progression was delayed from the fifth week onwards in DT with lower mean of cataract stages compared to DV group (p<0.01) despite persistent hyperglycemia. Reduced cataractogenesis in DT group was accompanied with lower aldose reductase activity and sorbitol level compared to DV group (p<0.01). DT group also showed reduced NFκB activation, lower iNOS expression and reduced oxidative-nitrosative stress compared to DV group. Lenticular ATP and ATPase and calpain 2 activities in DT group were restored to normal. Consequently, soluble to insoluble protein ratio in DT group was higher compared to DV (p<0.05). In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase

  3. The effects of voluntary exercise and prazosin on capillary rarefaction and metabolism in streptozotocin-induced diabetic male rats.

    PubMed

    Dunford, Emily C; Leclair, Erwan; Aiken, Julian; Mandel, Erin R; Haas, Tara L; Birot, Olivier; Riddell, Michael C

    2017-03-01

    reduces both skeletal muscle mass and muscle capillarization. These muscle-specific features of diabetes may, in turn, compromise insulin sensitivity and glucose control. Using a model of streptozotocin-induced diabetes, we show the vascular complications linked with disease and how chronic exposure to exercise and prazosin (an α1-adrenergic antagonist) can reduce these complications and improve glycemic control.

  4. Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats.

    PubMed

    Abdul Nasir, Nurul Alimah; Agarwal, Renu; Sheikh Abdul Kadir, Siti Hamimah; Vasudevan, Sushil; Tripathy, Minaketan; Iezhitsa, Igor; Mohammad Daher, Aqil; Ibrahim, Mohd Ikraam; Mohd Ismail, Nafeeza

    2017-01-01

    Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats. Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Diabetic rats were treated with vehicle (DV) or tocotrienol (DT). A third group consists of normal, non-diabetic rats were treated with vehicle (NV). All treatments were given topically, bilaterally, twice daily for 8 weeks with weekly slit lamp monitoring. Subsequently, rats were euthanized and lenses were subjected to estimation of polyol accumulation, oxidative-nitrosative stress, NFκB activation, iNOS expression, ATP levels, ATPase activities, calpain activity and total protein levels. Cataract progression was delayed from the fifth week onwards in DT with lower mean of cataract stages compared to DV group (p<0.01) despite persistent hyperglycemia. Reduced cataractogenesis in DT group was accompanied with lower aldose reductase activity and sorbitol level compared to DV group (p<0.01). DT group also showed reduced NFκB activation, lower iNOS expression and reduced oxidative-nitrosative stress compared to DV group. Lenticular ATP and ATPase and calpain 2 activities in DT group were restored to normal. Consequently, soluble to insoluble protein ratio in DT group was higher compared to DV (p<0.05). In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase

  5. Proteomic analysis of gastrocnemius muscle in rats with streptozotocin-induced diabetes and chronically exposed to fluoride.

    PubMed

    Lima Leite, Aline; Gualiume Vaz Madureira Lobo, Janete; Barbosa da Silva Pereira, Heloísa Aparecida; Silva Fernandes, Mileni; Martini, Tatiani; Zucki, Fernanda; Sumida, Dóris Hissako; Rigalli, Alfredo; Buzalaf, Marília Afonso Rabelo

    2014-01-01

    Administration of high doses of fluoride (F) can alter glucose homeostasis and lead to insulin resistance (IR). This study determined the profile of protein expression in the gastrocnemius muscle of rats with streptozotocin-induced diabetes that were chronically exposed to F. Male Wistar rats (60 days old) were randomly distributed into two groups of 18 animals. In one group, diabetes was induced through the administration of streptozotocin. Each group (D-diabetic and ND-non-diabetic) was further divided into 3 subgroups each of which was exposed to a different F concentration via drinking water (0 ppm, 10 ppm or 50 ppm F, as NaF). After 22 days of treatment, the gastrocnemius muscle was collected and submitted to proteomic analysis (2D-PAGE followed by LC-MS/MS). Protein functions were classified by the GO biological process (ClueGO v2.0.7+Clupedia v1.0.8) and protein-protein interaction networks were constructed (PSICQUIC, Cytoscape). Quantitative intensity analysis of the proteomic data revealed differential expression of 75 spots for ND0 vs. D0, 76 for ND10 vs.D10, 58 spots for ND50 vs. D50, 52 spots for D0 vs. D10 and 38 spots for D0 vs. D50. The GO annotations with the most significant terms in the comparisons of ND0 vs. D0, ND10 vs. D10, ND50 vs. D50, D0 vs. D10 and D0 vs. D50, were muscle contraction, carbohydrate catabolic processes, generation of precursor metabolites and energy, NAD metabolic processes and gluconeogenesis, respectively. Analysis of subnetworks revealed that, in all comparisons, proteins with fold changes interacted with GLUT4. GLUT4 interacting proteins, such as MDH and the stress proteins HSPB8 and GRP78, exhibited decreased expression when D animals were exposed to F. The presence of the two stress proteins indicates an increase in IR, which might worsen diabetes. Future studies should evaluate whether diabetic animals treated with F have increased IR, as well as which molecular mechanisms are involved.

  6. Alterations in endothelium-dependent hyperpolarization and relaxation in mesenteric arteries from streptozotocin-induced diabetic rats

    PubMed Central

    Fukao, Mitsuhiro; Hattori, Yuichi; Kanno, Morio; Sakuma, Ichiro; Kitabatake, Akira

    1997-01-01

    The aim of this study was to determine whether endothelium-dependent hyperpolarization and relaxation are altered during experimental diabetes mellitus. Membrane potentials were recorded in mesenteric arteries from rats with streptozotocin-induced diabetes and age-matched controls. The resting membrane potentials were not significantly different between control and diabetic mesenteric arteries (−55.3±0.5 vs −55.6±0.4 mV). However, endothelium-dependent hyperpolarization produced by acetylcholine (ACh; 10−8–10−5 M) was significantly diminished in amplitude in diabetic arteries compared with that in controls (maximum −10.4±1.1 vs −17.2±0.8 mV). Furthermore, the hyperpolarizing responses of diabetic arteries were more transient. ACh-induced hyperpolarization observed in control and diabetic arteries remained unaltered even after treatment with 3×10−4 M NG-nitro-L-arginine (L-NOARG), 10−5 M indomethacin or 60 u ml−1 superoxide dismutase. Endothelium-dependent hyperpolarization with 10−6 M A23187, a calcium ionophore, was also decreased in diabetic arteries compared to controls (−8.3±1.4 vs −18.0±1.9 mV). However, endothelium-independent hyperpolarizing responses to 10−6 M pinacidil, a potassium channel opener, were similar in control and diabetic arteries (−20.0±1.4 vs −19.2±1.1 mV). The altered endothelium-dependent hyperpolarizations in diabetic arteries were almost completely prevented by insulin therapy. Endothelium-dependent relaxations by ACh in the presence of 10−4 M L-NOARG and 10−5 M indomethacin in diabetic arteries were also reduced and more transient compared to controls. These data indicate that endothelium-dependent hyperpolarization is reduced by diabetes, and this would, in part, account for the impaired endothelium-dependent relaxations in mesenteric arteries from diabetic rats. PMID:9257918

  7. Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz

    2014-01-01

    Diabetic encephalopathy is one of the severe complications in patients with diabetes mellitus. Findings indicate that saffron extract has antioxidant properties but its underlying beneficial effects on diabetic encephalopathy were unclear. In the present study, the protective activities of saffron were evaluated in diabetic encephalopathy. Saffron at 40 and 80 mg/kg significantly increased body weight and serum TNF-α and decreased blood glucose levels, glycosylated serum proteins, and serum advanced glycation endproducts (AGEs) levels. Furthermore, significant increase in HDL and decrease (P<0.05) in cholesterol, triglyceride, and LDL were observed after 28 days of treatment. At the end of experiments, the hippocampus tissue was used for determination of glutathione content (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Furthermore, saffron significantly increased GSH, SOD, and CAT but remarkably decreased cognitive deficit, serum TNF-α, and induced nitric oxide synthase (iNOS) activity in hippocampus tissue. Our findings indicated that saffron extract may reduce hyperglycemia and hyperlipidemia risk and also reduce the oxidative stress in diabetic encephalopathy rats. This study suggested that saffron extract might be a promising candidate for the improvement of chemically induced diabetes and its complications.

  8. Modulation of Glucose Metabolism by Balanced Deep-Sea Water Ameliorates Hyperglycemia and Pancreatic Function in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Ha, Byung Geun; Park, Jung-Eun; Shin, Eun Ji; Shon, Yun Hee

    2014-01-01

    The aim of this study was to determine the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in streptozotocin (STZ)-induced diabetic mice. BDSW was prepared by mixing DSW mineral extracts and desalinated water to yield a final hardness of 1000–4000 ppm. Male ICR mice were assigned to 6 groups; mice in each group were given tap water (normal and STZ diabetic groups) or STZ with BDSW of varying hardness (0, 1000, 2000, and 4000 ppm) for 4 weeks. The STZ with BDSW group exhibited lowered fasting plasma glucose levels than the STZ-induced diabetic group. Oral glucose tolerance tests showed that BDSW improves impaired glucose tolerance in STZ-induced diabetic mice. Histopathological evaluation of the pancreas showed that BDSW restores the morphology of the pancreatic islets of Langerhans and increases the secretion of insulin in STZ-induced diabetic mice. Quantitative real-time PCR assay revealed that the expression of hepatic genes involved in gluconeogenesis, glucose oxidation, and glycogenolysis was suppressed, while the expression of the genes involved in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in the STZ with BDSW group. BDSW stimulated PI3-K, AMPK, and mTOR pathway-mediated glucose uptake in C2C12 myotubes. BDSW increased AMPK phosphorylation in C2C12 myotubes and improved impaired AMPK phosphorylation in the muscles of STZ-induced diabetic mice. Taken together, these results suggest that BDSW is a potential anti-diabetic agent, owing to its ability to suppress hyperglycemia and improve glucose intolerance by modulating glucose metabolism, recovering pancreatic islets of Langerhans and increasing glucose uptake. PMID:25013896

  9. Ameliorative Effect of Saffron Aqueous Extract on Hyperglycemia, Hyperlipidemia, and Oxidative Stress on Diabetic Encephalopathy in Streptozotocin Induced Experimental Diabetes Mellitus

    PubMed Central

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz

    2014-01-01

    Diabetic encephalopathy is one of the severe complications in patients with diabetes mellitus. Findings indicate that saffron extract has antioxidant properties but its underlying beneficial effects on diabetic encephalopathy were unclear. In the present study, the protective activities of saffron were evaluated in diabetic encephalopathy. Saffron at 40 and 80 mg/kg significantly increased body weight and serum TNF-α and decreased blood glucose levels, glycosylated serum proteins, and serum advanced glycation endproducts (AGEs) levels. Furthermore, significant increase in HDL and decrease (P < 0.05) in cholesterol, triglyceride, and LDL were observed after 28 days of treatment. At the end of experiments, the hippocampus tissue was used for determination of glutathione content (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Furthermore, saffron significantly increased GSH, SOD, and CAT but remarkably decreased cognitive deficit, serum TNF-α, and induced nitric oxide synthase (iNOS) activity in hippocampus tissue. Our findings indicated that saffron extract may reduce hyperglycemia and hyperlipidemia risk and also reduce the oxidative stress in diabetic encephalopathy rats. This study suggested that saffron extract might be a promising candidate for the improvement of chemically induced diabetes and its complications. PMID:25114929

  10. [Structural alterations in pancreatic islets in streptozotocin-induced diabetic rats treated with of bioactive additive on the basis of Gymnema sylvestre].

    PubMed

    Snigur, G L; Samokhina, M P; Pisarev, V B; Spasov, A A; Bulanov, A E

    2008-01-01

    The structural alterations in pancreatic islets in streptozotocin-induced diabetic rats were studied after the administration of Gymnema sylvestre extract or its composition. Diabetes mellitus was modeled by daily injection of streptozotocin (20 mg/kg for 5 days) and single injection of 0.2 ml of complete Freund's adjuvant, Only the animals with the blood glucose level exceeding 15 mmol/l were included in the experiment. B- and A-endocrinocytes were demonstrated using immunocytochemistry. The proportions of the area of the pancreatic islets, occupied by B- and A-endocrinocytes, as well as the volume fraction of the pancreatic islets within the pancreas, were determined. In the model of streptozotocin-induced diabetes, the part of the total islet area occupied by B-endocrinocytes, was diminished in the pancreatic islets located in all the zones of the gland. Prophylactic administration of Gymnema sylvestre extract or its composition tended to restore the area occupied by B-endocrinocytes in the pancreatic islets. These results indicate the equal potency of the composition and extract of Gymnema sylvestre to induce the regeneration of B-endocrinocytes.

  11. Effect of coriander seed (Coriandrum sativum L.) ethanol extract on insulin release from pancreatic beta cells in streptozotocin-induced diabetic rats.

    PubMed

    Eidi, Maryam; Eidi, Akram; Saeidi, Ali; Molanaei, Saadat; Sadeghipour, Alireza; Bahar, Massih; Bahar, Kamal

    2009-03-01

    Coriander (Coriandrum sativum L.) is grown as a spice crop all over the world. The seeds have been used to treat indigestion, diabetes, rheumatism and pain in the joints. In the present study, an ethanol extract of the seeds was investigated for effects on insulin release from the pancreatic beta cells in streptozotocin-induced diabetic rats. Blood samples were drawn from the retro-orbital sinus before and 1.5, 3 and 5 h after administration of the seed extract. Serum glucose levels were determined by the glucose oxidase method. To determine the insulin releasing activity, after extract treatment the animals were anaesthetized by diethyl ether, the pancreas was excised, fixed in 10% formaldehyde and embedded in paraffin for sectioning. Pancreatic sections of 5 microm were processed for examination of insulin-releasing activity using an immunocytochemistry kit. The results showed that administration of the ethanol extract (200 and 250 mg/kg, i.p.) exhibited a significant reduction in serum glucose. Administration of streptozotocin decreased the number of beta cells with insulin secretory activity in comparison with intact rats, but treatment with the coriander seed extract (200 mg/kg) increased significantly the activity of the beta cells in comparison with the diabetic control rats. The extract decreased serum glucose in streptozotocin-induced diabetic rats and increased insulin release from the beta cells of the pancreas.

  12. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Cheng, Poh-Guat; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats. PMID:24348715

  13. Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.

    PubMed

    Li, Bing; Luo, Chen; Chowdhury, Subrata; Gao, Zu-Hua; Liu, Jun-Li

    2013-09-10

    Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis. Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis. We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition. To test this possibility, Parp1-/- and wild-type mice were injected with streptozotocin to induce diabetes. Separately, acute pancreatitis was induced with repeated injections of caerulein. Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level. The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation. In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion. Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells. In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.

  14. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Cheng, Poh-Guat; Phan, Chia-Wei; Sabaratnam, Vikineswary; Abdullah, Noorlidah; Abdulla, Mahmood Ameen; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats.

  15. Elevated levels of the serum endogenous inhibitor of nitric oxide synthase and metabolic control in rats with streptozotocin-induced diabetes.

    PubMed

    Xiong, Yan; Fu, Yun-feng; Fu, Si-hai; Zhou, Hong-hao

    2003-08-01

    This study was designed to determine the relationship between elevated levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and metabolic control in rats with streptozotocin-induced diabetes. Serum levels of ADMA were measured by high-performance liquid chromatography at 8 weeks after diabetes was induced. Endothelium-dependent relaxation to acetylcholine was tested in aortic rings from nondiabetic age-matched control, untreated diabetic, and insulin-treated diabetic rats to evaluate endothelial function. Serum concentrations of glucose, glycosylated serum protein, and malondialdehyde were examined to estimate metabolic control. Serum levels of ADMA increased dramatically in untreated diabetic rats compared with control rats. This elevation in ADMA levels was accompanied by impairment of the endothelium-dependent relaxation response to acetylcholine in aortic rings. Long-term insulin treatment not only prevented the elevation of serum ADMA levels, but also improved the impairment of endothelium-dependent relaxation in diabetic rats. Serum levels of glucose, glycosylated serum protein, and malondialdehyde were significantly increased in parallel with the elevation of ADMA in untreated diabetic rats compared with control rats. These parameters were normalized after diabetic rats received insulin treatment for 8 weeks. These results provide the first evidence that an elevation in the concentration of ADMA in rats with streptozotocin-induced diabetes is closely related to metabolic control of the disease.

  16. Sodium tungstate on some biochemical parameters of the parotid salivary gland of streptozotocin-induced diabetic rats: a short-term study.

    PubMed

    Leite, Mariana Ferreira; Nicolau, José

    2009-02-01

    Several studies have shown the antidiabetic properties of sodium tungstate. In this study, we evaluated some biochemical parameters of the parotid salivary gland of streptozotocin-induced diabetic rats treated with sodium tungstate solution (2 mg/ml). The studied groups were: untreated control (UC), treated control (TC), untreated diabetic (UD), and treated diabetic (TD). After 2 and 6 weeks of treatment, parotid gland was removed and total protein and sialic acid (free and total) concentration and amylase and peroxidase activities were determined. Data were compared by variance analysis and Tukey test (p < 0.05). The sodium tungstate treatment modestly decreased the glycemia of streptozotocin-induced diabetic rats. At week 2 of the study, parotid gland of diabetic rats presented a reduction of total protein concentration (55%) and an increase of amylase (120%) and peroxidase (160%) activities, free (150%) and total (170%) sialic acid concentration. No alteration in the evaluated parameters at week 6 of the study was observed. Sodium tungstate presented no significant effect in parotid gland. Our results suggest that diabetes causes initial modification in biochemical composition of parotid. However, this gland showed a recovery capacity after 6 week of the experimental time. Sodium tungstate has no effect in peripheral tissues, such as salivary glands.

  17. Investigating the effects of Citrullus colocynthis pulp on oxidative stress in testes and epididymis in streptozotocin-induced diabetic male rats

    PubMed Central

    Ostovan, Fereshteh; Gol, Ali; Javadi, Abdolreza

    2017-01-01

    Background: Diabetes mellitus is one of the most common metabolic diseases in humans, affecting 100 million people around the world. Objective: Investigating the effects of Citrullus colocynthis pulp on oxidant and antioxidant factors of testes and epididymis in streptozotocin-induced diabetic male rats. Materials and Methods: Thirty two male rats were divided into four groups (n=8) 1) N (normal) group, 2) N+C group, 3) D (diabetic) group and 4) D+C group. Groups N and D received normal saline 2 ml orally for two weeks and groups N+C and D+C received 10 mg/kg.bw Citrullus colocynthis pulp orally for two weeks. Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ) at 65 mg/kg. Results: D group had a significant increase in H2O2 (Hydrogen peroxide) and MDA (malondialdehyde) concentrations, and CAT (catalase) activity, and also a significant decrease in Peroxidase (POD) activity compared to N group. D+C group had a significant decrease in H2O2 and MDA concentrations and, CAT activity and significant increase in POD activity compared to D group. Conclusion: Citrullus colocynthis pulp in two weeks had beneficial effects on oxidants and antioxidants changes in reproductive system in streptozotocin-induced diabetic rats. PMID:28280799

  18. Pancreatic islet-specific overexpression of Reg3β protein induced the expression of pro-islet genes and protected the mice against streptozotocin-induced diabetes mellitus.

    PubMed

    Xiong, Xiaoquan; Wang, Xiao; Li, Bing; Chowdhury, Subrata; Lu, Yarong; Srikant, Coimbatore B; Ning, Guang; Liu, Jun-Li

    2011-04-01

    Reg family proteins have been implicated in islet β-cell proliferation, survival, and regeneration. The expression of Reg3β (pancreatitis-associated protein) is highly induced in experimental diabetes and acute pancreatitis, but its precise role has not been established. Through knockout studies, this protein was shown to be mitogenic, antiapoptotic, and anti-inflammatory in the liver and pancreatic acinars. To test whether it can promote islet cell growth or survival against experimental damage, we developed β-cell-specific overexpression using rat insulin I promoter, evaluated the changes in normal islet function, gene expression profile, and the response to streptozotocin-induced diabetes. Significant and specific overexpression of Reg3β was achieved in the pancreatic islets of RIP-I/Reg3β mice, which exhibited normal islet histology, β-cell mass, and in vivo and in vitro insulin secretion in response to high glucose yet were slightly hyperglycemic and low in islet GLUT2 level. Upon streptozotocin treatment, in contrast to wild-type littermates that became hyperglycemic in 3 days and lost 15% of their weight, RIP-I/Reg3β mice were significantly protected from hyperglycemia and weight loss. To identify specific targets affected by Reg3β overexpression, a whole genome DNA microarray on islet RNA isolated from the transgenic mice revealed more than 45 genes significantly either up- or downregulated. Among them, islet-protective osteopontin/SPP1 and acute responsive nuclear protein p8/NUPR1 were significantly induced, a result further confirmed by real-time PCR, Western blots, and immunohistochemistry. Our results suggest that Reg3β is unlikely an islet growth factor but a putative protector that prevents streptozotocin-induced damage by inducing the expression of specific genes.

  19. The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes

    PubMed Central

    Mohamed, Jamaludin; Shing, Saw Wuan; Md Idris, Muhd Hanis; Budin, Siti Balkis; Zainalabidin, Satirah

    2013-01-01

    OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days. RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients. PMID:24212844

  20. Effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rats.

    PubMed

    Zhang, Songyun; Li, Hongyan; Zhang, Lihui; Li, Jie; Wang, Ruiying; Wang, Mian

    2017-02-15

    Increasing evidence demonstrates an association between diabetes and hippocampal neuron damage. This study aimed to determine the effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits (GCLM and GCLC) in the hippocampus of streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. At 12weeks after streptozotocin injection, T1DM rats were randomly divided into 4 groups (n=15 each group) to receive no treatment (T1DM), saline (T1DM+saline), alpha-lipoic acid (T1DM+alpha-lipoic acid), and troxerutin (T1DM+troxerutin), respectively, for 6weeks. Meanwhile, 10 control animals (NC group) were assessed in parallel. Learning performance was evaluated by the Morris water maze. After treatment, hippocampi were collected for pathological examination by hematoxylin and eosin (H&E) staining. Next, hippocampal superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and glutathione (GSH) levels were assessed. Finally, glutamate cysteine ligase catalytic (GCLC) and glutamate cysteine ligase modifier (GCLM) subunit mRNA and protein levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Compared with T1DM and T1DM+saline groups, escape latency was overtly reduced in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Significantly increased GCLM and GCLC mRNA levels, GCLC protein amounts, SOD activity, and GSH levels, and reduced MDA amounts were observed in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. In T1DM and T1DM+saline groups, H&E staining showed less pyramidal cells in the hippocampus, with disorganized layers, karyopyknosis, decreased endochylema, and cavitation, effects relieved in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Troxerutin alleviates oxidative stress and promotes learning in streptozotocin-induced T1DM rats, a process involving GCLC expression.

  1. Rhinacanthus nasutus Improves the Levels of Liver Carbohydrate, Protein, Glycogen, and Liver Markers in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Visweswara Rao, Pasupuleti; Madhavi, K.; Dhananjaya Naidu, M.; Gan, Siew Hua

    2013-01-01

    The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200 mg/kg/day while glibenclamide was administered at 50 mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state. PMID:24204387

  2. Dried leaf extract of Olea europaea ameliorates islet-directed autoimmunity in mice.

    PubMed

    Cvjetićanin, Tamara; Miljković, Djordje; Stojanović, Ivana; Dekanski, Dragana; Stosić-Grujicić, Stanislava

    2010-05-01

    The health-promoting effects of various constituents of the olive tree (Olea europaea) are mainly associated with hypoglycaemic and insulin-sensitising activities and have been widely demonstrated in the metabolic syndrome and type 2 diabetes. However, their biological activity in autoimmune type 1 diabetes (T1D) is poorly characterised. Therefore, the influence of O. europaea-derived components present in dry olive leaf extract (DOLE) was examined in two established preclinical models of human T1D, which differ in some aspects of diabetogenesis: multiple low-dose streptozotocin-induced diabetes in susceptible C57BL/6 and CBA/H mouse strains; cyclophosphamide-accelerated diabetes in non-obese diabetic mice. In both T1D models, in vivo administration of DOLE significantly reduced clinical signs of diabetes (hyperglycaemia and body weight loss) and led to complete suppression of histopathological changes in pancreatic islets. In line with these, insulin expression and release were restored in DOLE-treated mice. Interestingly, inducible NO synthase expression and NO production were significantly elevated in peripheral tissues but were down-regulated within the local environment of the endocrine pancreas. This interference was reflected in NO-mediated suppression of T lymphocyte proliferation and lower production of the proinflammatory cytokines interferon-gamma, IL-17 and TNF-alpha in the spleen, with subsequent blockade of beta-cell destruction. The results suggest that DOLE interferes with development of autoimmune diabetes by down-regulating production of proinflammatory and cytotoxic mediators. Therefore, the potential use of a DOLE-enriched diet for prophylaxis/treatment of human T1D, and possibly other autoimmune diseases, is worthy of further investigation.

  3. Overexpression of intraislet ghrelin enhances β-cell proliferation after streptozotocin-induced β-cell injury in mice.

    PubMed

    Bando, Mika; Iwakura, Hiroshi; Ariyasu, Hiroyuki; Koyama, Hiroyuki; Hosoda, Kiminori; Adachi, Souichi; Nakao, Kazuwa; Kangawa, Kenji; Akamizu, Takashi

    2013-07-01

    Previously, we reported that exogenous administration of ghrelin ameliorates glucose metabolism in a neonate streptozotocin (STZ)-induced diabetic rat model through enhancement of β-cell proliferation. However, it was not clear whether the observed β-cell proliferation was a direct or indirect effect (e.g., via orexigenic or growth hormone-stimulated pathways) of ghrelin activity. Here, we aimed to investigate whether ghrelin directly impacts β-cell proliferation after STZ-induced injury in mice. Seven-week-old male rat insulin II promoter-ghrelin internal ribosomal sequence ghrelin O-acyltransferase transgenic (RIP-GG Tg) mice, which have elevated pancreatic ghrelin levels, but only minor changes in plasma ghrelin levels when fed a medium-chain triglyceride-rich diet, were treated with STZ. Then, serum insulin, pancreatic insulin mRNA expression, and islet histology were evaluated. We found that the serum insulin levels, but not blood glucose levels, of RIP-GG Tg mice were significantly ameliorated 14 days post-STZ treatment. Pancreatic insulin mRNA expression was significantly elevated in RIP-GG Tg mice, and β-cell numbers in islets were increased. Furthermore, the number of phospho-histone H3⁺ or Ki67⁺ proliferating β-cells was significantly elevated in RIP-GG Tg mice, whereas the apoptotic indexes within the islets, as determined by TUNEL assay, were not changed. These results indicate that ghrelin can directly stimulate β-cell proliferation in vivo after β-cell injury even without its orexigenic or GH-stimulating activities, although it did not have enough impact to normalize the glucose tolerance in adult mice.

  4. Effect of the hexane extract of Piper auritum on insulin release from β-cell and oxidative stress in streptozotocin-induced diabetic rat

    PubMed Central

    Gutierrez, Rosa Martha Perez

    2012-01-01

    Background: The large-leafed perennial plant Piper auritum known as Hoja Santa, is used for its leaves that because of their spicy aromatic scent and flavor have an important presence in Mexican cuisine, and in many regions, this plant is known for its therapeutic properties. Materials and Methods: In the present study, we investigated the effect of hexane, chloroform and methanol extracts from Piper auritum on cell culture system and the effect in streptozotocin-induced type 1 diabetic rats treated by 28 days on the physiological, metabolic parameters and oxidative stress. Results: The hexane extract of P. auritum (HS) treatment significantly reduced the intake of both food, water and body weight loss as well as levels of blood glucose, serum cholesterol, triglycerides and increase HDL-cholesterol. After 4-week administration of HS antioxidant enzyme as SOD, CAT, GSH, GPx in pancreas were determined. These enzyme increased significantly compared with those of the diabetic rats control and normal animals. For all estimated, the results of HS treated groups leading to a restoration of the defense mechanism. The treatment also improves pancreatic TBARS–reactive substance level and serum NO and iNOS. To determine the insulin releasing activity, after extract treatment the serum and pancreatic sections were processed for examination of insulin-releasing activity using an immunocytochemistry kit. The results showed that administration of the hexane extract (200 and 400 mg/kg) exhibited a significant increase in serum and pancreas tissue insulin. Administration of streptozotocin decreased the insulin secretory activity in comparison with intact rats, but treatment with the HS extract increased significantly the activity of the beta cells in comparison with the diabetic control rats. The extract decreased serum glucose in streptozotocin-induced diabetic rats and increased insulin release from the beta cells of the pancreas. In cultured RIN-5F cells, we examined whether

  5. Ensete superbum ameliorates renal dysfunction in experimental diabetes mellitus

    PubMed Central

    Sreekutty, MS; Mini, S

    2016-01-01

    Objective(s): Hyperglycemia mediated oxidative stress plays a key role in the pathogenesis of diabetic complications like nephropathy. In the present study, we evaluated the effect of ethanolic extract of Ensete superbum seeds (ESSE) on renal dysfunction and oxidative stress in streptozotocin-induced diabetic rats. Materials and Methods: Glucose, HbA1c, total protein, albumin, renal function markers (urea, uric acid and creatinine), and lipid peroxidation levels were evaluated. Renal enzymatic and non-enzymatic antioxidants were examined along with renal histopathological study. Results: ESSE (400 mg/kg BW t) administration reduced glucose and HbA1c, and improved serum total protein and albumin in diabetic rats. ESSE in diabetic rats recorded decrement in renal function markers and renal lipid peroxidation products along with significant increment in enzymatic and non-enzymatic antioxidants. Renal morphological abnormalities of diabetic rats were markedly ameliorated by E. superbum. Conclusion: These results suggest that the antioxidant effect of E. superbum could ameliorate oxidative stress and delay/prevent the progress of diabetic nephropathy in diabetes mellitus. PMID:27096072

  6. Antihypertriglyceridemia and Anti-Inflammatory Activities of Monascus-Fermented Dioscorea in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Shi, Yeu-Ching; Liao, Jiunn-Wang; Pan, Tzu-Ming

    2011-01-01

    The rice fermented by Monascus, called red mold rice (RMR), and has a long tradition in East Asia as a dietary staple. Monascus-fermented dioscorea called red mold dioscorea (RMD) contains various metabolites to perform the ability of reducing oxidative stress and anti-inflammatory response. We used Wistar rats and induced diabetes by injecting streptozotocin (STZ, 65 mg/kg i.p.). RMD was administered daily starting six weeks after disease onset. Throughout the experimental period, significantly (P < .05) lowered plasma glucose, triglyceride, cholesterol, free fatty acid and low density lipoprotein levels were observed in the RMD-treated groups. The RMD-treated diabetic rats showed higher activities of glutathione disulfide reductase, glutathione reductase, catalase and superoxide dismutase (P < .05) in the pancreas compared with the diabetic control rats. RMD also inhibited diabetes-induced elevation in the levels of interleukin (IL)-1β, IL-6, interferon-γ and tumor necrosis factor-α. Pancreatic β-cells damaged by STZ in the RMD supplemented groups were ameliorated. The results of this study clearly demonstrated that RMD possesses several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects, pancreatic β-cell protection and anti-inflammatory effects. Considering these observations, it appears that RMD may be a useful supplement to delay the development of diabetes and its complications. PMID:21716679

  7. Potent effects of the total saponins from Dioscorea nipponica Makino against streptozotocin-induced type 2 diabetes mellitus in rats.

    PubMed

    Yu, Hao; Zheng, Lingli; Xu, Lina; Yin, Lianhong; Lin, Yuan; Li, Hua; Liu, Kexin; Peng, Jinyong

    2015-02-01

    The aim of the present paper was to investigate the effects and possible mechanisms of the total saponins from Dioscorea nipponica Makino (TSDN) against type 2 diabetes mellitus. Streptozotocin (STZ) with high-fat diet induced type 2 diabetes mellitus (T2DM) rats were treated with TSDN. Some biochemical parameters, target proteins and genes were investigated. The results showed that TSDN decreased the levels of food/water intake, fasting blood glucose and serum lipid parameters, ameliorated oral glucose and insulin tolerance test levels, markedly increased body weight and serum insulin, reduced excess free radicals and affected ossification and renal protection. Histopathological examination indicated that TSDN increased liver glycogen, decreased the production of lipid vacuoles and lightened liver damage. Further investigation showed that TSDN down-regulated the protein expressions of NF-κB, GRP78, ATF6, eIF2 and the levels of MAPK phosphorylation and up-regulated the protein expressions of IRS-1, GLUT-4, p-Akt and p-AMPK. In addition, TSDN obviously decreased the gene expressions of TNF-a, IL-6, PEPCK, G6Pase, GSK-3β and GSK-3β activity, and increased the gene expressions of PFK, PK and GK activity. These findings show the anti-diabetic activity of total saponins from D. nipponica Makino, which should be developed as a new potent drug for treatment of diabetes mellitus in future.

  8. Peripheral nerve metabolism and zinc levels in streptozotocin induced diabetic rats. Effect of diets high in fish and corn oil

    SciTech Connect

    Burke, J.P.; Fenton, M.R. )

    1991-03-15

    This study was designed to assess the effects of diets high in fish and corn oil on peripheral nerve metabolism in streptozotocin (STZ) induced diabetic rats. A type I diabetic state was induced in female Sprague-Dawley rats by injection of STZ. Animals were divided into three dietary groups; normal rat chow, high corn oil diet and high fish oil diet. After 4 weeks animals were analyzed for nerve conduction velocity, bled and then sacrificed. Sciatic nerves were removed, processed and several biochemical parameters determined. Plasma zinc levels were elevated in the STZ normal chow group compared to non-diabetic controls. Both corn oil and fish oil diets tended to eliminate the rise in plasma zinc. Differences in subcellular distribution of zinc in sciatic nerves were also observed. Normal chow STZ animals displayed a 20% decrease in nerve conduction velocity compared to control. Dietary supplementation with either fish or corn oil seemed to ameliorate these effects. Biochemical analysis of Na{sup +}-K{sup +}-ATPase and protein kinase C revealed a decrease in activity in normal chow animals compared to control groups. Again, dietary intervention with either fish or corn oil seemed to return these activities back to normal. The results suggest a link between zinc metabolism and peripheral nerve metabolism which can be modified by dietary intervention.

  9. Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz; Farkhondeh, Tahereh

    2016-04-01

    Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

  10. Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity

    PubMed Central

    Wu, Jinzi; Yan, Liang-Jun

    2015-01-01

    Chronic hyperglycemia and the corresponding glucotoxicity are the main pathogenic mechanisms of diabetes and its complications. Streptozotocin (STZ)-induced diabetic animal models are useful platforms for the understanding of β cell glucotoxicity in diabetes. As diabetes induced by a single STZ injection is often referred to as type 1 diabetes that is caused by STZ’s partial destruction of pancreas, one question often being asked is whether the STZ type 1 diabetes animal model is a good model for studying the mitochondrial mechanisms of β cell glucotoxicity. In this mini review, we provide evidence garnered from the literature that the STZ type 1 diabetes is indeed a suitable model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity. Evidence presented includes: 1) continued β cell derangement is due to chronic hyperglycemia after STZ is completely eliminated out of the body; 2) STZ diabetes can be reversed by insulin treatment, which indicates that β cell responds to treatment and shows ability to regenerate; and 3) STZ diabetes can be ameliorated or alleviated by administration of phytochemicals. In addition, mechanisms of STZ action and fundamental gaps in understanding mitochondrial mechanisms of β cell dysfunction are also discussed. PMID:25897251

  11. Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats

    PubMed Central

    Zhou, Feng; Hui, Yu; Xin, Hua; Xu, Yong-De; Lei, Hong-En; Yang, Bi-Cheng; Guan, Rui-Li; Li, Meng; Hou, Jian-Quan; Xin, Zhong-Cheng

    2017-01-01

    This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg−1), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors. PMID:27345005

  12. Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats.

    PubMed

    Zhou, Feng; Hui, Yu; Xin, Hua; Xu, Yong-De; Lei, Hong-En; Yang, Bi-Cheng; Guan, Rui-Li; Li, Meng; Hou, Jian-Quan; Xin, Zhong-Cheng

    2017-01-01

    This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg-1 ), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors.

  13. The efficacy of Aesculus hippocastanum seeds on diabetic nephropathy in a streptozotocin-induced diabetic rat model.

    PubMed

    Elmas, Onur; Erbas, Oytun; Yigitturk, Gurkan

    2016-10-01

    Cytokines, such as transforming growth factor (TGF)-ß1, and increased oxidative stress are considered to be responsible for the development of diabetic nephropathy. We hypothesized that Aesculus hippocastanum (AH) seeds may have preventive effects on oxidative stress and TGF-β-related diabetic nephropathy in streptozotocin (STZ)-induced diabetic nephropathy in rats. Twenty-one male Sprague-Dawley albino rats were divided into three groups (n=7). Except for the control group, they all had diabetic nephropathy induced by an intraperitoneal injection of STZ. While the diabetes group did not receive any medication, the diabetes+AH group was given the medication for 4 weeks. After the experiment, analyses were performed to evaluate the glomerular area, severity of sclerosis, and fibronectin immunoexpression, as well as levels of malondialdehyde (MDA), TGF-β, blood urea nitrogen (BUN), blood glucose, creatinine, and proteinuria. It was found that glomerular area, severity of sclerosis, fibronectin immunoexpression, and levels of MDA, TGF-β, BUN, creatinine, and proteinuria were decreased in the diabetes+AH group. It is known that diabetic nephropathy is induced, to a large extent, by hyperglycemia. In the present study, AH extract ameliorated diabetic nephropathy without decrease in blood glucose levels. In the study, AH seeds showed beneficial effects on the functional properties of the kidney and microscopic improvements in diabetic nephropathy.

  14. Ursodeoxycholic Acid Attenuates Endoplasmic Reticulum Stress-Related Retinal Pericyte Loss in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Choi, Jeong A.; Koh, Jae-Young

    2017-01-01

    Loss of pericytes, an early hallmark of diabetic retinopathy (DR), results in breakdown of the blood-retinal barrier. Endoplasmic reticulum (ER) stress may be involved in this process. The purpose of this study was to examine the effects of ursodeoxycholic acid (UDCA), a known ameliorator of ER stress, on pericyte loss in DR of streptozotocin- (STZ-) induced diabetic mice. To assess the extent of DR, the integrity of retinal vessels and density of retinal capillaries in STZ-induced diabetic mice were evaluated. Additionally, induction of ER stress and the unfolded protein response (UPR) were assessed in diabetic mice and human retinal pericytes exposed to advanced glycation end products (AGE) or modified low-density lipoprotein (mLDL). Fluorescein dye leakage during angiography and retinal capillary density were improved in UDCA-treated diabetic mice, compared to the nontreated diabetic group. Among the UPR markers, those involved in the protein kinase-like ER kinase (PERK) pathway were increased, while UDCA attenuated UPR in STZ-induced diabetic mice as well as AGE- or mLDL-exposed retinal pericytes in culture. Consequently, vascular integrity was improved and pericyte loss reduced in the retina of STZ-induced diabetic mice. Our findings suggest that UDCA might be effective in protecting against DR. PMID:28127564

  15. Preventive Effects of the Chinese Herbal Medicine Prescription Tangkuei Decoction for Frigid Extremities on Sciatic Neuropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Liu, Pengsong; Bian, Yuanyuan; Zhang, Hong; Jia, Aiming

    2016-01-01

    Ischemia and hypoxia are important physiological changes in diabetic peripheral neuropathy (DPN). Chinese herbal medicine prescription Tangkuei Decoction for Frigid Extremities (TDFE) is useful for increasing blood flow. To help determine whether TDFE could protect the peripheral nerves of diabetic patients from the degeneration caused by high blood glucose, TDFE was administered to streptozotocin-induced diabetic rats for 6 or 12 weeks. Plantar thermal stimulation reaction time thresholds, sciatic nerve conduction velocities, and the levels of HIF-1α mRNA, HIF-1α protein, VEGF protein, and the endothelial marker vWF in sciatic nerves were measured at the end of the sixth and twelfth weeks. The thermal thresholds and sciatic nerve conduction velocities of the rats differed after 12 weeks, and the sciatic nerves of the diabetic rats that were given TDFE displayed higher levels of HIF-1α protein, VEGF protein, and HIF-1α mRNA than those of the diabetic model rats. The results at 6 weeks differed from those at 12 weeks. These results suggest that the early preventive application of TDFE effectively delayed the development of DPN and that TDFE increased HIF-1α mRNA levels in the sciatic nerves of diabetic rats through 12 weeks of treatment. PMID:27057201

  16. Effects of a standardized extract of Rheum turkestanicum Janischew root on diabetic changes in the kidney, liver and heart of streptozotocin-induced diabetic rats.

    PubMed

    Hosseini, Azar; Mollazadeh, Hamid; Amiri, Mohammad Sadegh; Sadeghnia, Hamid Reza; Ghorbani, Ahmad

    2017-02-01

    Numerus studies highlighted benefits of natural flavonoids in the management of diabetes. The present study was aimed to investigate the effects of a high flavonoids containing extract of Rheum turkestanicum on diabetic changes in different tissues. Male Wistar rats were divided into normal and streptozotocin-induced diabetic groups received saline or hydroalcoholic extract of R. turkestanicum root (100, 200 and 300mg/kg) through orogastric gavage for 4 weeks. Serum glucose, HbA1c, lipids, creatinine, uric acid, liver enzymes (alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase), and cardiac enzymes (lactate dehydrogenase and creatine phosphokinase) in diabetic control group were significantly higher compared to normal control group (p<0.001). The extract significantly reduced these factors, increased body weight, and improved both glucosurea and proteinuria. Lipid peroxidation was high in the liver of diabetic rats compared to normal rats (p<0.001) and reverted toward control values by R. turkestanicum. Also, the extract significantly protected the liver, kidney, and heart of diabetic rats against histopathological changes. In conclusion, R. turkestanicum inhibited the development of nephropathy, liver injury, and myocardial damage in diabetes by lowering the serum levels of glucose and lipids, and by inhibiting oxidative stress mediated lipid peroxidation.

  17. Effects of decompression on behavioral, electrophysiologic, and histomorphologic recovery in a chronic sciatic nerve compression model of streptozotocin-induced diabetic rats

    PubMed Central

    Wang, Ping-Hui; Yang, Cheng-Chang; Su, Wei-Ren; Wu, Po-Ting; Cheng, Shun-Chien; Jou, I-Ming

    2017-01-01

    Purpose To determine susceptibility to decompression surgery in diabetic and nondiabetic peripheral neuropathy using a chronic compression neuropathy model. Materials and methods Twenty-four streptozotocin-induced diabetic rats were randomly divided into three groups: group I, chronic compression of the left sciatic nerve for 4 weeks with decompression; group II, similar without decompression; and group III, sham exposing the sciatic nerve only. The other 24 nondiabetic rats were assigned to groups IV–VI, which received compression–decompression, compression, and the sham operation, respectively. Mixed-nerve-elicited somatosensory evoked potentials (M-SSEPs) and compound muscle action potentials (CMAPs) were measured to verify the compression neuropathy in the posttreatment follow-up. Behavioral observations in thermal hyperalgesia tests were quantified before electrophysiologic examinations. Treated and contralateral nerves were harvested for histomorphologic analysis. Results Chronic compression of sciatic nerve induced significant reduction of amplitude and increment of latency of M-SSEP and CMAP in both diabetic and nondiabetic rats. Diabetic group changes were more susceptible. Decompression surgery significantly improved both sensory and motor conduction, thermal hyperalgesia, and the mean myelin diameter of the rat sciatic nerve in both diabetic and nondiabetic groups. Near full recovery of motor and sensory function occurred in the nondiabetic rats, but not in the diabetic rats 8 weeks postdecompression. Conclusion Behavioral, electrophysiologic, and histomorphologic findings indicate that decompression surgery is effective in both diabetic and nondiabetic peripheral neuropathy. PMID:28360533

  18. Effect of recombinant α1-antitrypsin Fc-fused (AAT-Fc)protein on the inhibition of inflammatory cytokine production and streptozotocin-induced diabetes.

    PubMed

    Lee, Siyoung; Lee, Youngmin; Hong, Kwangwon; Hong, Jaewoo; Bae, Suyoung; Choi, Jida; Jhun, Hyunjhung; Kwak, Areum; Kim, Eunsom; Jo, Seunghyun; Dinarello, Charles A; Kim, Soohyun

    2013-05-20

    α1-Antitrypsin (AAT) is a member of the serine proteinase inhibitor family that impedes the enzymatic activity of serine proteinases, including human neutrophil elastase, cathepsin G and neutrophil proteinase 3. Here, we expressed recombinant AAT by fusing the intact AAT gene to the constant region of IgG1 to generate soluble recombinant AAT-Fc protein. The recombinant AAT-Fc protein was produced in Chinese hamster ovary (CHO) cells and purified using mini-protein A affinity chromatography. Recombinant AAT-Fc protein was tested for antiinflammatory function and AAT-Fc sufficiently suppressed tumor necrosis factor (TNF)-α-induced interleukin (IL)-6 in human peripheral blood mononuclear cells (PBMCs) and inhibited cytokine-induced TNFα by different cytokines in mouse macrophage Raw 264.7 cells. However, AAT-Fc failed to suppress lipopolysaccharide-induced cytokine production in both PBMCs and macrophages. In addition, our data showed that AAT-Fc blocks the development of hyperglycemia in a streptozotocin-induced mouse model of diabetes. Interestingly, we also found that plasma-derived AAT specifically inhibited the enzymatic activity of elastase but that AAT-Fc had no inhibitory effect on elastase activity.

  19. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet

    PubMed Central

    El-Zeftawy, Marwa; Taha, Nabil; Mandour, Abdel Wahab

    2016-01-01

    The black cumin (Nigella sativa) “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling. PMID:27579151

  20. A streptozotocin-induced diabetic neuropathic pain model for static or dynamic mechanical allodynia and vulvodynia: validation using topical and systemic gabapentin.

    PubMed

    Ali, Gowhar; Subhan, Fazal; Abbas, Muzaffar; Zeb, Jehan; Shahid, Muhammad; Sewell, Robert D E

    2015-11-01

    Neuropathic vulvodynia is a state of vulval discomfort characterized by a burning sensation, diffuse pain, pruritus or rawness with an acute or chronic onset. Diabetes mellitus may cause this type of vulvar pain in several ways, so this study was conducted to evaluate streptozotocin-induced diabetes as a neuropathic pain model for vulvodynia in female rats. The presence of streptozotocin (50 mg/kg i.p.)-induced diabetes was initially verified by disclosure of pancreatic tissue degeneration, blood glucose elevation and body weight loss 5-29 days after a single treatment. Dynamic (shortened paw withdrawal latency to light brushing) and static (diminished von Frey filament threshold pressure) mechanical allodynia was then confirmed on the plantar foot surface. Subsequently, both static and dynamic vulvodynia was detected by application of the paradigm to the vulval region. Systemic gabapentin (75 mg/kg, i.p.) and topical gabapentin (10 % gel) were finally tested against allodynia and vulvodynia. Topical gabapentin and the control gel vehicle significantly increased paw withdrawal threshold in the case of the static allodynia model and also paw withdrawal latency in the model for dynamic allodynia when compared with the streptozotocin-pretreated group. Likewise, in the case of static and dynamic vulvodynia, there was a significant antivulvodynia effect of systemic and topical gabapentin treatment. These outcomes substantiate the value of this model not only for allodynia but also for vulvodynia, and this was corroborated by the findings not only with systemic but also with topical gabapentin.

  1. Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

    NASA Astrophysics Data System (ADS)

    Bozkurt, Ozlem; Haman Bayari, Sevgi; Severcan, Mete; Krafft, Christoph; Popp, Jürgen; Severcan, Feride

    2012-07-01

    The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.

  2. Evening primrose oil treatment corrects reduced conduction velocity but not depletion of arachidonic acid in nerve from streptozotocin-induced diabetic rats.

    PubMed

    Kuruvilla, R; Peterson, R G; Kincaid, J C; Eichberg, J

    1998-09-01

    The effects of evening primrose oil (EPO) treatment, a source of gamma-linolenic acid, on the proportions of arachidonoyl-containing molecular species (ACMS) in sciatic nerve phosphatidylcholine and phosphatidylethanolamine were determined in conjunction with alterations in nerve conduction velocity. Normal and diabetic rats were either untreated or fed a dietary supplement containing isocalorically equivalent amounts of either EPO or corn oil for the duration of the experiment. After 8 weeks of streptozotocin-induced diabetes, nerve conduction velocity was reduced 16% and this deficit was prevented by either EPO or corn oil treatment. Neither EPO nor corn oil supplementation significantly increased the depressed proportions of ACMS. The level of the linoleoyl-containing molecular species, 16:0/18:2, was elevated in the phospholipids from untreated diabetic rats and was further increased by EPO treatment. These results are consistent with decreased activity of the delta6 desaturase that is required for arachidonic acid synthesis in vivo, but suggests that an accompanying deficit in the subsequent delta5 desaturase-catalyzed reaction may be rate-limiting. These findings indicate that maintenance of normal ACMS levels is not required for prevention of diminished nerve conduction velocity and suggest that other factors influenced by an altered polyunsaturated fatty acid pattern, such as metabolites of linoleic acid or gamma-linolenic acid other than arachidonic acid, the energy state of the nerve or the degree of membrane fluidity may contribute to impaired nerve conduction velocity in diabetic neuropathy.

  3. Octaphlorethol A: a potent α-glucosidase inhibitor isolated from Ishige foliacea shows an anti-hyperglycemic effect in mice with streptozotocin-induced diabetes.

    PubMed

    Lee, Seung-Hong; Kang, Sung-Myung; Ko, Seok-Chun; Moon, Sang-Ho; Jeon, Byong-Tae; Lee, Dae Ho; Jeon, You-Jin

    2014-10-01

    α-Glucosidase inhibitors are important agents for decreasing postprandial hyperglycemia. The current study examined the inhibitory effects of octaphlorethol A (OPA) isolated from Ishige foliacea, a brown alga, on α-glucosidase, and analyzed the inhibitor's binding modes using the crystal structure of α-glucosidase. The effects of OPA on postprandial blood glucose levels after meals were also investigated. The IC50 value of OPA against α-glucosidase was 0.11 mM, which is higher than that of the commercial inhibitor acarbose. For further insights, we predicted the 3D structure of α-glucosidase and used a docking algorithm to simulate binding between α-glucosidase and OPA. These molecular modeling studies were successful, and indicated that OPA interacts with Phe575, His600, Arg526, Met444, Asp542, Tyr605, Ser448, Asp203, Lys480, and Phe450. Furthermore, increases in postprandial blood glucose levels were significantly suppressed in the OPA-treated group compared with those in the streptozotocin-induced diabetic or normal mice. Additionally, the area under the curve was significantly reduced following OPA administration (907 versus 1034 mg h dL(-1)) in the diabetic mice, along with a delay in the absorption of dietary carbohydrates. Collectively, these results indicated that OPA is a potent inhibitor of α-glucosidase, and shows potential to be used as an anti-diabetic agent.

  4. Effects of Trigonella foenum-graecum (L.) on retinal oxidative stress, and proinflammatory and angiogenic molecular biomarkers in streptozotocin-induced diabetic rats.

    PubMed

    Gupta, Suresh Kumar; Kumar, Binit; Nag, Tapas Chandra; Srinivasan, B P; Srivastava, Sushma; Gaur, Shrikant; Saxena, Rohit

    2014-03-01

    The aim of the present study was to investigate the protective effects of Trigonella foenum-graecum Linn. (fenugreek) in Streptozotocin-induced diabetic rat retina. Fenugreek (100 and 200 mg/kg body weights) treatment was carried out for 24 weeks and evaluated for inflammatory [tumor necrosis factor (TNF)-α and interleukin (IL)-1β] and angiogenic [vascular endothelial growth factor (VEGF) and protein kinase C (PKC)-β] molecular biomarkers. Retinal oxidative stress was evaluated by estimating antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Fluorescein angiography was performed to detect retinal vascular leakage. Electron microscopy was performed to determine basement membrane thickness. In the present study, significant rises in the expressions of retinal inflammatory (TNF-α and IL-1β) and angiogenic (VEGF and PKC-β) molecular biomarkers were observed in diabetic retinae compared with normal retinae. However, fenugreek-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic molecular biomarkers. Moreover, results from the present study showed positive modulatory effects of fenugreek on retinal oxidative stress. Fluorescein angiograms and fundus photographs obtained from diabetic retinae showed retinal vascular leakage. On the other hand, fenugreek-treated retinae did not show vascular leakage. Further, thickened BM was recorded in diabetic retina compared with normal retinae. However, fenugreek-treated retinae showed relatively lesser thickening of capillary BM. In conclusion, it may be postulated that fenugreek has great potential in preventing diabetes-induced retinal degeneration in humans after regular consumption in the specified dosage.

  5. Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands

    PubMed Central

    Knaś, M.; Daniszewska, I.; Klimiuk, A.; Kołodziej, U.; Waszkiel, D.; Ładny, J. R.; Żendzian-Piotrowska, M.

    2016-01-01

    Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions. PMID:27478848

  6. Urinary excretion of water-soluble vitamins increases in streptozotocin-induced diabetic rats without decreases in liver or blood vitamin content.

    PubMed

    Imai, Eri; Sano, Mitsue; Fukuwatari, Tsutomu; Shibata, Katsumi

    2012-01-01

    It is thought that the contents of water-soluble vitamins in the body are generally low in diabetic patients because large amounts of vitamins are excreted into urine. However, this hypothesis has not been confirmed. To investigate this hypothesis, diabetes was induced in male Wistar rats (6 wk old) by streptozotocin treatment, and they were then given diets containing low, medium or sufficient vitamins for 70 d. The contents of 6 kinds of B-group vitamins, namely vitamin B₁, vitamin B₂, vitamin B₆, vitamin B₁₂, folate and biotin, were determined in the urine, blood and liver. No basic differences among the dietary vitamin contents were observed. The urinary excretion of vitamins was higher in diabetic rats than in control rats. The blood concentrations of vitamin B₁₂ and folate were lowered by diabetes, while, those of vitamin B₁, vitamin B₂, vitamin B₆, and biotin were not. All liver concentrations of vitamins were increased in diabetic rats above those in control rats. These results showed that streptozotocin-induced diabetes increased urinary excretion of water-soluble vitamins, though their blood and liver concentrations were essentially maintained in the rats.

  7. Defects in the Acquisition of Tumor-Killing Capability of CD8+ Cytotoxic T Cells in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Chen, Shu-Ching; Su, Yu-Chia; Lu, Ya-Ting; Ko, Patrick Chow-In; Chang, Pei-Yu; Lin, Hung-Ju; Ho, Hong-Nerng; Lai, Yo-Ping

    2014-01-01

    Emerging evidences have shown that diabetes mellitus not only raises risk but also heightens mortality rate of cancer. It is not clear, however, whether antitumor CD8+ cytotoxic T lymphocyte (CTL) response is down-modulated in diabetic hosts. We investigated the impact of hyperglycemia on CTLs' acquisition of tumor-killing capability by utilizing streptozotocin-induced diabetic (STZ-diabetic) mice. Murine diabetes was induced by intraperitoneal injection of STZ (200 mg/kg) in C57BL/6 mice, 2C-T cell receptor (TCR) transgenic and P14-TCR transgenic mice. The study found that, despite harboring intact proliferative capacity measured with CFSE labeling and MTT assay, STZ-diabetic CD8+ CTLs displayed impaired effector functions. After stimulation, STZ-diabetic CD8+ CTLs produced less perforin and TNFα assessed by intracellular staining, as well as expressed less CD103 protein. Furthermore, adoptive transfer of STZ-diabetic P14 CD8+ effector cells showed an insufficient recruitment to the B16.gp33 melanoma and inadequate production of perforin, granzyme B and TNFα determined by immunohistochemistry in the tumor milieu. As a result, STZ-diabetic CD8+ effector cells were neither able to eliminate tumor nor to improve survival of tumor-bearing mice. Taken together, our data suggest that CD8+ CTLs are crippled to infiltrate into tumors and thus fail to acquire tumor-killing capability in STZ-diabetic hosts. PMID:25390652

  8. Differential responses to blood pressure and oxidative stress in streptozotocin-induced diabetic Wistar-Kyoto rats and spontaneously hypertensive rats: effects of antioxidant (honey) treatment.

    PubMed

    Erejuwa, Omotayo O; Sulaiman, Siti A; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N S; Salleh, Md Salzihan Md; Gurtu, Sunil

    2011-01-01

    Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress.

  9. Alleviation of hyperglycemia and hyperlipidemia by Phyllanthus virgatus forst extract and its partially purified fraction in streptozotocin induced diabetic rats

    PubMed Central

    Hashim, Arshya; Khan, M. Salman; Ahmad, Saheem

    2014-01-01

    Since, we previously demonstrated that sequentially extracted methanolic fraction showed marked antioxidant and antidiabetic property in vitro, the present study was design to evaluate the beneficial effects of Phyllanthus virgatus methanolic extract and its partially purified fraction on hyperglycemia and hyperlipidemia in streptozotocin (STZ) induced diabetic rats. The plant extract was subjected to repeated thin layer chromatographic fractionation followed by GC-MS analysis of active fraction. TLC data illustrated the presence of six prominent bands and the prelimnary screening of these bands against α-amylase inhibitory activity showed that the band with Rf value 0.514 has marked inhibitory property (IC50, 48 µg/ml). The diabetic rats were treated for four weeks with methanolic extract of P. virgatus (50 and 10 mg/rat/day), partially isolated active fraction (0.5 and 0.1 mg/rat/day) and glibenclamide (0.1 mg/rat/day). The level of fasting blood glucose (FBG), hemoglobin, glycated hemoglobin (HbA1c) and insulin were significantly alleviated in plant extract and partially purified fraction treated group after 28 days of administration. Moreover, total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein cholesterol (HDL-C) were also markedly ameliorated in the entire treatment group, with a maximum restoration observed in group treated with partially purified fraction (0.5 mg/rat/day). The results demonstrate a strong antidiabetic and hypolipidemic impact of plant extract and its partially purified fraction coupled with their potent antioxidative property, which can provide additional benefits in the inhibition of oxidative stress and hence in the prevention and treatment of diabetes as well as diabetes linked hyperlipidemia. PMID:26417304

  10. CysLT1R downregulation reverses intracerebroventricular streptozotocin-induced memory impairment via modulation of neuroinflammation in mice.

    PubMed

    Ghosh, Arijit; Chen, Fang; Wu, Feng; Tang, Su-Su; Hu, Mei; Long, Yan; Sun, Hong-Bin; Kong, Ling-Yi; Hong, Hao

    2017-02-06

    Our previous studies showed that cysteinyl leukotrienes receptor 1 (CysLT1R) is upregulated in amyloid-β (Aβ)-induced neurotoxicity and that administration of CysLT1R antagonists such as pranlukast or montelukast can ameliorate memory impairment in mice. In the current study, we sought to explore the role of CysLT1R in intracerebroventricular streptozotocin (STZ-ICV)-induced mouse model of memory impairment and neuroinflammation through shRNA-mediated knockdown of CysLT1R and also its pharmacological blockade by pranlukast. ICR mice were infused with STZ (3.0mg/kg) by a single bilateral stereotaxic ICV microinjection followed by administration of CysLT1R-shRNA (intra-hippocampal) or pranlukast (intragastric, IG). After 21days, a set of behavioral and biochemical tests were performed in order to assess the degree of memory impairment and neuroinflammation in mice. STZ-infused mice spent less time in the target quadrant of Morris water maze test and took more time to find the shock-free arm in modified Y-maze test, which were rescued in the CysLT1R-knockdowned or pranlukast-treated mice. STZ-induced memory impairment was also accompanied by an elevated level of hippocampal CysLT1R, microglial activation, increased IL-1β, and TNF-α. Such elevation of these factors was found to be mediated through the classical NF-κB pathway and administration of CysLT1R-shRNA or pranlukast for 21days reversed all these parameters, suggesting a role of CysLT1R in STZ-induced memory deficit and neuroinflammation.

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

    PubMed

    Anbar, Hanan S; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M

    2016-06-05

    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.

  12. Combination therapy with losartan and L-carnitine protects against endothelial dysfunction of streptozotocin-induced diabetic rats.

    PubMed

    Sleem, Mostafa; Taye, Ashraf; El-Moselhy, Mohamed A; Mangoura, Safwat A

    2014-12-05

    Endothelial dysfunction is a critical factor during the initiation of diabetic cardiovascular complications and angiotensin II appears to play a pivotal role in this setting. The present study aimed to investigate whether the combination therapy with losartan and the nutritional supplement, L-carnitine can provide an additional protection against diabetes-associated endothelial dysfunction and elucidate the possible mechanism(s) underlying this effect. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) in rat. Effects of losartan (20 mg/kg, orally, 3 months) and L-carnitine (200 mg/kg, orally, 3 months) on tumor necrosis factor (TNF)-α, oxidative stress parameters, endothelial nitric oxide synthase expression (eNOS), and vascular function were evaluated. Our results showed a marked increase in aortic superoxide anion (O2(-)) production and serum malondialdehyde (MDA) level alongside attenuating antioxidant enzyme capacities in diabetic rats. This was associated with a significant increase in anigiotensin II type 1 receptor gene expression and TNF-α serum level of diabetic rats alongside reducing aortic eNOS gene expression and nitric oxide (NO) bioavailability. The single or combined administration of losartan and L-carnitine significantly inhibited these changes. Additionally, the vascular endothelium-dependent relaxation with acetylcholine (ACh) in aortic diabetic rat was significantly ameliorated by the single and combined administration of losartan or L-carnitine. Noteworthy, the combination therapy exhibited a more profound response over the monotherapy. Collectively, our results demonstrate that the combined therapy of losartan and L-carnitine affords additive beneficial effects against diabetes-associated endothelial dysfunction, possibly via normalizing the dysregulated eNOS and reducing the inflammation and oxidative stress in diabetic rats.

  13. Antioxidant effects of maslinic acid in livers, hearts and kidneys of streptozotocin-induced diabetic rats: effects on kidney function.

    PubMed

    Mkhwanazi, Blessing N; Serumula, Metse R; Myburg, Rene B; Van Heerden, Fanie R; Musabayane, Cephas T

    2014-04-01

    Studies indicate that hyperglycemia-induced oxidative stress triggers the development of microvascular and macrovascular complications in diabetes. Accordingly, we hypothesized that maslinic acid (MA) prevents these complications due to its antioxidant properties. We, therefore, investigated the effects of 5-week MA treatment of streptozotocin (STZ)-induced diabetic rats on anti-oxidative status of cardiac, hepatic and renal tissues as well as on kidney function. Proximal tubular effects of MA were studied in anesthetized rats challenged with hypotonic saline after a 3.5 h equilibration for 4 h of 1 h control, 1.5 h treatment and 1.5 h recovery periods using lithium clearance. MA was added to the infusate during the treatment period. Oral glucose tolerance responses to MA were monitored in rats given a glucose load after an 18 h fast. Compared with untreated diabetic rats, MA-treated diabetic animals exhibited significantly low malondialdehyde (MDA, a marker of lipid peroxidation) and increased the activity of antioxidant enzymes; superoxide dismutase and glutathione peroxidase in hepatic, cardiac and renal tissues. The expressions of gastrocnemius muscle GLUT4 and kidney GLUT1 and GLUT2 were assessed to elucidate the mechanism of the hypoglycemic effects of MA. MA-treatment diminished the expression of GLUT1 and GLUT2 in diabetic kidney and reduced glycemia values of diabetic rats. MA administration increased urinary Na+ outputs and additionally the FENa indicating that at least part of the overall reduction in Na+ reabsorption occurred in the proximal tubules. These results suggest antioxidant effects of MA can ameliorate oxidative stress and improve kidney function in diabetes mellitus.

  14. Effects of panax quinquefolium on streptozotocin-induced diabetic rats: role of C-peptide, nitric oxide and oxidative stress

    PubMed Central

    Amin, Kamal Adel; Awad, Ezzat Mohamed; Nagy, Mohammed Ahmad

    2011-01-01

    Background: Insulin-dependent diabetes mellitus are at high risk for vascular disorders as hypertension and nephropathy. Ginseng is one of the most widely used herbal medicines and is reported to have a wide range of therapeutic and pharmacological applications for antioxidant and vasorelaxation although the mechanism is not clear. This study, aimed to evaluate hypoglycemic, antioxidant and vasodilator effects of Panax quinquefolium aqueous ginseng extract (AGE) against streptozotocin (STZ)-induced diabetes in male rats. Furthermore explore the role of AGE in C-peptide and nitric oxide (NO) and their relation in STZ induced diabetic rats. Methods: Thirty White male Sprague daw-ley rats weighing 150-200 gm, about 4 month old were equally divided into the following: a control group (normal, nondiabetic), a diabetic group induced by intraperitoneal (I/P) injection of STZ (non-AGE-treated) and an AGE-treated diabetic group (STZ+AGE) (for 8 days). Serum level of urea, creatinine, glucose, insulin, C-peptide and NO were analyzed. Activities of hepatic glucose-6-phosphatase (G6Pase), hepatic glycogen phosphorylase and the renal antioxidant enzyme, catalase were analyzed. Also renal oxidative stress marker malondialdehyde (MDA) was measured. Results: Data showed that STZ treated rats produced a significant increased level of serum urea, creatinine, glucose, NO and renal MDA. Also, induced significantly higher activities of hepatic G6Pase and glycogen phosphorylase compared with controls, while give significant lowered serum insulin, C-peptide level and renal catalase activity. Whereas treatment with AGE led to a significant amelioration in the hyperglycemia (lower the activity of G6Pase and glycogen phosphorylase), hyperinsulinemia and oxidative stress markers. Besides declining the higher level of renal function test and NO. Conclusions: STZ induced-diabetes (DM) associated with renal function disturbances, hypoinsulinemia, defective antioxidant stability and increased

  15. Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes.

    PubMed

    Go, Hyeon-Kyu; Rahman, Md Mahbubur; Kim, Gi-Beum; Na, Chong-Sam; Song, Choon-Ho; Kim, Jin-Shang; Kim, Shang-Jin; Kang, Hyung-Sub

    2015-10-15

    The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of β-cells maintaining normal insulin and glucose

  16. (-)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice.

    PubMed

    Lin, Cheng-Hsiu; Wu, Jin-Bin; Jian, Jia-Ying; Shih, Chun-Ching

    2017-01-01

    synthesis and lipid accumulation within adipose tissue, and consequently, to lower triglyceride levels in liver, blood, and adipose tissue. Moreover, BB treatment not only displayed the activation Akt in liver tissue and skeletal muscle, but also in C2C12 myotube to cause an increase in phosphorylation of Akt in the absence of insulin. These results demonstrated that BB act as an activator of AMPK and /or regulation of insulin pathway (Akt), and the antioxidant activity within the pancreas. Therefore, BB treatment ameliorated the diabetic and dyslipidemic state in STZ-induced diabetic mice.

  17. Effect of Trigonella foenum-graecum (fenugreek) extract on blood glucose, blood lipid and hemorheological properties in streptozotocin-induced diabetic rats.

    PubMed

    Xue, Wan-Li; Li, Xuan-She; Zhang, Jian; Liu, Yong-Hui; Wang, Zhi-Lun; Zhang, Rui-Juan

    2007-01-01

    Trigonella foenum-graecum (fenugreek) seeds have previously been shown to have hypoglycemic and hypocholesterolemic effects on type 1 and type 2 diabetes mellitus patients and experimental diabetic animals. The Trigonella foenum-graecum extract has now been investigated for its effects on general properties, blood glucose and blood lipid, and hemorheological parameters in experimental diabetic rats. Streptozotocin-induced diabetic rats were administrated by oral intragastric intubation separately with low dose (0.44 g/kg.d), middle dose (0.87 g/kg.d), high dose (1.74 g/kg.d) of Trigonella foenum-graecum extract, and Metformin HCl (0.175 g/kg.d) for 6 weeks. Compared with diabetic group, rats treated with Trigonella foenum-graecum extract had an increase in body weight and a decrease in kidney /body weight ratio (p<0.05). Compared with diabetic group, rats treated Trigonella foenum-graecum extract had lower blood glucose, glycated hemoglobin, triglycerides, total cholestrol and higher higher-density-lipoprotein-cholesterol in a dose-dependent manner (p<0.05). The plasma viscosity, whole blood viscosity of high shear rate (200 s-1) and low shear rate (40 s-1), erythrocyte sedimentation rate, whole blood reduction viscosity and platelet conglutination were significantly reduced in diabetic rats treated with high and middle doses of Trigonella foenum-graecum extract, but not in those treated with low dose of Trigonella foenum-graecum extract. It may be concluded that Trigonella foenum-graecum extract can lower kidney /body weight ratio, blood glucose, blood lipid levels and improve hemorheological properties in experimental diabetic rats following repeated treatment for 6 weeks.

  18. The combined effect of metformin and L-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats.

    PubMed

    Salman, Zenat K; Refaat, Rowaida; Selima, Eman; El Sarha, Ashgan; Ismail, Menna A

    2013-08-15

    Increasing evidence has established causative links between obesity, chronic inflammation and insulin resistance; the core pathophysiological feature in type 2 diabetes mellitus. This study was designed to examine whether the combination of L-cysteine and metformin would provide additional benefits in reducing oxidative stress, inflammation and insulin resistance in streptozotocin-induced type 2 diabetes in rats. Male Wistar rats were fed a high-fat diet (HFD) for 8 weeks to induce insulin resistance after which they were rendered diabetic with low-dose streptozotocin. Diabetic rats were treated with metformin (300 mg/kg/day), L-cysteine (300 mg/kg/day) and their combination along with HFD for another 2 weeks. Control rats were fed normal rat chow throughout the experiment. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index (HOMA-IR) and serum free fatty acids (FFAs) were measured. Serum levels of the inflammatory markers; monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and nitrite/nitrate were also determined. The liver was isolated and used for determination of malondialdehyde (MDA), reduced glutathione (GSH), caspase-3 and cytochrome c levels. The hypoglycemic effect of the combination therapy exceeded that of metformin and L-cysteine monotherapies with more improvement in insulin resistance. All treated groups exhibited significant reductions in serum FFAs, oxidative stress and inflammatory parameters, caspase-3 and cytochrome c levels compared to untreated diabetic rats with the highest improvement observed in the combination group. In conclusion, the present results clearly suggest that L-cysteine can be strongly considered as an adjunct to metformin in management of type 2 diabetes.

  19. STREPTOZOTOCIN-INDUCED DIABETES PARTIALLY ATTENUATES THE EFFECTS OF A HIGH-FAT DIET ON LIVER AND BRAIN FATTY ACID COMPOSITION IN MICE

    PubMed Central

    Levant, Beth; Ozias, Marlies K.; Guilford, Brianne L.; Wright, Douglas E.

    2013-01-01

    The current study addresses the effects of a high-fat diet on liver and brain fatty acid compositions and the interaction of that diet with diabetes in a type 1 mouse model. Adult, male, normal and streptozotocin-induced diabetic C57BL/6 mice were fed standard (14% kcals from fat) or high-fat (54% kcals from fat, hydrogenated vegetable shortening and corn oil) diets for 8 weeks. Liver and whole brain total phospholipid fatty acid compositions were then determined by TLC/GC. In the liver of non-diabetic mice, the high-fat diet increased the percentages of 18:1n-9, 20:4n-6, and 22:5n-6 and decreased 18:2n-6 and 22:6n-3. Diabetes increased 16:0 in liver, and decreased 18:1n-7 and 20:4n-6. The effects of the high-fat diet on liver phospholipids in diabetic mice were similar to those in non-diabetic mice, or were of smaller magnitude. In the brain, the high-fat diet increased 18:0 and 20:4n-6 of non-diabetic, but not diabetic mice. Brain 22:5n-6 acid was increased by the high-fat diet in both non-diabetic and diabetic mice, but this increase was smaller in diabetic mice. Diabetes alone did not alter the percentage of any individual fatty acid in brain. This indicates that the effects of a high-fat diet on liver and brain phospholipid fatty acid compositions are mitigated by concomitant hyperglycemia with hypoinsulinemia. PMID:23893338

  20. Paclitaxel therapy potentiates cold hyperalgesia in streptozotocin-induced diabetic rats through enhanced mitochondrial reactive oxygen species production and TRPA1 sensitization.

    PubMed

    Barrière, David André; Rieusset, Jennifer; Chanteranne, Didier; Busserolles, Jérôme; Chauvin, Marie-Agnès; Chapuis, Laëtitia; Salles, Jérôme; Dubray, Claude; Morio, Béatrice

    2012-03-01

    Diabetes comorbidities include disabling peripheral neuropathy (DPN) and an increased risk of developing cancer. Antimitotic drugs, such as paclitaxel, are well known to facilitate the occurrence of peripheral neuropathy. Practitioners frequently observe the development or co-occurrence of enhanced DPN, especially cold sensitivity, in diabetic patients during chemotherapy. Preclinical studies showed that reactive oxygen species (ROS) and cold activate transient receptor potential ankyrin-1 (TRPA1) cation channels, which are involved in cold-evoked pain transduction signaling in DPN. Additionally, paclitaxel treatment has been associated with an accumulation of atypical mitochondria in the sensory nerves of rats. We hypothesized that paclitaxel might potentiate cold hyperalgesia by increasing mitochondrial injuries and TRPA1 activation. Thus, the kinetics of paclitaxel-induced cold hyperalgesia, mitochondrial ROS production, and TRPA1 expression were evaluated in dorsal root ganglia of normoglycemic and streptozotocin-induced diabetic rats. In diabetic rats, paclitaxel significantly enhanced cold hyperalgesia in comparison to normoglycemic paclitaxel-treated control rats. These effects were prevented by N-acetyl-cysteine, a reducing agent, and by HC030031, an antagonist of TRPA1. In diabetic and control rats, paclitaxel treatment was associated with an accumulation of atypical mitochondria and a 2-fold increase in mitochondrial ROS production. Moreover, mRNA levels of glutathione peroxidase 4 and glutathione-S-reductase were significantly lower in diabetic groups treated with paclitaxel. Finally, TRPA1 gene expression was enhanced by 45% in diabetic rats. Paclitaxel potentiation of cold hyperalgesia in diabetes may result from the combination of increased mitochondrial ROS production and poor radical detoxification induced by paclitaxel treatment and diabetes-related overexpression of TRPA1.

  1. The effects of Yucca schidigera and Quillaja saponaria on DNA damage, protein oxidation, lipid peroxidation, and some biochemical parameters in streptozotocin-induced diabetic rats.

    PubMed

    Fidan, A Fatih; Dündar, Yilmaz

    2008-01-01

    The aim of this study was to examine the effects of Yucca schidigera, Quillaja saponaria, and a mixture of both plants on streptozotocin-induced diabetic rats. Animals were allocated into five groups with 10 rats each. The control (C) and diabetic control group (D) were fed with standard rat feed (SRF). The other diabetic groups, the Y. schidigera group (DY), the Q. saponaria group (DQ), and the mix group (DQY), were fed ad libitum using SRF+100 ppm Y. schidigera powder (Sarsaponin 30), SRF+100 ppm Q. saponaria powder (Nutrafito), and SRF+100 ppm Y. schidigera-Q. saponaria powder (Nutrafito Plus), respectively, for 3 weeks. The blood glucose level was found to be significantly lower in the DY and DQ groups than in the D and DQY groups (P<.001). The insulin levels increased in the DY and DQY groups (P<.05). Plasma cholesterol and triglyceride levels in the DY, DQ, and DQY groups significantly decreased compared to those of the D group (P<.01, P<.001, respectively). HDL in the diabetic groups significantly increased in the DQ and DQY groups (P<.05), while LDL did not show any significant change. Mononuclear leukocyte DNA damage, plasma malondialdehyde, and plasma protein carbonyl levels were found to be significantly lower (P<.001, P<.001, P<.05, respectively) in the DY, DQ, and DQY groups according to the D group. The low level of nitric oxide in diabetic rats increased in the DQ group (P<.01). Total antioxidant capacity between groups did not differ. Our results thus suggested that Q. saponaria and Y. schidigera powders could help in the treatment of the disease owing to their hypoglycemic, hypocholesterolemic, and antioxidant effects.

  2. Insulinotropic and β-cell protective action of cuminaldehyde, cuminol and an inhibitor isolated from Cuminum cyminum in streptozotocin-induced diabetic rats.

    PubMed

    Patil, Swapnil B; Takalikar, Shreehari S; Joglekar, Madhav M; Haldavnekar, Vivek S; Arvindekar, Akalpita U

    2013-10-01

    Cuminum cyminum, a commonly used spice, is known to have anti-diabetic action. The present study aims towards the isolation of bioactive components from C. cyminum and the evaluation of their insulin secretagogue potential with the probable mechanism and β-cell protective action. The anti-diabetic activity was detected in the petroleum ether (pet ether) fraction of the C. cyminum distillate and studied through in vivo and in vitro experiments. Bioactive components were identified through GC-MS, Fourier transform infrared spectroscopy and NMR analysis. The isolated components were evaluated for their insulin secretagogue action using rat pancreatic islets. Further, the probable mechanism of stimulation of islets was evaluated through in vitro studies using diazoxide, nifedipine and 3-isobutyl-1-methylxanthine. β-Cell protection was evaluated using the (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan) (MTT) assay, the alkaline comet assay and nitrite production. The administration of the pet ether fraction for 45 d to streptozotocin-induced diabetic rats revealed an improved lipid profile. Cuminaldehyde and cuminol were identified as potent insulinotrophic components. Cuminaldehyde and cuminol (25 μg/ml) showed 3·34- and 3·85-fold increased insulin secretion, respectively, than the 11·8 mm-glucose control. The insulinotrophic action of both components was glucose-dependent and due to the closure of the ATP-sensitive K (K⁺-ATP) channel and the increase in intracellular Ca²⁺ concentration. An inhibitor of insulin secretion with potent β-cell protective action was also isolated from the same pet ether fraction. In conclusion, C. cyminum was able to lower blood glucose without causing hypoglycaemia or β-cell burn out. Hence, the commonly used spice, C. cyminum, has the potential to be used as a novel insulinotrophic therapy for prolonged treatment of diabetes.

  3. Pancreatic islet regeneration and some liver biochemical parameters of leaf extracts of Vitex doniana in normal and streptozotocin-induced diabetic albino rats

    PubMed Central

    Oche, Okpe; Sani, Ibrahim; Chilaka, Njoku Godwin; Samuel, Ndidi Uche; Samuel, Atabo

    2014-01-01

    Objective To test two water soluble extracts (aqueous and ethanolic) obtained from the leaves of Vitex doniana in normal and streptozotocin-induced diabetic rats for their effects on pancreatic endocrine tissues and serum marker enzymes for a period of 21 d. Methods A total of 55 rats divided into 11 groups of 5 rats each were assigned into diabetic and non-diabetic groups and followed by a daily administration of ethanolic and aqueous extracts for 21 d. Group 1 was the normal control while group 7 was treated with standard drug. Results The histopathological studies of the diabetic rats indicated increase in the volume density of islets, percent of β-cells and size of islet in the groups that received the plant extracts, which suggested regeneration of β-cells along with β-cells repairs, as compared with the non-treated diabetic control which showed complete degeneration of the islet cells. There was significant reduction (P<0.05) in the serum activities of marker enzymes, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in diabetes treated rats, whereas an insignificant increase (P>0.01) in the serum activities of marker enzymes was observed for non-diabetic treated rats. Results of total bilirubin, direct bilirubin and unconjugated bilirubin showed that diabetic control group was significantly higher (P<0.05) in total bilirubin and unconjugated bilirubin compared with treated groups while non-diabetic treated groups showed no significant increase (P>0.01) in total bilirubin and direct bilirubin compared with the normal control. Conclusion This herbal therapy appears to bring about repair/regeneration of the endocrine pancreas and hepatic cells protection in the diabetic rat. PMID:25182283

  4. Effects of N-Acetylcysteine on Nicotinamide Dinucleotide Phosphate Oxidase Activation and Antioxidant Status in Heart, Lung, Liver and Kidney in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Lei, Shaoqing; Liu, Yanan; Liu, Huimin; Yu, Hong; Wang, Hui

    2012-01-01

    Purpose Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress plays a key role in the pathogenesis of diabetic complications. Nicotinamide dinucleotide phosphate (NADPH) oxidase is one of the major sources of ROS production in diabetes. We, therefore, examined the possibility that NADPH oxidase activation is increased in various tissues, and that the antioxidant N-acetylcysteine (NAC) may have tissue specific effects on NADPH oxidase and tissue antioxidant status in diabetes. Materials and Methods Control (C) and streptozotocin-induced diabetic (D) rats were treated either with NAC (1.5 g/kg/day) orally or placebo for 4 weeks. The plasma, heart, lung, liver, kidney were harvested immediately and stored for biochemical or immunoblot analysis. Results levels of free 15-F2t-isoprostane were increased in plasma, heart, lung, liver and kidney tissues in diabetic rats, accompanied with significantly increased membrane translocation of the NADPH oxidase subunit p67phox in all tissues and increased expression of the membrane-bound subunit p22phox in heart, lung and kidney. The tissue antioxidant activity in lung, liver and kidney was decreased in diabetic rats, while it was increased in heart tissue. NAC reduced the expression of p22phox and p67phox, suppressed p67phox membrane translocation, and reduced free 15-F2t-isoprostane levels in all tissues. NAC increased antioxidant activity in liver and lung, but did not significantly affect antioxidant activity in heart and kidney. Conclusion The current study shows that NAC inhibits NADPH oxidase activation in diabetes and attenuates tissue oxidative damage in all organs, even though its effects on antioxidant activity are tissue specific. PMID:22318816

  5. Absorption, transport and insulin-mimetic properties of bis(maltolato)oxovanadium (IV) in streptozotocin-induced hyperglycemic rats by integrated mass spectrometric techniques.

    PubMed

    Iglesias-González, T; Sánchez-González, C; Montes-Bayón, M; Llopis-González, J; Sanz-Medel, A

    2012-01-01

    The use of V(IV) complexes as insulin-enhancing agents has been increasing during the last decade. Among them, 3-hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven to be especially suitable as ligands for vanadyl ions. In fact, they have passed phase I and phase II clinical trials, respectively. However, the mechanism through which those drugs exert their insulin-mimetic properties is still not fully understood. Thus, the aim of this study is to obtain an integrated picture of the absorption, biodistribution and insulin-mimetic properties of the bis(maltolato)oxovanadium (IV) (BMOV) in streptozotocin-induced hyperglycaemic rats. For this purpose, BMOV hypoglycaemic properties were evaluated by monitoring both the circulating glucose and the glycohemoglobin, biomarkers of diabetes mellitus. In both cases, the results were drug concentration dependent. Using doses of vanadium at 3 mg/day, it was possible to reduce the glycaemia of the diabetic rats to almost control levels. BMOV absorption experiments have been conducted by intestinal perfusion revealing that approximately 35% of V is absorbed by the intestinal cells. Additionally, the transport of the absorbed vanadium (IV) by serum proteins was studied. For this purpose, a speciation strategy using high-performance liquid chromatography (HPLC) for separation and inductively coupled serum mass spectrometry, ICP-MS, for detection has been employed. The obtained HPLC-ICP-MS results, confirmed by MALDI-MS data, showed evidence that V, administered orally, is uniquely bound to transferrin in rat serum.

  6. Ellagic acid inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and prevents atheroma formation in streptozotocin-induced diabetic rats.

    PubMed

    Rani, Uma P; Kesavan, Rushendhiran; Ganugula, Raghu; Avaneesh, T; Kumar, Uday P; Reddy, G Bhanuprakash; Dixit, Madhulika

    2013-11-01

    Plant-derived polyphenolic compounds have beneficial health effects. In the present study, we determined the ability of ellagic acid (EA) to prevent platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of primary cultures of rat aortic smooth muscle cells (RASMCs). We also determined the ability of EA to prevent atherosclerosis in streptozotocin-induced diabetic rats. Proliferation of cells was measured via Alamar Blue assay and through propidium iodide-based cell cycle analysis in flow cytometer. Reactive oxygen species (ROS) were measured via 2',7'-dichlorofluorescin diacetate and Amplex red methods. Expression of proliferation markers and activation of kinases were assessed by immunoblot analysis. Cotreatment of primary cultures of RASMCs with 25 μmol/L of EA significantly reduced PDGF-BB (20 ng/ml)-induced proliferation by blocking S-phase entry. EA effectively blocked PDGF receptor-β (PDGFR-β) tyrosine phosphorylation, generation of intracellular ROS and downstream activation of extracellular signal-regulated kinase 1/2. It also blocked PDGF-BB-induced expression of cyclin D1. Computational molecular docking of EA with the PDGFR-β-PDGF-BB complex revealed two putative inhibitor binding sites which showed similar binding energies with the known PDGFR-β inhibitor AG1295. In diabetic rats, supplementation of diet with 2% EA significantly blocked diabetes-induced medial thickness, and lipid and collagen deposition in the arch of aorta. These were assessed through haematoxylin and eosin, Oil Red O and Masson's trichome staining, respectively. EA treatment also blocked cyclin D1 expression in medial smooth muscle cells in experimental animals. Thus, EA is effective in reducing atherosclerotic process by blocking proliferation of vascular smooth muscle cells.

  7. A mixture of extracts from Peruvian plants (black maca and yacon) improves sperm count and reduced glycemia in mice with streptozotocin-induced diabetes.

    PubMed

    Gonzales, Gustavo F; Gonzales-Castañeda, Cynthia; Gasco, Manuel

    2013-09-01

    We investigated the effect of two extracts from Peruvian plants given alone or in a mixture on sperm count and glycemia in streptozotocin-diabetic mice. Normal or diabetic mice were divided in groups receiving vehicle, black maca (Lepidium meyenii), yacon (Smallanthus sonchifolius) or three mixtures of extracts black maca/yacon (90/10, 50/50 and 10/90%). Normal or diabetic mice were treated for 7 d with each extract, mixture or vehicle. Glycemia, daily sperm production (DSP), epididymal and vas deferens sperm counts in mice and polyphenol content, and antioxidant activity in each extract were assessed. Black maca (BM), yacon and the mixture of extracts reduced glucose levels in diabetic mice. Non-diabetic mice treated with BM and yacon showed higher DSP than those treated with vehicle (p < 0.05). Diabetic mice treated with BM, yacon and the mixture maca/yacon increased DSP, and sperm count in vas deferens and epididymis with respect to non-diabetic and diabetic mice treated with vehicle (p < 0.05). Yacon has 3.05 times higher polyphenol content than in maca, and this was associated with higher antioxidant activity. The combination of two extracts improved glycemic levels and male reproductive function in diabetic mice. Streptozotocin increased 1.43 times the liver weight that was reversed with the assessed plants extracts. In summary, streptozotocin-induced diabetes resulted in reduction in sperm counts and liver damage. These effects could be reduced with BM, yacon and the BM+yacon mixture.

  8. Cell-specific expression of X-linked inhibitor of apoptosis in the anterior pituitary of streptozotocin-induced diabetic rats.

    PubMed

    Arroba, Ana I; Lechuga-Sancho, Alfonso M; Frago, Laura M; Argente, Jesús; Chowen, Julie A

    2007-01-01

    Cell death is increased in the anterior pituitary of poorly controlled diabetic rats, but anti-apoptotic mechanisms are also activated. We hypothesized that specific cell types are selectively protected against diabetes-induced cell death. To determine when anti-apoptotic mechanisms are activated, streptozotocin-induced diabetic rats were killed after 1, 4, 6 and 8 weeks of evolution. Anterior pituitaries were processed for western blot analysis to determine changes in the intrinsic cell death pathway and upstream kinases involved in cell protection mechanisms. An increase in cell death was detected by ELISA at 4 weeks of diabetes. TUNEL labelling demonstrated that this corresponded to death of primarily lactotrophs, a few somatotrophs, and no thyrotrophs, corticotrophs or gonadotrophs. Levels of phosphorylated (p) Akt were increased at 1 week of diabetes, while pERK1/2 levels increased at 4 weeks and pJNK at 6 weeks. Activation of caspase 3 decreased and anti-apoptotic members of the Bcl-2 protein family increased as early as 1 week after diabetes onset. These changes were coincident with increased IGF-I receptor levels. Levels of X-linked inhibitor of apoptosis protein (XIAP) increased significantly after 6 weeks of diabetes, as did activation of nuclear factor (NF)kappaB. Double immunohistochemistry indicated that XIAP was expressed in less than 1% of lactotrophs and gonadotrophs, approximately 50% of somatotrophs and more than 90% of corticotrophs and thyrotrophs. These results suggest that some cell survival mechanisms are rapidly activated in the anterior pituitary, even before increased cell death can be detected, while others are more delayed. Furthermore, both pituitary cell death and expression of protective mechanisms such as XIAP are cell-type specific.

  9. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose.

    PubMed

    Abraham, Pretty Mary; Kuruvilla, Korah P; Mathew, Jobin; Malat, Anitha; Joy, Shilpa; Paulose, C S

    2010-09-25

    Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT(2A) receptor subtype, gene expression studies on 5-HT(2A), 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters B(max) and Kd showed a significant decrease (p < 0.001) whereas 5-HT(2A) receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT(2A), 5-HTT and INSR in hippocampus showed a significant down regulation (p < 0.001) in diabetic rats compared to control. Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, B(max), Kd of 5-HT, 5-HT(2A) and gene expression of 5-HT(2A), 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT(2A) and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p < 0.001) anxiety-related traits in diabetic rats which were corrected by combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.

  10. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose

    PubMed Central

    2010-01-01

    Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT2A receptor subtype, gene expression studies on 5-HT2A, 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters Bmax and Kd showed a significant decrease (p < 0.001) whereas 5-HT2A receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p < 0.001) in diabetic rats compared to control. Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, Bmax , Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p < 0.001) anxiety-related traits in diabetic rats which were corrected by combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes. PMID:20868513

  11. Correction of enhanced Na(+)-H+ exchange of rat small intestinal brush-border membranes in streptozotocin-induced diabetes by insulin or 1,25-dihydroxycholecalciferol

    SciTech Connect

    Dudeja, P.K.; Wali, R.K.; Klitzke, A.; Sitrin, M.D.; Brasitus, T.A. )

    1991-05-01

    Diabetes was induced in rats by administration of a single i.p. injection of streptozotocin (50 mg/kg body wt). After 7 d, diabetic rats were further treated with insulin or 1,25-dihydroxycholecalciferol (1,25(OH)2D3) for an additional 5-7 d. Control, diabetic, diabetic + insulin, and diabetic + 1,25(OH)2D3 rats were then killed, their proximal small intestines were removed, and villus-tip epithelial cells were isolated and used to prepare brush-border membrane vesicles. Preparations from each of these groups were then analyzed and compared with respect to their amiloride-sensitive, electroneutral Na(+)-H+ exchange activity, using {sup 22}Na uptake as well as acridine orange techniques. The results of these experiments demonstrated that (a) H+ gradient-dependent {sup 22}Na uptake as well as Na+ gradient-dependent transmembrane H+ fluxes were significantly increased in diabetic vesicles compared to their control counterparts, (b) kinetic studies demonstrated that this enhanced {sup 22}Na uptake in diabetes was a result of increased maximal velocity (Vmax) of this exchanger with no change in apparent affinity (Km) for Na+, (c) serum levels of 1,25(OH)2D3 were significantly lower in diabetic animals compared with their control counterparts; and (d) insulin or 1,25(OH)2D3 treatment restored the Vmax alterations to control values, without any significant changes in Km, concomitant with significantly increasing the serum levels of 1,25(OH)2D3 in diabetic animals. These results indicate that Na(+)-H+ activity is significantly increased in proximal small intestinal luminal membranes of streptozotocin-induced diabetic rats. Moreover, alterations in the serum levels of 1,25(OH)2D3 may, at least in part, explain this enhanced antiporter activity and its correction by insulin.

  12. Antioxidant and anti-inflammatory effects of a hypoglycemic fraction from Cucurbita ficifolia Bouché in streptozotocin-induced diabetes mice.

    PubMed

    Roman-Ramos, R; Almanza-Perez, J C; Fortis-Barrera, A; Angeles-Mejia, S; Banderas-Dorantes, T R; Zamilpa-Alvarez, A; Diaz-Flores, M; Jasso, I; Blancas-Flores, G; Gomez, J; Alarcon-Aguilar, F J

    2012-01-01

    Type 2 diabetes is characterized by oxidative stress and a chronic low-grade inflammatory state, which also play roles in the pathogenesis of this disease and the accompanying vascular complications by increasing the production of free radicals and pro-inflammatory cytokines. Cucurbita ficifolia Bouché (C. ficifolia) is an edible Mexican plant whose hypoglycemic activity has been demonstrated in several experimental and clinical conditions. Recently, D-chiro-inositol has been proposed as the compound responsible for the hypoglycemic effects; however, the antioxidant and anti-inflammatory potential of this plant has not yet been explored. The aim of this research is to study the influence of a hypoglycemic, D-chiro-inositol-containing fraction from the C. ficifolia fruit (AP-Fraction) on biomarkers of oxidative stress, as well as on the inflammatory cytokines in streptozotocin-induced diabetes. The AP-Fraction obtained from the mature fruit of C. ficifolia contained 3.31 mg of D-chiro-inositol/g of AP-Fraction. The AP-Fraction was administrated daily by gavage to normal mice for 15 days as a preventive treatment. Then these animals were given streptozotocin, and the treatments were continued for an additional 33 days. Pioglitazone was used as a hypoglycemic drug for comparison. Administration of the AP-Fraction significantly increased glutathione (GSH) and decreased malondialdehyde (MDA) in the liver without significantly affecting the levels in other tissues. The AP-Fraction reduced TNF-α and increased IL-6 and IFN-γ in serum. Interestingly, the AP-Fraction also increased IL-10, an anti-inflammatory cytokine. These results suggest that C. ficifolia might be used as an alternative medication for the control of diabetes mellitus and that it has antioxidant and anti-inflammatory properties in addition to its hypoglycemic activity.

  13. Effects of Hydro-Alcoholic Extract of Rhus coriaria (Sumac) Seeds on Reproductive Complications of Nicotinamide-Streptozotocin Induced Type-2 Diabetes in Male Mice

    PubMed Central

    Ahangarpour, Akram; Heidari, Hamid; Ehsan, Ghaedi; Rashidi Nooshabadi, Mohammad Reza

    2014-01-01

    Purpose The purpose of this study was to investigate the effects of the hydro-alcoholic extract of Rhus coriaria seeds on the reproductive system of nicotinamide-streptozotocin-induced type-2 diabetic mice. Materials and Methods In this experimental study, 56 male Naval Medical Research Institute mice were randomly divided into seven groups (n=8): control; diabetic mice; diabetic mice administered glibenclamide (0.25 mg/kg); diabetic mice who received the hydro-alcoholic extract of R. coriaria seeds (200 and 400 mg/kg groups); and normal mice who received this extract (200 and 400 mg/kg groups). Diabetes was induced by intraperitoneal administration of streptozotocin (65 mg/kg) 15 minutes after an injection of nicotinamide (120 mg/kg). Then, glibenclamide and the above mentioned extract were administered orally for 28 consecutive days. Twenty-four hours after the last treatment, serum samples, the testes, and the cauda epididymis were removed immediately for hormonal, testis morphology, and sperm parameter assessments. Results Body and testicular weight, sperm count and viability, and serum luteinizing hormone, follicle-stimulating hormone and testosterone levels were significantly lower in the diabetic mice (p<0.05). The diabetic mice treated with 400 mg/kg of the hydro-alcoholic extract of R. coriaria seeds recovered from these reductions (p<0.05). Further, glibenclamide alleviated hormonal and sperm count depletion in diabetes-induced mice (p<0.05). Conclusions The present results indicated that the hydro-alcoholic extract of R. coriaria seeds has anti-infertility effects in diabetic males. PMID:25606564

  14. Coculture with primary visceral rat adipocytes from control but not streptozotocin-induced diabetic animals increases glucose uptake in rat skeletal muscle cells: role of adiponectin.

    PubMed

    Vu, Vivian; Kim, Wi; Fang, Xiangping; Liu, Yuan-Tao; Xu, Aimin; Sweeney, Gary

    2007-09-01

    We developed a coculture system comprising primary rat adipocytes and L6 rat skeletal muscle cells to allow investigation of the effects of physiologically relevant mixtures of adipokines. We observed that coculture, or adipocyte-conditioned media, increased glucose uptake in muscle cells. An adipokine that could potentially mediate this effect is adiponectin, and we demonstrated that small interfering RNA-mediated knockdown of adiponectin receptor-2 in muscle cells reduced the uptake of glucose upon coculture with primary rat adipocytes. Analysis of coculture media by ELISA indicated total adiponectin concentration of up to 1 microg/ml, and Western blotting and gel filtration analysis demonstrated that the adipokine profile was hexamer greater than high molecular weight much greater than trimer. We used the streptozotocin-induced rat model of diabetes and found that high-molecular-weight adiponectin levels decreased in comparison with control animals and this correlated with the fact that diabetic rat-derived primary adipocytes in coculture did not stimulate glucose uptake to the same extent as control adipocytes. Coculture induced phosphorylation of AMP-activated protein kinase (T172) and interestingly also insulin receptor substrate-1 (Y612) and Akt (T308 & S473), which could be attenuated after adiponectin receptor-2-small interfering RNA treatment. In summary, we believe that this coculture system represents an excellent model to study the effects of primary adipocyte-derived adipokine mixtures on skeletal muscle metabolism, and here we have established that in the context of physiologically relevant mixtures of adipokines, adiponectin may be an important determinant of positive cross talk between adipocytes and skeletal muscle.

  15. Effective wound healing in streptozotocin-induced diabetic rats by adipose-derived stromal cell transplantation in plasma-gel containing fragmin/protamine microparticles.

    PubMed

    Sumi, Yuki; Ishihara, Masayuki; Kishimoto, Satoko; Takikawa, Makoto; Hattori, Hidemi; Takikawa, Megumi; Azuma, Ryuichi; Nakamura, Shingo; Fujita, Masanori; Kiyosawa, Tomoharu

    2014-01-01

    We investigated the effectiveness of the application of inbred adipose-derived stromal cells (IR-ASCs) in high inbred rat plasma (IRP) (6%)-Dulbecco modified Eagle medium (DMEM) gel with fragmin/protamine microparticles (F/P MPs) (IR-ASCs + IRP-DMEM gel + F/P MPs) on wound healing in streptozotocin-induced diabetic rats. F/P MPs have previously been used as a cell carrier for IR-ASCs in inbred Fisher 344 rats and for preservation and controlled release of various cytokines in IRP-DMEM gel. We applied IR-ASCs + IRP-DMEM gel + F/P MPs to full-thickness skin excisions on the backs of the diabetic rats. The statistical significance of wound closure was evaluated on postwounding days 3, 7, 10, and 14, and the skin area surrounding the wound was removed for histological examination on days 7 and 14. The wound closure rate and histological examination of wounds treated with IR-ASCs + IRP-DMEM gel + F/P MPs demonstrated significantly advanced epithelialization, capillary formation, and granulation tissue formation. When DiI-labeled IR-ASCs + IRP-DMEM gel + F/P MPs were applied to full-thickness skin wounds on the backs of the diabetic rats, histological observation at 2 weeks showed appearances of both DiI-labeled granulation tissue and CD31-immunostained microvessels in the transplant areas. A portion of the transplanted IR-ASCs + IRP-DMEM gel + F/P MPs had been taken up into the granulation tissues to promote wound healing. Thus, IR-ASCs + IRP-DMEM gel + F/P MPs were effective for repairing healing-impaired wounds such as those arising in the diabetic rats.

  16. Antioxidant effects of isorhamnetin 3,7-di-O-beta-D-glucopyranoside isolated from mustard leaf (Brassica juncea) in rats with streptozotocin-induced diabetes.

    PubMed

    Yokozawa, Takako; Kim, Hyun Young; Cho, Eun Ju; Choi, Jae Sue; Chung, Hae Young

    2002-09-11

    To investigate the effects of isorhamnetin 3,7-di-O-beta-D-glucopyranoside (isorhamnetin diglucoside), a major flavonoid compound of mustard leaf, on oxidative stress due to diabetes mellitus, in vivo and in vitro studies were carried out. Oral administration of isorhamnetin diglucoside (10 or 20 mg/kg of body weight/day for 10 days) to rats with streptozotocin-induced diabetes significantly reduced serum levels of glucose and 5-(hydroxymethyl)furfural (5-HMF), which is glycosylated with hemoglobin and is an indicator of oxidative stress. After intraperitoneal administration, isorhamnetin diglucoside did not show these activities. In addition, after oral administration, the thiobarbituric acid-reactive substance levels of serum, and liver and kidney mitochondria declined significantly compared with the control group in a dose-dependent manner, whereas after intraperitoneal administration these levels fell only slightly. On the basis of the oral and intraperitoneal results, it was hypothesized that isorhamnetin diglucoside was converted to its metabolite in vivo, and its conversion to its aglycone, isorhamnetin, by beta-glucosidase was confirmed; isorhamnetin acted as an antioxidant. Moreover, it was observed that isorhamnetin diglucoside had no effect on the 1,1-diphenyl-2-picrylhydrazyl radical, whereas isorhamnetin showed a potent antioxidant effect in vitro. In addition, intraperitoneal administration of isorhamnetin reduced serum glucose and 5-HMF levels. Furthermore, lipid peroxidation in blood, liver, and kidney associated with diabetes mellitus declined after the administration of isorhamnetin. These results suggest that isorhamnetin diglucoside is metabolized in vivo by intestinal bacteria to isorhamnetin and that isorhamnetin plays an important role as an antioxidant.

  17. Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrosomic offspring of rats with streptozotocin-induced diabetes.

    PubMed

    Merzouk, H; Madani, S; Chabane Sari, D; Prost, J; Bouchenak, M; Belleville, J

    2000-01-01

    The aim of this investigation was to determine the time course of changes in serum glucose, insulin and lipid levels, as well as lipid and protein content and lipolytic activities in insulin target organs (liver, adipose tissue and muscle), in macrosomic offspring of streptozotocin-induced mildly hyperglycaemic rats. Food intake and nutritional efficiency were also evaluated. Mild hyperglycaemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups (birth weight >1.7 S.D. greater than the mean value for the control pups) had higher serum insulin, glucose and lipid levels than control pups. These macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight up to 12 weeks of age. These rats were not hyperphagic; however, they had higher food efficiency and fat storage capacity with higher adipocyte lipoprotein lipase activity, which contributed to persisting obesity. Hepatic lipase activity was increased in macrosomic rats at all ages. Moreover, macrosomia was associated with metabolic disturbances that varied according to age and sex. After 1 month, several alterations observed at birth had disappeared. Serum glucose, insulin and lipid levels in male and female macrosomic rats became similar to those of their respective controls. At 2 months of age, hepatic and serum triacylglycerol levels were higher in macrosomic females than in controls. By 3 months, macrosomic rats (both males and females) had developed insulin resistance with hyperinsulinaemia, hyperglycaemia, and higher serum and hepatic lipids. In conclusion, macrosomia was associated with alterations in glucose and lipid metabolism through to adulthood. It should be considered as an important potential risk factor for obesity and its metabolic complications.

  18. Diabetic therapeutic effects of ethyl acetate fraction from the roots of Musa paradisiaca and seeds of Eugenia jambolana in streptozotocin-induced male diabetic rats.

    PubMed

    Panda, D K; Ghosh, Debidas; Bhat, B; Talwar, S K; Jaggi, M; Mukherjee, R

    2009-11-01

    The folklore medicine of primitive people has been greatly appreciated for centuries. Many researchers study the curative efficiency and mode of action of various medicinal plants. Serum glucose level, lipid profile, glucose tolerance, hepatic and muscle glycogen contents as well as the activities of hepatic hexokinase and glucose-6-phosphatase recovered significantly after oral administration of ethyl acetate fractions of Eugenia jambolana (E. jambolana) or Musa paradisiaca (M. paradisiaca) in separate (E. jambolana L.: 200 mg/kg of body weight and M. paradisiaca: 100 mg/kg of body weight) or combined form for 90 days (twice a day through gavage) to streptozotocin-induced diabetic rats. The loss in body weight of diabetic animals was reversed and serum levels of insulin as well as C-peptide, which were found to be reduced in diabetic rats, increased significantly after oral administration of the fractions. A histological study of the rats' pancreas revealed that after 90 days of oral treatment with the plant fractions in separate or combined form, the size and volume of pancreatic islets in diabetic treated rats increased significantly compared with the diabetic control group. Treatment of diabetic rats with the combined dose (300 mg/kg of body weight) of plant fractions (200 mg E. jambolana and 100 mg M. paradisiaca) was found to be more effective than treatment with the individual fraction. The doses of E. jambolana and M. paradisiaca selected for this study are the optimum antihyperglycemic doses of the plant fractions, which were determined after conducting a dose-dependent study at various dose levels (50-500 mg/kg) in our pilot experiments. The plant fractions were found to be free from metabolic toxicity. Through HPTLC finger printing, three different compounds were noted in the ethyl acetate fraction of E. jambolana L. and eight different compounds in the ethyl acetate fraction of M. paradisiaca L.

  19. Concentration of Zinc, Copper, Iron, Calcium, and Magnesium in the Serum, Tissues, and Urine of Streptozotocin-Induced Mild Diabetic Rat Model.

    PubMed

    Gómez, Tahiry; Bequer, Leticia; Mollineda, Angel; Molina, José L; Álvarez, Alain; Lavastida, Mayrelis; Clapés, Sonia

    2017-03-03

    The present study aimed to investigate, in the streptozotocin-induced mild diabetic rat model, the zinc (Zn), copper (Cu), iron (Fe), calcium (Ca), and magnesium (Mg) concentration in serum, liver, and kidney tissues, and urine samples from adult Wistar rats treated neonatally with streptozotocin (STZ). Diabetes was induced by subcutaneous administration of streptozotocin (100 mg/Kg) in female Wistar rats of 2 days old (STZ, n = 10). Control group (CG, n = 10) received only sodium-citrate buffer. The mineral concentrations were measured by atomic absorption spectrophotometry. The validity and accuracy were checked by conventional methods. STZ neonatal injection successfully leaded to mild diabetes in the adult rats. Serum concentrations of Zn, Cu, Fe, Ca, and Mg showed no changes (p > 0.05) due to diabetes. The Zn, Fe, Ca, and Mg concentrations in liver and kidney tissues were not different (p > 0.05) between STZ and CG. The mean values of Cu were higher (p < 0.05) in liver and kidney samples from STZ as compared to CG. Urine minerals concentrations (Zn, Cu, Fe and Ca) in STZ-rats group were lower (p < 0.05) than CG. However, the content of all evaluated minerals in the excreted urine were higher (p < 0.01) in STZ-rats during a 24 h collection period. Urinary excretion of Zn, Cu, Fe, Ca, and Mg was strongly correlated with urinary volume during the 24 h period (r > 0.7; p < 0.001). Observed changes in mineral metabolism of STZ-induced mild diabetes model could be due to the endocrine imbalance associated with the diabetic condition.

  20. Cholecystokinin expression in the β-cell leads to increased β-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis.

    PubMed

    Lavine, Jeremy A; Kibbe, Carly R; Baan, Mieke; Sirinvaravong, Sirinart; Umhoefer, Heidi M; Engler, Kimberly A; Meske, Louise M; Sacotte, Kaitlyn A; Erhardt, Daniel P; Davis, Dawn Belt

    2015-11-15

    Cholecystokinin (CCK) is a peptide hormone produced in the gut and brain with beneficial effects on digestion, satiety, and insulin secretion. CCK is also expressed in pancreatic β-cells, but only in models of obesity and insulin resistance. Whole body deletion of CCK in obese mice leads to reduced β-cell mass expansion and increased apoptosis. We hypothesized that islet-derived CCK is important in protection from β-cell apoptosis. To determine the specific role of β-cell-derived CCK in β-cell mass dynamics, we generated a transgenic mouse that expresses CCK in the β-cell in the lean state (MIP-CCK). Although this transgene contains the human growth hormone minigene, we saw no expression of human growth hormone protein in transgenic islets. We examined the ability of MIP-CCK mice to maintain β-cell mass when subjected to apoptotic stress, with advanced age, and after streptozotocin treatment. Aged MIP-CCK mice have increased β-cell area. MIP-CCK mice are resistant to streptozotocin-induced diabetes and exhibit reduced β-cell apoptosis. Directed CCK overexpression in cultured β-cells also protects from cytokine-induced apoptosis. We have identified an important new paracrine/autocrine effect of CCK in protection of β-cells from apoptotic stress. Understanding the role of β-cell CCK adds to the emerging knowledge of classic gut peptides in intraislet signaling. CCK receptor agonists are being investigated as therapeutics for obesity and diabetes. While these agonists clearly have beneficial effects on body weight and insulin sensitivity in peripheral tissues, they may also directly protect β-cells from apoptosis.

  1. Cardioprotection from emulsified isoflurane postconditioning is lost in rats with streptozotocin-induced diabetes due to the impairment of Brg1/Nrf2/STAT3 signalling.

    PubMed

    Wang, Yan; Li, Haobo; Huang, Huansen; Liu, Shiming; Mao, Xiaowen; Wang, Sheng; Wong, Stanley Sau-Ching; Xia, Zhengyuan; Irwin, Michael G

    2016-05-01

    Isoflurane postconditioning (IsoPostC) attenuates myocardial ischaemia/reperfusion injury (IRI). Signal transducer and activator of transcription-3 (STAT3) is critical in ischaemic postconditioning cardioprotection, which can be regulated by the Brahma-related gene (Brg1) and nuclear factor-erythroid 2-related factor 2 (Nrf2), although they are both reduced in diabetic hearts. We hypothesized that reduced Brg1/Nrf2 and STAT3 activation may jeopardize IsoPostC-mediated cardioprotection in diabetic hearts. In the present study, Langendorff-perfused, non-diabetic (control) and 8-week-old streptozotocin-induced Type 1 diabetic rat hearts were subjected to 30 min of global ischaemia and 120 min of reperfusion without or with IsoPostC, which was achieved by administering emulsified isoflurane (2.0%, v/v) in Krebs-Henseleit (KH) solution immediately at the onset of reperfusion for 10 min and switching to KH solution perfusion alone thereafter. Cultured H9C2 cells were exposed to normal glucose (NG, 5.5 mM) or high glucose (HG, 30 mM) and subjected to hypoxia/reoxygenation (HR) in the presence or absence of IsoPostC. Diabetic rats displayed larger post-ischaemic myocardial infarction and more severe haemodynamic dysfunction, associated with increased myocardial oxidative stress and reduced cardiac Brg1, Nrf2 and STAT3 phosphorylation/activation (p-STAT3), compared with controls. These changes were reversed/prevented by IsoPostC in control but not in diabetic rats. In H9C2 cells exposed to NG but not HG, IsoPostC significantly attenuated HR-induced cellular injury and superoxide anion production with increased Brg1, Nrf2 and p-STAT3. These beneficial effects of IsoPostC were abolished by Brg1, Nrf2 or STAT3 gene knockdown. Brg1 or Nrf2 gene knockdown abolished IsoPostC-induced STAT3 activation. N-acetylcysteine restored Brg1, Nrf2 and p-STAT3, and IsoPostC-induced protection in H9C2 cells exposed to HG and HR. In conclusion, IsoPostC confers cardioprotection through

  2. Moderate exercise combined with dietary vitamins C and E counteracts oxidative stress in the kidney and lens of streptozotocin-induced diabetic-rat.

    PubMed

    Kutlu, Mehmet; Naziroğlu, Mustafa; Simşek, Halil; Yilmaz, Turgut; Sahap Kükner, A

    2005-01-01

    Oxidative stress has a key role in the pathogenesis of diabetes-induced cataract formation and nephropathy. Daily moderate exercise and vitamins C and E (VCE) supplementation can be beneficial to diabetes due to reducing blood glucose and free radical production. The aim of this study was to analyze the effect of moderate exercise with vitamin VCE on lipid peroxidation (LP) and antioxidative systems in the kidneys and lens of streptozotocin-induced diabetic rats. Forty female Wistar rats were used. They were randomly divided into four groups. The first and second groups were used as control and diabetic groups. The third group was the diabetic-exercise group. VCE-supplemented feed was given to diabetic-exercise rats constituting the fourth group. Animals in the exercised groups were moderately exercised daily on a treadmill for three weeks (five days a week). Diabetes was induced on day zero of exercise. Body weights in the four groups were recorded weekly. Lens and kidney samples were taken from all animals on day 20. Glutathione peroxidase (GSH-Px), reduced glutathione (GSH), vitamin E, and beta-carotene levels in kidney and lens, albumin in plasma, and body weight were significantly lower in the diabetic group than in the control group, whereas there was a significant increase in LP of kidney and lens as well as plasma glucose, urea, and creatinine levels in the diabetic group. The decrease in antioxidant enzymes, vitamins, and albumin and the increase in LP and glucose levels in diabetic rats were significantly improved with exercise and VCE supplementation. In the diabetic animals, the decreased beta-carotene and vitamins A levels in kidney did not improve through exercise only, although their levels were increased by exercise plus VCE supplementation. In conclusion, these data demonstrate that lipid peroxidation increases in the lens and kidney of diabetic animals and this could be due to decreases in antioxidant vitamins and enzymes. However, dietary VCE

  3. Oxidative Stress Parameters and Erythrocyte Membrane Adenosine Triphosphatase Activities in Streptozotocin-induced Diabetic Rats Administered Aqueous Preparation of Kalanchoe Pinnata Leaves

    PubMed Central

    Menon, Nikhil; Sparks, Jean; Omoruyi, Felix O.

    2016-01-01

    Background: Diabetes mellitus is a chronic metabolic disease that according to the World Health Organization affects more than 382 million people. The rise in diabetes mellitus coupled with the lack of an effective treatment has led many to investigate medicinal plants to identify a viable alternative. Objective: To evaluate red blood cell (RBC) membrane adenosine triphosphatase (ATPase) activities and antioxidant levels in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe pinnata leaves. Materials and Methods: Diabetes mellitus was induced in rats by a single administration of streptozotocin (60 mg/kg). Diabetic rats were then treated with aqueous K. pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14 g/kg body weight/day) for 30 days. Serum glucose, RBC membrane ATPase activities, and antioxidant levels were determined. Results: We noted weight loss and reduced food consumption in the treated diabetic group. Serum glucose levels were reduced in the treated diabetic group compared to the other groups. Superoxide dismutase activity and glutathione levels were not significantly elevated in the treated group compared to the diabetic group. However, serum catalase activity was significantly (P < 0.05) increased in the treated diabetic group compared to the other groups. Serum thiobarbituric acid reactive substances were not significantly altered among the groups. There was a significant (P < 0.05) increase in Mg2+ ATPase activity and a nonsignificant increase in Na+/K+ ATPase activity in the RBC membrane of the treated diabetic group compared to the diabetic group. Conclusion: The consumption of aqueous preparation of K. pinnata may accrue benefits in the management of diabetes by lowering oxidative stress often associated with the disease and improving the availability of cellular magnesium through an increase in the magnesium ATPase pump in the RBC membrane for increased cellular metabolism of glucose

  4. Antidiabetic assessment; in vivo study of gold and core-shell silver-gold nanoparticles on streptozotocin-induced diabetic rats.

    PubMed

    Shaheen, Th I; El-Naggar, Mehrez E; Hussein, Jihan S; El-Bana, Mona; Emara, Enayat; El-Khayat, Z; Fouda, Moustafa M G; Ebaid, Hossam; Hebeish, A

    2016-10-01

    Recently, we have published a pioneering work on green biosynthesis and complete characterization of gold and core shell silver-gold nanoparticles (AuNPs and Ag@AuNPs). Herein, the so obtained nanoparticles are assessed for their antidiabetic activity in streptozotocin-induced diabetic rats. Thus, sixty-four male albino rats were divided into eight groups: control untreated; diabetic rats; diabetic rats received standard drug; diabetic rats received carrier only; diabetic rats received 0.5ml AuNPs; diabetic rats received 1ml AuNPs; diabetic rats received 0.5ml Ag@AuNPs and diabetic rats received 1ml Ag@AuNPs for twenty-one days. Results revealed that diabetic rats treated with AuNPs or Ag@AuNPs restored normal glucose level. In particular, Ag@AuNPs was found to significantly induce a reduction in blood glucose and restore both the high serum insulin level and glucokinase activity compared to the control normal rats. The results obtained disclose the effectual role of Ag@AuNPs in reducing the lipid profile, an anti-inflammatory effect in diabetic rats assessed using inflammatory markers IL-α and C-reactive protein (CRP). Histopathological examination of diabetic rats signifies distortion in the arrangement of cells around the central vein, inflammatory cells, pyknotic and apoptotic nuclei. Kidney of diabetic rat appears with vacuolation and pyknotic nuclei of some tubules. On the other hand, the liver of diabetic rat treated with Ag@AuNPs displayed normal hepatic cells with only few necrosis of hepatocytes. Ag@AuNPs restored the increased number of caspase-3 stained cells in the liver and kidney tissue in diabetic rats. In conclusion, Ag@AuNPs was observed to improve diabetic condition by limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats which subsequently evoke the potential impact of AuNPs as a cost effective therapeutic cure in diabetic treatments and its complications.

  5. In vivo recovery effect of silibinin treatment on streptozotocin-induced diabetic mice is associated with the modulations of Sirt-1 expression and autophagy in pancreatic β-cell.

    PubMed

    Wang, Qiong; Liu, Miao; Liu, Wei-Wei; Hao, Wen-Bo; Tashiro, Shin-ichi; Onodera, Satoshi; Ikejima, Takashi

    2012-01-01

    Improper adjustments of autophagy and silent information regulator 1 (Sirt-1) expression were reported to be closely associated with metabolic disorders. In this study, we examined the roles of Sirt-1 and autophagy in streptozotocin-induced diabetes mellitus, assessed the relationship between autophagy and Sirt-1, and investigated the protective mechanism of silibinin. Diabetes was induced in 6-week-old mice by intravenous injection of streptozotocin (150 mg/kg/day, for 2 weeks). In the treatment groups, silibinin (50 mg/kg/day, intramuscular injection, for 8 weeks) or inhibitors (50 mg/kg/day, subcutaneous injection, for 8 weeks) were given. Diabetic control animals received vehicle for the same time. Compared with diabetic controls, silibinin or autophagy inhibitor, 3-methyladenine, treated mice showed decreased levels of glycosylated hemoglobin A1C (P < 0.01), serum triglyceride (P < 0.01), cholesterol (P < 0.01), blood glucose (P < 0.05), autophagy (P < 0.05), and apoptosis ratio (P < 0.05) of pancreatic β-cells. Systemic administration of silibinin reversed streptozotocin-induced downregulation of Sirt-1 expression. Sirt-1 may play a role in regulating the physiological level of autophagy and is associated with loss of pancreatic β-cells and metabolic biochemical disorders. Through promoting Sirt-1 expression and recovering autophagy physiologically, silibinin may reverse hyperglycemia and repair damaged pancreatic β-cells.

  6. [The influence of N-stearoylethanolamine on the activity of antioxidant enzymes and on the level of stable NO metabolites in the rat testes and blood plasma at the early stages of streptozotocine-induced diabetes].

    PubMed

    Gorid'ko, T M; Kosiakova, H V; Berdyshev, A H; Bazylians'ka, V R; Margitych, V M; Gula, N M

    2012-01-01

    The influence of N-stearoylethanolamine was investigated on the activity of enzymes of antioxidant protection and content of stable metabolites of nitric oxide (NO) in the testes and plasma of rats at the early stages of development of streptozotocine-induced diabetes mellitus. It was shown that the activity of superoxide dismutase, catalase is reduced in the plasma and testes of animals with streptozotocin-induced (50 mg/kg) diabetes (blood glucose 8-10 mmol/L). A significant increase in the amount of nitrite and nitrate anions was revealed in the plasma of rats, while only the level of nitrite was significantly changed in the testes of animals. The per os administration of the NSE aqueous suspension in a dose of 50 mg/kg during 10 days to the rats with induced diabetes contributed to the normalization of catalase activity in the testis, which correlated with a decrease in the amount of TBA-reacting products and activity of superoxide dismutase and catalase in the blood plasma of animals; the use of NSE also contributed to the reduction of nitrite content in the gonads and to normalization of both nitrite and nitrate in the blood plasma of rats. The NSE administration to intact animals caused an increase in superoxide dismutase activity and significantly reduced the content of stable NO metabolites in the blood plasma of animals.

  7. Polysaccharide from Angelica sinensis ameliorates high-fat diet and STZ-induced hepatic oxidative stress and inflammation in diabetic mice by activating the Sirt1-AMPK pathway.

    PubMed

    Wang, Kaiping; Tang, Zhuohong; Wang, Jinglin; Cao, Peng; Li, Qiang; Shui, Weizhi; Wang, Hongjing; Zheng, Ziming; Zhang, Yu

    2017-02-10

    Polysaccharide from Angelica sinensis (Oliv.) Diels (ASP) possesses many bioactivities, such as hematopoiesis, anti-inflammation, antioxidation and metabolism regulation. The aim of this study was to investigate the mechanisms underlying the protection of a combination of high-fat diet and streptozotocin-induced liver damage in diabetic Balb/c mice by ASP. Results showed that ASP had beneficial effects on ameliorating hyperglycemia, dyslipidemia and liver injury. Moreover, mechanistic study for the liver-protective role in vivo demonstrated that ASP enhanced the activities of superoxide dismutase and glutathione peroxidase and increased the glutathione content, which resulted in the reduction of hepatic reactive oxygen species (ROS) and malondialdehyde, and reduced the protein expression levels of liver IKKα/NF-κB/p-IκBα and the concentrations of serum tumor necrosis factor-α/interleukin-6. The antioxidative and anti-inflammatory actions of ASP might benefit from activating the Sirt1-AMPK signaling pathway. Furthermore, in vitro experiments using HepG2 cells treated with Sirt1 and AMPK inhibitors or small interfering RNA targeting Sirt1 confirmed that ASP suppressed the nuclear protein NF-κB p65 and intracellular ROS via the activation of Sirt1-AMPK signals. Collectively, ASP protects the liver against high-fat diet and streptozotocin-induced injury, which may contribute to the recovery of diabetic symptoms. Our findings strengthen the potential therapeutic role of ASP in nutritional foods or prescription for liver diseases or diabetes.

  8. Diazoxide preconditioning of endothelial progenitor cells from streptozotocin-induced type 1 diabetic rats improves their ability to repair diabetic cardiomyopathy.

    PubMed

    Ali, Muhammad; Mehmood, Azra; Anjum, Muhammad Sohail; Tarrar, Moazzam Nazir; Khan, Shaheen N; Riazuddin, Sheikh

    2015-12-01

    Type 1 diabetes mellitus (DM) is a strong risk factor for the development of diabetic cardiomyopathy (DCM) which is the leading cause of morbidity and mortality in the type 1 diabetic patients. Stem cells may act as a therapeutic agent for the repair of DCM. However, deteriorated functional abilities and survival of stem cells derived from type 1 diabetic subjects need to be overcome for obtaining potential outcome of the stem cell therapy. Diazoxide (DZ) a highly selective mitochondrial ATP-sensitive K(+) channel opener has been previously shown to improve the ability of mesenchymal stem cells for the repair of heart failure. In the present study, we evaluated the effects of DZ preconditioning in improving the ability of streptozotocin-induced type 1 diabetes affected bone marrow-derived endothelial progenitor cells (DM-EPCs) for the repair of DCM in the type 1 diabetic rats. DM-EPCs were characterized by immunocytochemistry, flow cytometry, and reverse transcriptase PCR for endothelial cell-specific markers like vWF, VE cadherin, VEGFR2, PECAM, CD34, and eNOS. In vitro studies included preconditioning of DM-EPCs with 200 μM DZ for 30 min followed by exposure to either 200 μM H2O2 for 2 h (for oxidative stress induction) or 30 mM glucose media (for induction of hyperglycemic stress) for 48 h. Non-preconditioned EPCs with and without exposure to H2O2 and 30 mM high glucose served as controls. These cells were then evaluated for survival (by MTT and XTT cell viability assays), senescence, paracrine potential (by ELISA for VEGF), and alteration in gene expression [VEGF, stromal derived factor-1α (SDF-1α), HGF, bFGF, Bcl2, and Caspase-3]. DZ preconditioned DM-EPCs demonstrated significantly increased survival and VEGF release while reduced cell injury and senescence. Furthermore, DZ preconditioned DM-EPCs exhibited up-regulated expression of prosurvival genes (VEGF, SDF-1α, HGF, bFGF, and Bcl2) on exposure to H2O2, and VEGF and Bcl2 on exposure to hyperglycemia

  9. Gugulipid, an extract of Commiphora whighitii with lipid-lowering properties, has protective effects against streptozotocin-induced memory deficits in mice.

    PubMed

    Saxena, Gunjan; Singh, Sheelendra Pratap; Pal, Raghvendra; Singh, Stayawan; Pratap, Ram; Nath, Chandishwar

    2007-04-01

    (ic) resulted into increase in AChE activity, low level of GSH and high concentration of MDA in brain on 21st day as compared to control. Gugulipid treatment caused significant decrease in AChE activity, low level of MDA and high concentration of GSH in brain following STZ (ic) as compared to vehicle administration in STZ (ic)-treated mice. The study demonstrated that gugulipid has significant protective affect against streptozotocin-induced memory deficits model of dementia that can be attributed to anti-oxidant and anti-AChE activity of gugulipid. These observations suggest gugulipid as a potential anti-dementia drug (CDRI, Lucknow has obtained US patent No. 6896901 for use of gugulipid as cognitive enhancer).

  10. Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine generation in the kidney of streptozotocin-induced diabetic rats by blocking advanced glycation end product-induced protein arginine methyltranferase-1 expression.

    PubMed

    Ojima, Ayako; Ishibashi, Yuji; Matsui, Takanori; Maeda, Sayaka; Nishino, Yuri; Takeuchi, Masayoshi; Fukami, Kei; Yamagishi, Sho-ichi

    2013-01-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, contributes to diabetic nephropathy. We have found that glucagon-like peptide-1 (GLP-1) inhibits the AGE-induced inflammatory reactions in endothelial cells. However, effects of GLP-1 on the AGE-RAGE-ADMA axis are unknown. This study examined the effects of GLP-1 on reactive oxygen species (ROS) generation, gene expression of protein arginine methyltransfetase-1 (PRMT-1), an enzyme that mainly generates ADMA, and ADMA levels in human proximal tubular cells. Streptozotocin-induced diabetic rats received continuous i.p. infusion of 0.3 μg of vehicle or 1.5 μg of the GLP-1 analog exendin-4 per kilogram of body weight for 2 weeks. We further investigated whether and how exendin-4 treatment reduced ADMA levels and renal damage in streptozotocin-induced diabetic rats. GLP-1 inhibited the AGE-induced RAGE and PRMT-1 gene expression, ROS, and ADMA generation in tubular cells, which were blocked by small-interfering RNAs raised against GLP-1 receptor. Exendin-4 treatment decreased gene expression of Rage, Prmt-1, Icam-1, and Mcp-1 and ADMA level; reduced urinary excretions of 8-hydroxy-2'-deoxyguanosine and albumin; and improved histopathologic changes of the kidney in diabetic rats. Our present study suggests that GLP-1 receptor agonist may inhibit the AGE-RAGE-mediated ADMA generation by suppressing PRMT-1 expression via inhibition of ROS generation, thereby protecting against the development and progression of diabetic nephropathy.

  11. The Antidiabetic Effect of Low Doses of Moringa oleifera Lam. Seeds on Streptozotocin Induced Diabetes and Diabetic Nephropathy in Male Rats

    PubMed Central

    Al-Malki, Abdulrahman L.; El Rabey, Haddad A.

    2015-01-01

    The antidiabetic activity of two low doses of Moringa seed powder (50 and 100 mg/kg body weight, in the diet) on streptozotocin (STZ) induced diabetes male rats was investigated. Forty rats were divided into four groups. The diabetic positive control (STZ treated) group showed increased lipid peroxide, increased IL-6, and decreased antioxidant enzyme in the serum and kidney tissue homogenate compared with that of the negative control group. Immunoglobulins (IgA, IgG), fasting blood sugar, and glycosylated hemoglobin (HbA1c) were also increased as a result of diabetes in G2 rats. Moreover albumin was decreased, and liver enzymes and α-amylase were not affected. In addition, the renal functions and potassium and sodium levels in G2 were increased as a sign of diabetic nephropathy. Urine analysis showed also glucosuria and increased potassium, sodium, creatinine, uric acid, and albumin levels. Kidney and pancreas tissues showed also pathological alteration compared to the negative control group. Treating the diabetic rats with 50 or 100 mg Moringa seeds powder/kg body weight in G3 and G4, respectively, ameliorated the levels of all these parameters approaching the negative control values and restored the normal histology of both kidney and pancreas compared with that of the diabetic positive control group. PMID:25629046

  12. The hydrogen sulfide releasing compounds ATB-346 and diallyl trisulfide attenuate streptozotocin-induced cognitive impairment, neuroinflammation, and oxidative stress in rats: involvement of asymmetric dimethylarginine.

    PubMed

    Mostafa, Dalia K; El Azhary, Nesrine M; Nasra, Rasha A

    2016-07-01

    Hydrogen sulfide (H2S) has attracted interest as a gaseous mediator involved in diverse processes in the nervous system, particularly with respect to learning and memory. However, its therapeutic potential in Alzheimer disease (AD) is not fully explored. Therefore, the effects of H2S-releasing compounds against AD-like behavioural and biochemical abnormalities were investigated. Memory deficit was induced by intracerberoventicular injection of streptozotocin (STZ, 3 mg·kg(-1)). Animals were randomly assigned into 5 groups (12 rats each): normal control, STZ treated, and 3 drug-treated groups receiving naproxen, H2S-releasing naproxen (ATB-346), and diallyl trisulfide in 20, 32, 40 mg·kg(-1)·day(-1), respectively. Memory function was assessed by passive avoidance and T-maze tasks. After 21 days, hippocampal IL-6, malondialdehyde, reduced glutathione (GSH), asymmetric dimethylarginine (ADMA), and acetylcholinestrase activity were determined. ATB-346 and diallyl trisulfide ameliorated behavioural performance and reduced malondialdehyde, ADMA, and acetylcholinestrase activity while increasing GSH. This study demonstrates the beneficial effects of H2S release in STZ-induced memory impairment by modulation of neuroinflammation, oxidative stress, and cholinergic function. It also delineates the implication of ADMA to the cognitive impairment induced by STZ. These findings draw the attention to H2S-releasing compounds as new candidates for treating neurodegenerative disorders that have prominent oxidative and inflammatory components such as AD.

  13. The antidiabetic effect of low doses of Moringa oleifera Lam. seeds on streptozotocin induced diabetes and diabetic nephropathy in male rats.

    PubMed

    Al-Malki, Abdulrahman L; El Rabey, Haddad A

    2015-01-01

    The antidiabetic activity of two low doses of Moringa seed powder (50 and 100 mg/kg body weight, in the diet) on streptozotocin (STZ) induced diabetes male rats was investigated. Forty rats were divided into four groups. The diabetic positive control (STZ treated) group showed increased lipid peroxide, increased IL-6, and decreased antioxidant enzyme in the serum and kidney tissue homogenate compared with that of the negative control group. Immunoglobulins (IgA, IgG), fasting blood sugar, and glycosylated hemoglobin (HbA1c) were also increased as a result of diabetes in G2 rats. Moreover albumin was decreased, and liver enzymes and α-amylase were not affected. In addition, the renal functions and potassium and sodium levels in G2 were increased as a sign of diabetic nephropathy. Urine analysis showed also glucosuria and increased potassium, sodium, creatinine, uric acid, and albumin levels. Kidney and pancreas tissues showed also pathological alteration compared to the negative control group. Treating the diabetic rats with 50 or 100 mg Moringa seeds powder/kg body weight in G3 and G4, respectively, ameliorated the levels of all these parameters approaching the negative control values and restored the normal histology of both kidney and pancreas compared with that of the diabetic positive control group.

  14. Autophagy ameliorates cognitive impairment through activation of PVT1 and apoptosis in diabetes mice.

    PubMed

    Li, Zhigui; Hao, Shuang; Yin, Hongqiang; Gao, Jing; Yang, Zhuo

    2016-05-15

    The underlying mechanisms of cognitive impairment in diabetes remain incompletely characterized. Here we show that the autophagic inhibition by 3-methyladenine (3-MA) aggravates cognitive impairment in streptozotocin-induced diabetic mice, including exacerbation of anxiety-like behaviors and aggravation in spatial learning and memory, especially the spatial reversal memory. Further neuronal function identification confirmed that both long term potentiation (LTP) and depotentiation (DPT) were exacerbated by autophagic inhibition in diabetic mice, which indicating impairment of synaptic plasticity. However, no significant change of pair-pulse facilitation (PPF) was recorded in diabetic mice with autophagic suppression compared with the diabetic mice, which indicated that presynaptic function was not affected by autophagic inhibition in diabetes. Subsequent hippocampal neuronal cell death analysis showed that the apoptotic cell death, but not the regulated necrosis, significantly increased in autophagic suppression of diabetic mice. Finally, molecular mechanism that may lead to cell death was identified. The long non-coding RNA PVT1 (plasmacytoma variant translocation 1) expression was analyzed, and data revealed that PVT1 was decreased significantly by 3-MA in diabetes. These findings show that PVT1-mediated autophagy may protect hippocampal neurons from impairment of synaptic plasticity and apoptosis, and then ameliorates cognitive impairment in diabetes. These intriguing findings will help pave the way for exciting functional studies of autophagy in cognitive impairment and diabetes that may alter the existing paradigms.

  15. Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates

    PubMed Central

    Zarei, Mahnaz; Fakher, Shima; Tabei, Seyed Mohammad Bagher; Javanbakht, Mohammad Hassan; Derakhshanian, Hoda; Farahbakhsh-Farsi, Payam; Sadeghi, Mohammad Reza; Mostafavi, Ebrahim; Djalali, Mahmoud

    2016-01-01

    INTRODUCTION This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications. PMID:26996784

  16. Antidiabetic Potentiality of the Aqueous-Methanolic Extract of Seed of Swietenia mahagoni (L.) Jacq. in Streptozotocin-Induced Diabetic Male Albino Rat: A Correlative and Evidence-Based Approach with Antioxidative and Antihyperlipidemic Activities

    PubMed Central

    De, Debasis; Chatterjee, Kausik; Ali, Kazi Monjur; Bera, Tushar Kanti; Ghosh, Debidas

    2011-01-01

    Antidiabetic, antioxidative, and antihyperlipidemic activities of aqueous-methanolic (2 : 3) extract of Swietenia mahagoni (L.) Jacq. (family Meliaceae) seed studied in streptozotocin-induced diabetic rats. Feeding with seed extract (25 mg 0.25 mL distilled water−1100 gm b.w.−1rat−1 day−1) for 21 days to diabetic rat lowered the blood glucose level as well as the glycogen level in liver. Moreover, activities of antioxidant enzymes like catalase, peroxidase, and levels of the products of free radicals like conjugated diene and thiobarbituric acid reactive substances in liver, kidney, and skeletal muscles were corrected towards the control after this extract treatment in this model. Furthermore, the seed extract corrected the levels of serum urea, uric acid, creatinine, cholesterol, triglyceride, and lipoproteins towards the control level in this experimental diabetic model. The results indicated the potentiality of the extract of S. mahagoni seed for the correction of diabetes and its related complications like oxidative stress and hyperlipidemia. The extract may be a good candidate for developing a safety, tolerable, and promising neutraceutical treatment for the management of diabetes. PMID:20981322

  17. Synthesis, Spectral Characterization, and Biochemical Evaluation of Antidiabetic Properties of a New Zinc-Diosmin Complex Studied in High Fat Diet Fed-Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats

    PubMed Central

    Gopalakrishnan, Veerasamy; Iyyam Pillai, Subramanian; Subramanian, Sorimuthu Pillai

    2015-01-01

    In view of the established antidiabetic properties of zinc, the present study was aimed at evaluating the hypoglycemic properties of a new zinc-diosmin complex in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Zinc-diosmin complex was synthesized and characterized by various spectral studies. The complexation between zinc ions and diosmin was further evidenced by pH-potentiometric titrations and Job's plot. Diabetic rats were orally treated with zinc-diosmin complex at a concentration of 20 mg/kg b.w./rat/day for 30 days. At the end of the experimental period, the rats were subjected to oral glucose tolerance test. In addition, HOMA-IR and various biochemical parameters related to glucose homeostasis were analyzed. Treatment with zinc-diosmin complex significantly improved the glucose homeostasis in diabetic rats. Treatment with zinc-diosmin complex significantly improved insulin sensitivity, at least in part, through enhancing protein metabolism and alteration in the levels of muscle and liver glycogen. The assay of clinical marker enzymes revealed the nontoxic nature of the complex. Determination of renal tissue markers such as blood urea and serum creatinine indicates the renoprotective nature of the complex. These findings suggest that zinc-diosmin complex is nontoxic and has complimentary potential to develop as an antihyperglycemic agent for the treatment of diabetes mellitus. PMID:26783461

  18. Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats.

    PubMed

    Kumar, Peeyush T; Antony, Sherin; Nandhu, Mohan S; Sadanandan, Jayanarayanan; Naijil, George; Paulose, Chiramadathikudiyil S

    2011-05-01

    Nutritional therapy is a challenging but necessary dimension in the management of diabetes and neurodegenerative changes associated with it. The study evaluates the effect of vitamin D(3) in preventing the altered function of cholinergic, insulin receptors and GLUT3 in the cerebral cortex of diabetic rats. Muscarinic M3 acetylcholine receptors in pancreas control insulin secretion. Vitamin D(3) treatment in M3 receptor regulation in the pancreatic islets was also studied. Radioreceptor binding assays and gene expression was done in the cerebral cortex of male Wistar rats. Immunocytochemistry of muscarinic M3 receptor was studied in the pancreatic islets using specific antibodies. Y-maze was used to evaluate the exploratory and spatial memory. Diabetes induced a decrease in muscarinic M1, insulin and vitamin D receptor expression and an increase in muscarinic M3, α7 nicotinic acetylcholine receptor, acetylcholine esterase and GLUT3 expression. Vitamin D(3) and insulin treatment reversed diabetes-induced alterations to near control. Diabetic rats showed a decreased Y-maze performance while vitamin D(3) supplementation improved the behavioural deficit. In conclusion, vitamin D(3) shows a potential therapeutic effect in normalizing diabetes-induced alterations in cholinergic, insulin and vitamin D receptor and maintains a normal glucose transport and utilisation in the cortex. In addition vitamin D(3) modulated muscarinic M3 receptors activity in pancreas and plays a pivotal role in controlling insulin secretion. Hence our findings proved, vitamin D(3) supplementation as a potential nutritional therapy in ameliorating diabetes mediated cortical dysfunctions and suggest an interaction between vitamin D(3) and muscarinic M3 receptors in regulating insulin secretion from pancreas.

  19. Garlic Attenuates Plasma and Kidney ACE-1 and AngII Modulations in Early Streptozotocin-Induced Diabetic Rats: Renal Clearance and Blood Pressure Implications

    PubMed Central

    Al-Qattan, Khaled K.; Jayasree, Divya; Ali, Muslim

    2016-01-01

    Raw garlic aqueous extract (GE) has ameliorative actions on the renin-angiotensin system in type-1 diabetes mellitus (DM); however its effects on plasma and kidney angiotensin I converting enzyme type-1 (ACE-1) and angiotensin II (AngII) require further elucidation. This study investigated the effect of GE on plasma and kidney ACE-1 and AngII concentrations and in relation to systemic and renal clearance indicators significant to blood pressure (BP) homeostasis in early streptozotocin- (STZ-) induced type-1 DM. Normal rats (n = 10) received 0.5 mL normal saline (NR/NS), diabetic rats (n = 10) received 0.5 mL NS (DR/NS), and treated diabetic rats (n = 10) received 50 mg/0.1 mL/100 g body weight GE (DR/GE) as daily intraperitoneal injections for 8 weeks. Compared to NR/NS, DR/NS showed a significant increase in plasma ACE-1 and AngII and conversely a decrease in kidney ACE-1 and AngII. These changes were associated with an increase in BP and clearance functions. Alternatively and compared to DR/NS, DR/GE showed normalization or attenuation in plasma and kidney ACE-1 and AngII. These GE induced rectifications were associated with moderation in BP elevation and renal clearance functions. Garlic attenuates modulations in plasma and kidney ACE-1 and AngII, in addition to BP and renal clearance function in type-1 DM. PMID:27293465

  20. Antidiabetic and Antihyperlipidemic Properties of a Triterpenoid Compound, Dehydroeburicoic Acid, from Antrodia camphorata in Vitro and in Streptozotocin-Induced Mice.

    PubMed

    Kuo, Yueh-Hsiung; Lin, Cheng-Hsiu; Shih, Chun-Ching

    2015-11-25

    The aim of this study was to examine the effects of dehydroeburicoic acid (TT) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were randomly divided into six groups and given orally by gavage TT (at three dosages), metformin (Metf), fenfibrate (Feno), or vehicle for 4 weeks. STZ-induced diabetic mice showed elevations in blood glucose levels (P < 0.001). TT treatment markedly decreased blood glucose levels by 42.6-46.5%. Moreover, STZ-induced diabetic mice displayed an increase in circulating triglyceride (TG) and total cholesterol (TC) levels (P < 0.001 and P < 0.01, respectively) but a decrease in blood insulin and adiponectin levels (P < 0.01 and P < 0.05, respectively). These substances are also reversed by TT treatment, indicating TT ameliorated diabetes and dyslipidemia. Membrane skeletal muscular expression levels of glucose transporter 4 (GLUT4) and expression levels of AMPK phosphorylation (phospho-AMPK) in both liver and skeletal muscle were reduced in STZ-induced diabetic mice, which normalized upon TT treatment and correction of hyperglycemia accompanied with a decrease in mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6 Pase), which was related to the inhibition of hepatic glucose production and attenuating diabetic state. In addition, TT also showed hypolipidemic effect by increasing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a) but decreasing expression levels of fatty acid synthase (FAS), which further contributed to a decrease in circulating TG levels. TT-treated mice displayed decreased SREBP2 mRNA levels and reduced blood TC levels. These findings strongly support that TT prevents diabetic and dyslipidemic states in STZ-induced diabetic mice evidenced by regulation of GLUT4, PPARα, FAS, and phosphorylation of AMPK.

  1. Angiotensin-(1-7) administration attenuates Alzheimer's disease-like neuropathology in rats with streptozotocin-induced diabetes via Mas receptor activation.

    PubMed

    Chen, Jin-Liang; Zhang, Dong-Ling; Sun, Yue; Zhao, Yu-Xing; Zhao, Ke-Xiang; Pu, Die; Xiao, Qian

    2017-03-27

    Diabetes mellitus (DM) is associated with cognitive deficits and an increased risk of Alzheimer's disease (AD). Recently, a newly identified heptapeptide of the renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)], was found to protect against brain damage. This study investigated the effects of Ang-(1-7) on diabetes-induced cognitive deficits. Sprague-Dawley rats were randomly divided into four groups. Diabetes was induced via single i.p. streptozotocin (STZ) injections. Ten weeks after diabetes induction, rats in each group received an intracerebral-ventricular (ICV) infusion of either vehicle, Ang-(1-7) alone, or Ang-(1-7)+A779 daily for two weeks. At the end of the study, Morris water maze (MWM) tests were performed to test cognitive functions before the rats were euthanized. Ang-(1-7) treatment significantly reduced escape latencies in diabetic rats in acquisition trials and markedly enhanced platform area crossing frequency and time spent in the target quadrant in probe trials (3.0±0.39 vs. 1.0±0.33, 39.39±1.11% vs. 25.62±3.07%, respectively, P<0.01). Ang-(1-7) treatment ameliorated damage to the ultrastructure of hippocampal synapses, reduced the expression of hippocampal phospho-tau at Ser396 (P<0.01), Ser404 (P<0.01) and Ser202/Thr205 (P<0.05), and decreased amyloid-β oligomer and both soluble and insoluble β-amyloid peptide 1-42 (Aβ 1-42) and Aβ 1-40 levels (P<0.01). These protective effects were significantly reversed by the co-administration of A779. These findings show that Ang-(1-7) is a promising therapeutic target for diabetes-induced cognitive impairment. The neuroprotective effects of Ang-(1-7) were mainly through Mas receptor (MasR) activation.

  2. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    PubMed Central

    Oguntibeju, Oluwafemi O.; Meyer, Samantha; Aboua, Yapo G.; Goboza, Mediline

    2016-01-01

    Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue. PMID:27403200

  3. Properties of Flavonoids Isolated from the Bark of Eysenhardtia polystachya and Their Effect on Oxidative Stress in Streptozotocin-Induced Diabetes Mellitus in Mice

    PubMed Central

    Garcia-Campoy, Abraham Heriberto; Muñiz-Ramirez, Alethia

    2016-01-01

    Six new flavonoids 2′,4′-dihydroxychalcone-6′-O-β-d-glucopyranoside (1), α,3,2′,4′-tetrahydroxy-4-methoxy-dihydrochalcone-3′-C-β-glucopyranosy-6′-O-β-d-glucopyranoside (2), 7-hydroxy-5,8′-dimethoxy-6′α-l-rhamnopyranosyl-8-(3-phenyl-trans-acryloyl)-1-benzopyran-2-one (3), 6′7-dihydroxy-5,8-dimethoxy-8(3-phenyl-trans-acryloyl)-1-benzopyran-2-one (4), 9-hydroxy-3,8-dimethoxy-4-prenylpterocarpan (5), and α,4,4′-trihydroxydihydrochalcone-2′-O-β-d-glucopyranoside (6) were isolated from bark of Eysenhardtia polystachya. Antidiabetic activity of compounds 1–5 in terms of their cellular antioxidant and free radical scavenging and also in streptozotocin- (STZ-) induced diabetic mice was evaluated on liver transaminases, lipid peroxidation, total bilirubin, total protein, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (CSH-Px), and glutathione reductase (GSH). Results indicated that 1–5 scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (∙OH), nitric oxide radicals (NO∙), superoxide anion radical (O2∙−), radical cation (ABTS∙+), and hydrogen peroxide (H2O2) radical, and protection against H2O2 induced BSA damage was also observed. Furthermore, 1–5 showed ability to decrease the oxidative stress in H9c2 cell. Diabetic mice present high levels of lipid peroxide, total protein, SGPT, SGOT, ALP, and TB. However, treatment of STZ-induced diabetes in mice with 1–5 reduced levels of these enzymes leading to protector effect of liver. In addition, with treatment with 1–5, increases in radical scavenging enzymes of CSH-Px, SOD, GSH, and CAT have also been observed in diabetic mice. The antioxidant properties of compounds 1–5 are a promising strategy for ameliorating therapeutic effects by avoiding disorders in the normal redox reactions in healthy cells which consequently could alleviate complications of diabetes. PMID:27668038

  4. Validation of the Antidiabetic and Hypolipidemic Effects of Clitocybe nuda by Assessment of Glucose Transporter 4 and Gluconeogenesis and AMPK Phosphorylation in Streptozotocin-Induced Mice

    PubMed Central

    Shih, Chun-Ching; Chen, Mei-Hsing; Lin, Cheng-Hsiu

    2014-01-01

    The study was designed to investigate the effects of extract of Clitocybe nuda (CNE) on type 1 diabetes mellitus and dyslipidemia in streptozotocin- (STZ-) induced diabetic mice. Diabetes was induced by injection of STZ. Diabetic mice were randomly divided into five groups and given orally CNE (C1: 0.2, C2: 0.5, and C3: 1.0 g/kg body weight) or metformin (Metf) or vehicle for 4 weeks. STZ induction decreased in the levels of insulin, body weight, and the weight of skeletal muscle, whereas the levels of blood glucose, hemoglobin nonenzymatically (percent HbA1c), and circulating triglyceride (P < 0.001, P < 0.001, and P < 0.01, resp.) were increased. CNE decreased the levels of blood glucose, HbA1c, and triglyceride levels, whereas it increased the levels of insulin and leptin compared with the vehicle-treated STZ group. STZ induction caused a decrease in the protein contents of skeletal muscular and hepatic phosphorylation of AMP-activated protein kinase (phospho-AMPK) and muscular glucose transporter 4 (GLUT4). Muscular phospho-AMPK contents were increased in C2-, C3-, and Metf-treated groups. CNE and Metf significantly increased the muscular proteins of GLUT4. Liver phospho-AMPK showed an increase in all CNE- and Metf-treated groups combined with the decreased hepatic glucose production by decreasing phosphenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and 11beta hydroxysteroid dehydroxygenase (11β-HSD1) gene, which contributed to attenuating diabetic state. The study indicated that the hypoglycemic properties of CNE were related to both the increased muscular glucose uptake and the reduction in hepatic gluconeogenesis. CNE exerts hypolipidemic effect by increasing gene expressions of peroxisome proliferator-activated receptor α (PPARα) and decreasing expressions of fatty acid synthesis, including acyl-coenzyme A: diacylglycerol acyltransferase (DGAT) 2. Therefore, amelioration of diabetic and dyslipidemic state by CNE in STZ

  5. (−)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice

    PubMed Central

    Jian, Jia-Ying; Shih, Chun-Ching

    2017-01-01

    acid synthesis and lipid accumulation within adipose tissue, and consequently, to lower triglyceride levels in liver, blood, and adipose tissue. Moreover, BB treatment not only displayed the activation Akt in liver tissue and skeletal muscle, but also in C2C12 myotube to cause an increase in phosphorylation of Akt in the absence of insulin. These results demonstrated that BB act as an activator of AMPK and /or regulation of insulin pathway (Akt), and the antioxidant activity within the pancreas. Therefore, BB treatment ameliorated the diabetic and dyslipidemic state in STZ-induced diabetic mice. PMID:28333970

  6. Effects of Hydro-alcoholic Extract from Arctium lappa L. (Burdock) Root on Gonadotropins, Testosterone, and Sperm Count and Viability in Male Mice with Nicotinamide/ Streptozotocin-Induced Type 2 Diabetes

    PubMed Central

    AHANGARPOUR, Akram; OROOJAN, Ali Akbar; HEIDARI, Hamid; GHAEDI, Ehsan; TAHERKHANI, Reza

    2015-01-01

    Background: Reproductive dysfunction is a complication of diabetes. Arctium lappa (burdock) root has hypoglycemic and antioxidative properties, which are traditionally used for treatment of impotence and sterility. Therefore, the aim of this study is to investigate the effects of its hydro alcoholic extract on gonadotropin, testosterone, and sperm parameters in nicotinamide/ streptozotocin-induced diabetic mice. Methods: In this experimental study, 56 adult male Naval Medical Research Institute (NMRI) mice (30–35 g) were randomly divided into seven groups: control, diabetes, diabetes + glibenclamide (0.25 mg/kg), diabetes + extract (200 or 300 mg/kg), and extract (200 or 300 mg/kg). Diabetes was induced with intraperitoneal injection of nicotinamide (NA) and streptozotocin (STZ). Twenty-four hours after the last extract and drug administration, serum samples, testes, and cauda epididymis were removed immediately for experimental assessment. Results: Body weight, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels, and sperm count (P < 0.05) and viability (P < 0.01) decreased in diabetic mice. Administration of glibenclamide significantly improved these reductions in diabetic animals (P < 0.05). However, the hydro alcoholic extract (300 mg/kg) enhanced sperm viability only in diabetic mice (P < 0.01). In addition, this dose of extract increased sperm count, LH, FSH, and testosterone in nondiabetic animals compared with the control group (P < 0.05). Conclusion: The results indicate that applied burdock root extract has anti-infertility effects in nondiabetic mice. Hence, this part of the A. lappa plant has an effect on the health of the reproductive system in order to improve diabetic conditions. PMID:26023292

  7. GLP-1(28-36) improves β-cell mass and glucose disposal in streptozotocin-induced diabetic mice and activates cAMP/PKA/β-catenin signaling in β-cells in vitro.

    PubMed

    Shao, Weijuan; Wang, Zhaoxia; Ip, Wilfred; Chiang, Yu-Ting; Xiong, Xiaoquan; Chai, Tuanyao; Xu, Catherine; Wang, Qinghua; Jin, Tianru

    2013-06-15

    Recent studies have demonstrated that the COOH-terminal fragment of the incretin hormone glucagon-like peptide-1 (GLP-1), a nonapeptide GLP-1(28-36)amide, attenuates diabetes and hepatic steatosis in diet-induced obese mice. However, the effect of this nonapeptide in pancreatic β-cells remains largely unknown. Here, we show that in a streptozotocin-induced mouse diabetes model, GLP-1(28-36)amide improved glucose disposal and increased pancreatic β-cell mass and β-cell proliferation. An in vitro investigation revealed that GLP-1(28-36)amide stimulates β-catenin (β-cat) Ser(675) phosphorylation in both the clonal INS-1 cell line and rat primary pancreatic islet cells. In INS-1 cells, the stimulation was accompanied by increased nuclear β-cat content. GLP-1(28-36)amide was also shown to increase cellular cAMP levels, PKA enzymatic activity, and cAMP response element-binding protein (CREB) and cyclic AMP-dependent transcription factor-1 (ATF-1) phosphorylation. Furthermore, GLP-1(28-36)amide treatment enhanced islet insulin secretion and increased the growth of INS-1 cells, which was associated with increased cyclin D1 expression. Finally, PKA inhibition attenuated the effect of GLP-1(28-36)amide on β-cat Ser(675) phosphorylation and cyclin D1 expression in the INS-1 cell line. We have thus revealed the beneficial effect of GLP-1(28-36)amide in pancreatic β-cells in vitro and in vivo. Our observations suggest that GLP-1(28-36)amide may exert its effect through the PKA/β-catenin signaling pathway.

  8. Efficacy of a single high dose versus multiple low doses of LLLT on wounded skin fibroblasts

    NASA Astrophysics Data System (ADS)

    Hawkins, Denise H.; Abrahamse, Heidi

    2007-07-01

    Background/purpose: In vivo studies have demonstrated that phototherapy accelerates wound healing in the clinical environment; however the exact mechanism is still not completely understood. The main focus of this study was to use in vitro laboratory results to establish an effective treatment regimen that may be practical and applicable to the clinical environment. This in vitro study aimed to compare the cellular responses of wounded fibroblasts following a single exposure of 5 J/cm2 or multiple exposures of low doses (2.5 J/cm2 or 5 J/cm2) on one day of the week to a single application of a higher dose (16 J/cm2) on day 1 and day 4. Methodology: Cellular responses to Helium-Neon (632.8 nm) laser irradiation were evaluated by measuring changes in cell morphology, cell viability, cell proliferation, membrane integrity and DNA damage. Results: Wounded cells exposed to 5 J/cm2 on day 1 and day 4 showed an increase in cell viability, increase in the release of bFGF, increase in cell density, decrease in ALP enzyme activity and decrease in caspase 3/7 activity indicating a stimulatory effect. Wounded cells exposed to three doses of 5 J/cm2 on day 1 showed a decrease in cell viability and cell proliferation and an increase in LDH cytotoxicity and DNA damage indicating an inhibitory effect. Conclusion: Results indicate that cellular responses are influenced by the combination of dose administered, number of exposures and time between exposures. Single doses administered with sufficient time between exposures is more beneficial to restoring cell function than multiple doses within a short period. Although this work confirms previous reports on the cumulative effect of laser irradiation it provides essential information for the initiation of in vivo clinical studies.

  9. Inhibition of central angiotensin converting enzyme ameliorates scopolamine induced memory impairment in mice: role of cholinergic neurotransmission, cerebral blood flow and brain energy metabolism.

    PubMed

    Tota, Santoshkumar; Nath, Chandishwar; Najmi, Abul Kalam; Shukla, Rakesh; Hanif, Kashif

    2012-06-15

    Evidences indicate that inhibition of central Renin angiotensin system (RAS) ameliorates memory impairment in animals and humans. Earlier we have reported involvement of central angiotensin converting enzyme (ACE) in streptozotocin induced neurodegeneration and memory impairment. The present study investigated the role of central ACE in cholinergic neurotransmission, brain energy metabolism and cerebral blood flow (CBF) in model of memory impairment induced by injection of scopolamine in mice. Perindopril (0.05 and 0.1 mg/kg, PO) was given orally for one week before administration of scopolamine (3mg/kg, IP). Then, memory function was evaluated by Morris water maze and passive avoidance tests. CBF was measured by laser Doppler flowmetry. Biochemical and molecular parameters were estimated after the completion of behavioral studies. Scopolamine caused impairment in memory which was associated with reduced CBF, acetylcholine (ACh) level and elevated acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level. Perindopril ameliorated scopolamine induced amnesia in both the behavioral paradigms. Further, perindopril prevented elevation of AChE and MDA level in mice brain. There was a significant increase in CBF and ACh level in perindopril treated mice. However, scopolamine had no significant effect on ATP level and mRNA expression of angiotensin receptors and ACE in cortex and hippocampus. But, perindopril significantly decreased ACE activity in brain without affecting its mRNA expression. The study clearly showed the interaction between ACE and cholinergic neurotransmission and beneficial effect of perindopril can be attributed to improvement in central cholinergic neurotransmission and CBF.

  10. Ameliorative effect of melatonin against increased intestinal permeability in diabetic rats: possible involvement of MLCK-dependent MLC phosphorylation.

    PubMed

    Yang, Xiaoping; Zou, Duobing; Tang, Songtao; Fan, Tingting; Su, Huan; Hu, Ruolei; Zhou, Qing; Gui, Shuyu; Zuo, Li; Wang, Yuan

    2016-05-01

    The increased intestinal permeability and functional impairment play an important role in type 2 diabetes (T2D), and melatonin may possess enteroprotection properties. Therefore, we used streptozotocin-induced diabetic rat model to investigate the regulation of intestinal permeability by melatonin. Rats were randomly divided into three groups, including control, diabetes mellitus (DM), and DM rats treated with melatonin. Melatonin was administered (10 mg/kg/day) by gavage for 24 weeks. The DM rats significantly increased the serum fasting blood glucose and lipid levels, which were alleviated by melatonin treatment. Importantly, the intestinal epithelial permeability was significantly increased in DM rats but was ameliorated following treatment with melatonin. These findings also indicated the expression of myosin light chain kinase (MLCK) and phosphorylation of MLC targeting subunit (MYPT) induced myosin light chain (MLC) phosphorylation level was markedly elevated in hyperglycemic and hyperlipidemic status. They were partly associated with down-regulated membrane type 1 and 2 (MT1 and MT2) expression, and up-regulated Rho-associated protein kinase (ROCK) expression and increased extracellular signal-regulated kinase (ERK) phosphorylation. However, the changes in target protein expression were reversed by melatonin. In conclusion, our results show melatonin beneficial effects on impaired intestinal epithelial permeability in T2D by suppressing ERK/MLCK- and ROCK/MCLP-dependent MLC phosphorylation.

  11. Sequence specificity of streptozotocin-induced mutations.

    PubMed Central

    Mack, S L; Fram, R J; Marinus, M G

    1988-01-01

    The isolation and characterization of streptozotocin (STZ)-induced mutations in the phage P22 mnt repressor gene is described. Cells carrying the plasmid-borne mnt gene were exposed to STZ to give 10-20 percent survival and at least an eleven-fold increase in mutation frequency. DNA sequence analysis showed that 50 of 51 STZ-induced mutations were GC to AT transitions, and one was an AT to GC transition. We have also compared the STZ mutational spectrum to that for N-methyl-N'-nitro-N-nitroso-guanidine (MNNG). There are sites in the mnt gene which are mutated only by STZ; only by MNNG, or by both agents. Sites at which only STZ induced GC to AT transition mutations occur were in sequences that are pyrimidine rich 5' to the mutated site and purine rich 3' to the mutated site. Induction of mutations by both STZ and MNNG should be considered to maximize the number of mutable sites. PMID:2972994

  12. Syzygium cumini ameliorates insulin resistance and β-cell dysfunction via modulation of PPAR, dyslipidemia, oxidative stress, and TNF-α in type 2 diabetic rats.

    PubMed

    Sharma, Ashok Kumar; Bharti, Saurabh; Kumar, Rajiv; Krishnamurthy, Bhaskar; Bhatia, Jagriti; Kumari, Santosh; Arya, Dharamvir Singh

    2012-01-01

    Syzygium cumini (SC) is well known for its anti-diabetic potential, but the mechanism underlying its amelioration of type 2 diabetes is still elusive. Therefore, for the first time, we investigated whether SC aqueous seed extract (100, 200, or 400 mg/kg) exerts any beneficial effects on insulin resistance (IR), serum lipid profile, antioxidant status, and/or pancreatic β-cell damage in high-fat diet / streptozotocin-induced (HFD-STZ) diabetic rats. Wistar albino rats were fed with HFD (55% of calories as fat) during the experiment to induce IR and on the 10th day were injected with STZ (40 mg/kg, i.p.) to develop type 2 diabetes. Subsequently, after confirmation of hyperglycemia on the 14th day (fasting glucose level > 13.89 mM), diabetic rats were treated with SC for the next 21 days. Diabetic rats showed increased serum glucose, insulin, IR, TNF-α, dyslipidemia, and pancreatic thiobarbituric acid-reactive substances with a concomitant decrease in β-cell function and pancreatic superoxide dismutase, catalase, and glutathione peroxidase antioxidant enzyme activities. Microscopic examination of their pancreas revealed pathological changes in islets and β-cells. These alterations reverted to near-normal levels after treatment with SC at 400 mg/kg. Moreover, hepatic tissue demonstrated increased PPARγ and PPARα protein expressions. Thus, our study demonstrated the beneficial effect of SC seed extract on IR and β-cell dysfunction in HFD-STZ-induced type 2 diabetic rats.

  13. Discovery of a novel class of targeted kinase inhibitors that blocks protein kinase C signaling and ameliorates retinal vascular leakage in a diabetic rat model.

    PubMed

    Grant, Stephan; Tran, Phong; Zhang, Qin; Zou, Aihua; Dinh, Dac; Jensen, Jordan; Zhou, Sue; Kang, Xiaolin; Zachwieja, Joseph; Lippincott, John; Liu, Kevin; Johnson, Sarah Ludlum; Scales, Stephanie; Yin, Chunfeng; Nukui, Seiji; Stoner, Chad; Prasanna, Ganesh; Lafontaine, Jennifer; Wells, Peter; Li, Hui

    2010-02-10

    Protein kinase C (PKC) family members such as PKCbetaII may become activated in the hyperglycemic state associated with diabetes. Preclinical and clinical data implicate aberrant PKC activity in the development of diabetic microvasculature abnormalities. Based on this potential etiological role for PKC in diabetic complications, several therapeutic PKC inhibitors have been investigated in clinical trials for the treatment of diabetic patients. In this report, we present the discovery and preclinical evaluation of a novel class of 3-amino-pyrrolo[3,4-c]pyrazole derivatives as inhibitors of PKC that are structurally distinct from the prototypical indolocarbazole and bisindolylmaleimide PKC inhibitors. From this pyrrolo-pyrazole series, several compounds were identified from biochemical assays as potent, ATP-competitive inhibitors of PKC activity with high specificity for PKC over other protein kinases. These compounds were also found to block PKC signaling activity in multiple cellular functional assays. PF-04577806, a representative from this series, inhibited PKC activity in retinal lysates from diabetic rats stimulated with phorbol myristate acetate. When orally administered, PF-04577806 showed good exposure in the retina of diabetic Long-Evans rats and ameliorated retinal vascular leakage in a streptozotocin-induced diabetic rat model. These novel PKC inhibitors represent a promising new class of targeted protein kinase inhibitors with potential as therapeutic agents for the treatment of patients with diabetic microvascular complications.

  14. Aqueous Extract from Hibiscus sabdariffa Linnaeus Ameliorate Diabetic Nephropathy via Regulating Oxidative Status and Akt/Bad/14-3-3γ in an Experimental Animal Model

    PubMed Central

    Wang, Shou-Chieh; Lee, Shiow-Fen; Wang, Chau-Jong; Lee, Chao-Hsin; Lee, Wen-Chin; Lee, Huei-Jane

    2011-01-01

    Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract of Hibiscus sabdariffa L. (HSE) has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects of Hibiscus sabdariffa L. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glutathione activities significantly in diabetic kidney, and decreasing the plasma levels of triglyceride, low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL) value. In histological examination, HSE improves hyperglycemia-caused osmotic diuresis in renal proximal convoluted tubules (defined as hydropic change) in diabetic rats. The study also reveals that up-regulation of Akt/Bad/14-3-3γ and NF-κB-mediated transcription might be involved. In conclusion, our results show that HSE possesses the potential effects to ameliorate diabetic nephropathy via improving oxidative status and regulating Akt/Bad/14-3-3γ signaling. PMID:19965962

  15. Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway.

    PubMed

    Gandhi, Gopalsamy Rajiv; Jothi, Gnanasekaran; Antony, Poovathumkal James; Balakrishna, Kedike; Paulraj, Michael Gabriel; Ignacimuthu, Savarimuthu; Stalin, Antony; Al-Dhabi, Naif Abdullah

    2014-12-15

    In this study, the therapeutic efficacy of gallic acid from Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans was examined against high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats. Molecular-dockings were done to determine the putative binding modes of gallic acid into the active sites of key insulin-signaling markers. Gallic acid (20 mg/kg) given to high-fat diet fed-streptozotocin-induced rats lowered body weight gain, fasting blood glucose and plasma insulin in diabetic rats. It further restored the alterations of biochemical parameters to near normal levels in diabetic treated rats along with cytoprotective action on pancreatic β-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPARγ expressions in the liver and skeletal muscle. Consequently, it improved insulin-dependent glucose transport in adipose tissue through translocation and activation of glucose transporter protein 4 (GLUT4) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt) dependent pathway. Gallic acid docked with PPARγ; it exhibited promising interactions with the GLUT4, glucose transporter protein 1 (GLUT1), PI3K and p-Akt. These findings provided evidence to show that gallic acid could improve adipose tissue insulin sensitivity, modulate adipogenesis, increase adipose glucose uptake and protect β-cells from impairment. Hence it can be used in the management of obesity-associated type 2 diabetes mellitus.

  16. Application of GC/MS-based metabonomic profiling in studying the therapeutic effects of Huangbai-Zhimu herb-pair (HZ) extract on streptozotocin-induced type 2 diabetes in mice.

    PubMed

    Song, Lili; Liu, Hongyue; Wang, Yan; Wang, Yuming; Liu, Jinbiao; Zhou, Zhensheng; Chu, Huilun; Zhuang, Pengwei; Zhang, Yanjun

    2015-08-01

    A protocol for metabolic profiling of mice urine was developed based on gas chromatograph-mass spectrometer (GC-MS) to explore metabolic state directly. The intra-day, inter-day, repeatability, and stability RSD for most endogenous compounds were less than 3%. Type 2 diabetic mellitus (T2DM) mice model was induced by high calorie diet combined with streptozocin. Urine from the control, T2DM and Huangbai-Zhimu herb-pair (HZ) treatment mice were enrolled in the subsequent study to show the usefulness of the method. OPLS-DA scores plots demonstrate that the cluster of T2DM mice is separated from that of control mice, while HZ-T2DM mice are located close to control mice, indicating that metabolic profiles of these HZ-T2DM mice are placed toward those of control group. The results illustrate that HZ treatment could lower the level of d-glucose, hexadecanoic acid, octadecanoic acid, propanoic acid, 3-hydroxybutyric acid, and 2,3-dihydroxybutanoic acid in urine of DM mice, meanwhile the results show that HZ treatment could ameliorate T2DM symptoms by intervening the fatty acid metabolism, starch and sucrose metabolism, and glyoxylate and dicarboxylate metabolism. This preliminary application indicated that the method is suitable and reliable for urine metabolic profiling. This study might explain the metabolic effects of T2DM and the mechanisms of action of HZ against T2DM.

  17. Ellagic acid and gingerol, activators of the sarco-endoplasmic reticulum Ca²⁺-ATPase, ameliorate diabetes mellitus-induced diastolic dysfunction in isolated murine ventricular myocardia.

    PubMed

    Namekata, Iyuki; Hamaguchi, Shogo; Wakasugi, Yumi; Ohhara, Minato; Hirota, Yoshitaka; Tanaka, Hikaru

    2013-04-15

    The effects of sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) activators, ellagic acid and gingerol, on the contraction and Ca(2+) transient were examined in isolated myocardia from streptozotocin-induced diabetic mice and compared with control mice. The time required for relaxation of the right ventricular free wall was significantly longer in streptozotocin-treated mice. The basal Ca(2+) concentration of isolated ventricular myocytes from streptozotocin-treated mice was significantly higher than those from control mice. The Ca(2+) transient decay rate was significantly lower in myocytes from streptozotocin-treated mice. Cyclopiazonic acid, a SERCA inhibitor, decreased the rate of relaxation and the rate of Ca(2+) transient decay; these effects were larger in control mice. Both ellagic acid and gingerol accelerated the rate of relaxation and the rate of Ca(2+) transient decay; these effects were larger in the streptozotocin-treated mice. The acceleration of relaxation by ellagic acid and gingerol was completely inhibited by cyclopiazonic acid. These results suggest that the diabetes mellitus-induced myocardial diastolic dysfunction is partly caused by reduction of SERCA function and can be ameliorated by SERCA activators.

  18. Dietary Amelioration of Helicobacter Infection

    PubMed Central

    Fahey, Jed W.; Stephenson, Katherine K.; Wallace, Alison J.

    2015-01-01

    We review herein the basis for using dietary components to treat and/or prevent Helicobacter pylori infection, with emphasis on: (a) work reported in the last decade, (b) dietary components for which there is mechanism-based plausibility, and (c) components for which clinical results on H. pylori amelioration are available. There is evidence that a diet-based treatment may reduce the levels and/or the virulence of H. pylori colonization without completely eradicating the organism in treated individuals. This concept was endorsed a decade ago by the participants in a small international consensus conference held in Honolulu, Hawaii, USA, and interest in such a diet-based approach has increased dramatically since then. This approach is attractive in terms of cost, treatment, tolerability and cultural acceptability. This review therefore highlights specific foods, food components, and food products, grouped as follows: bee products (e.g. honey and propolis), probiotics, dairy products, vegetables, fruits, oils, essential oils, and herbs, spices and other plants. A discussion of the small number of clinical studies that are available is supplemented by supportive in vitro and animal studies. This very large body of in vitro and pre-clinical evidence must now be followed up with rationally designed, unambiguous human trials. PMID:25799054

  19. Adriamycin cardiotoxicity amelioration by alpha-tocopherol.

    PubMed

    Krivit, W

    1979-01-01

    Adriamycin has become a potent member of the cancer chemotherapeutic program. However, the full utilization of adriamycin is limited by its cardiotoxicity. In experimental animals, alpha-tocopherol has been shown by some to ameliorate or prevent cardiac dysfunction without impairing antitumor effectiveness. During adriamycin therapy, future clinical research should consist of biochemical measurements of vitamin E in plasma, lipoperoxidation in red cells and platelets, while cars to indicate deficiency, should be considered as one method of ameliorating toxicity.

  20. SIRT1 activator ameliorates the renal tubular injury induced by hyperglycemia in vivo and in vitro via inhibiting apoptosis.

    PubMed

    Wang, Xue-Ling; Wu, Li-Yan; Zhao, Long; Sun, Li-Na; Liu, Hai-Ying; Liu, Gang; Guan, Guang-Ju

    2016-10-01

    We aimed to explore the role of SIRT1 in apoptosis in human kidney proximal tubule epithelial (HK-2) cells, and to determine whether resveratrol (RSV, a SIRT1 activator) could ameliorate apoptosis in rats with streptozotocin-induced diabetes mellitus (DM) and/or in high glucose (HG, 30mM) - stimulated HK-2 cells. Rats were distributed randomly into three groups: 1) control group, 2) DM group, and 3) DM with RSV group (DM+RSV; rats treated with 30mg/kg/d of RSV for 16 weeks). The physical, biochemical, and morphological parameters were then examined. Additionally, the deacetylase activity of SIRT1, and the expression levels of SIRT1 and of representative apoptosis markers, such as p53, acetylated p53, cleaved caspase-3, caspase-9, and cleaved PARP, were measured. HK-2 cells were stimulated by HG for different lengths of time to study the effect of HG on apoptosis. HK-2 cells were treated with or without RSV (25μM) to investigate if RSV has a protective effect on HG-induced apoptosis. A gene-specific small interfering RNA against SIRT1 was used to study the role of SIRT1 in apoptosis. More apoptosis was found in the DM rats than in the control rats. Similarly, the expression levels of cleaved caspase-3, cleaved PARP, and acetylated p53 were significantly higher, and the level of SIRT1 was significantly lower, in the HK-2 cells that were cultured under HG conditions than those in the HK-2 cells that were cultured under low glucose (5.5mM) conditions. Notably, treatment with RSV lessened the HG-induced changes in the levels of apoptosis indicators, and this inhibition of HG-induced apoptosis in HK-2 cells by RSV treatment was abolished by SIRT1 silencing. Our study showed that hyperglycemia contributes to apoptosis in rat kidney and HK-2 cells. SIRT1 activation by RSV can reduce urinary albumin excretion and proximal tubule epithelial apoptosis both in vitro and in vivo. Based on our study, SIRT1/p53 axis played an important role in the hyperglycemia induced apoptosis

  1. Fucoidan Extracts Ameliorate Acute Colitis.

    PubMed

    Lean, Qi Ying; Eri, Rajaraman D; Fitton, J Helen; Patel, Rahul P; Gueven, Nuri

    2015-01-01

    Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy) and depyrogenated fucoidan (DPF) was evaluated in the dextran sulphate sodium (DSS) mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF) or intraperitoneal administration (DPF). Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could therefore represent

  2. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Li; Deng, Yuanxiong; Yu, Sen; Lu, Shousi; Xie, Lin; Liu, Xiaodong

    2008-05-01

    Previous studies demonstrated anti-diabetic effects of berberine. However, the facts that berberine had low bioavailability and poor absorption through the gut wall indicated that berberine might exert its antihyperglycaemic effect in the intestinal tract before absorption. The purpose of this study was to investigate whether berberine attenuates disaccharidase activities and beta-glucuronidase activity in the small intestine of streptozotocin (STZ)-induced diabetic rats. Two groups of STZ-induced diabetic rats were treated with protamine zinc insulin (10 U/Kg) subcutaneously twice daily and berberine (100 mg/Kg) orally once daily for 4 weeks, respectively. Both age-matched normal rats and diabetic control rats received physiological saline only. Fasting blood glucose levels, body weight, intestinal disaccharidase and beta-glucuronidase activities in duodenum, jejunum and ileum were assessed for changes. Our findings suggested that berberine treatment significantly decreases the activities of intestinal disaccharidases and beta-glucuronidase in STZ-induced diabetic rats. The results demonstrated that the inhibitory effect on intestinal disaccharidases and beta-glucuronidase of berberine might be one of the mechanisms for berberine as an antihyperglycaemic agent.

  3. Subhuman Primate Pregnancy Complicated by Streptozotocin-Induced Diabetes Mellitus

    PubMed Central

    Mintz, Daniel H.; Chez, Ronald A.; Hutchinson, Donald L.

    1972-01-01

    Polydipsia, polyuria, polyphagia, and glucosuria followed the administration of streptozotocin to 6 nonpregnant and 15 pregnant monkeys (Macaca mulatta) in the first trimester of pregnancy. The diabetogenic action of the drug was also reflected in an induced but variable deterioration in maternal intravenous glucose tolerance and a marked attenuation of maternal plasma insulin responsiveness to intravenous glycemic stimuli. The products of conception were examined in 29 pregnancies. The neonates and the placentas of the streptozotocin-treated pregnant animals were significantly heavier than average for the period of gestation, polyhydramnios was consistently present, and there was an increase in the incidence of third trimester stillbirths. The fetal and maternal plasma glucose, insulin, and growth hormone concentrations were examined after the intravascular administration of glucose or a solution of mixed amino acids to the fetus in the third trimester. The neonatal plasma responses to similar insulinogenic stimuli were also examined. Fetal and neonatal base line plasma insulin concentrations were significantly elevated compared to those of the controls. The administration of intravascular glucose to the fetus, mother, or neonate was associated with a prompt 2-to 5-fold increase in fetal or neonatal plasma insulin concentrations. These findings contrast to the unresponsiveness of the pancreatic islet tissue we reported in normal subhuman primate pregnancy. The intravascular infusion of a relatively low concentration of mixed amino acids (2 mg/min) to the conceptii from the streptozotocin-treated pregnancies was associated with an elevation in fetal and neonatal plasma insulin levels, whereas normal monkey fetuses and neonates required a 10-fold greater concentration of amino acids in the infusate for similar responses. The induced hyperaminoacidemia or hyperglycemia did not consistently alter plasma growth hormone concentrations in the conceptii from normal or streptozotocin-treated pregnancies. These data provide evidence that maternal glucose intolerance during pregnancy is associated with enhanced fetal and neonatal pancreatic islet cell responsiveness to glucose and mixed amino acids. Although the specific mechanism(s) that alters both the sensitivity and responsiveness of the normal pancreatic fetal islet to insulinogenic stimuli remains unclear, the data do indicate that insulin-dependent maternal hyperglycemia and hyperaminoacidemia, separately or in combination could contribute to the fetal hyperinsulinemia of pregnancies complicated by diabetes mellitus. Moreover, the overall experiences with these streptozotocin-treated animals suggest that a subhuman primate model may be available to examine directly the antenatal pathophysiology of abnormal carbohydrate metabolism. PMID:4259254

  4. Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

    SciTech Connect

    Kang, Seong-Il; Jin, Young-Jun; Ko, Hee-Chul; Choi, Soo-Youn; Hwang, Joon-Ho; Whang, Ilson; Kim, Moo-Han; Shin, Hye-Sun; Jeong, Hyung-Bok; Kim, Se-Jae

    2008-08-22

    The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPAR{gamma} luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.

  5. Timing behavior in streptozotocin-induced diabetic rats.

    PubMed

    Orduña, Vladimir; Hong, Enrique; Bouzas, Arturo

    2011-10-10

    There is evidence of deterioration of spatial cognition in streptozotocin (STZ)-induced diabetic rats. Here, we evaluate a possible dissociation in the cognitive deficits due to diabetes by examining another crucial aspect of animal cognition: temporal perception. Timing behavior and temporal memory were evaluated in STZ-induced diabetic rats employing two timing tasks: the peak-interval procedure, with its Gap variant, and the interval bisection task. A spatial memory task, rewarded alternation in the T-maze, was also evaluated to explore spatial cognition. The two timing tasks employed coincide in the finding of a normal timing performance in STZ-induced diabetic rats. The peak-interval procedure provided results that suggest that the timing behavior is equally accurate and precise than in control subjects; in the Gap procedure, an equal change in peak time in both groups indicates that temporal working memory is also intact. In the interval bisection task, we analyzed the acquisition of a temporal discrimination and the sensitivity to changes in the duration of the stimulus; no differences were found in either the acquisition process or the sensitivity index. In contrast, in the rewarded alternation task, STZ-induced diabetic rats exhibited a significant deficit in spatial cognition. The cognitive processes involved in timing behavior and temporal memory are not deteriorated as a consequence of diabetes; the cognitive deficits associated to diabetes thus seem to be restricted to the spatial domain.

  6. Proteoglycans in bones of streptozotocin-induced diabetic rats.

    PubMed

    Perez, C; Suarez, C; Kofoed, J

    1990-01-01

    Insulin seems to regulate the biosynthesis of proteoglycans in some tissues such as growth plate and glomeruli. The present investigation was undertaken to assess the ex vivo influence of insulin on proteoglycan metabolism in bones. Mandible and femur bones were used. Xiphoid cartilage was used as a control tissue of high glycosaminoglycan content. Diabetes was induced by 0.12 mg/g b.w. streptozotocin in male Sprague-Dawley rats, a number of which was treated with insulin (1 I.U./100 g b.w.) for 6 days. As compared with control animals, diabetic rats exhibited a decreased [35S]sulfate uptake as well as a shift to the right in Sephacryl S-500 chromatography. In addition, they showed lower density of proteoglycans in sucrose gradient and shorter glycosaminoglycan side chains in Sephadex G-200 chromatography. These changes were partly reversed by insulin.

  7. Streptozotocin-Induced Diabetic Models in Mice and Rats.

    PubMed

    Furman, Brian L

    2015-09-01

    Streptozotocin (STZ) is an antibiotic that produces pancreatic islet β-cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this unit are protocols for producing STZ-induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition.

  8. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.

    PubMed

    Jin, Heung Yong; Lee, Kyung Ae; Song, Sun Kyung; Liu, Wei Jing; Choi, Ji Hae; Song, Chang Ho; Baek, Hong Sun; Park, Tae Sun

    2012-01-15

    We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy.

  9. Ethanol extract of mango (Mangifera indica L.) peel inhibits α-amylase and α-glucosidase activities, and ameliorates diabetes related biochemical parameters in streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Gondi, Mahendranath; Prasada Rao, U J S

    2015-12-01

    Peel is a major by-product during processing of mango fruit into pulp. Recent report indicates that the whole peel powder ameliorated diabetes. In the present study, ethanolic extract of mango peel was analysed for its bioactive compounds, evaluated for α-amylase and α-glucosidase inhibitory properties, oral glucose tolerance test, antioxidant properties, plasma insulin level and biochemical parameters related to diabetes. In addition to gallic and protocatechuic acids, the extract also had chlorogenic and ferulic acids, which were not reported earlier in mango peel extracts. The peel extract inhibited α-amylase and α-glucosidase activities, with IC50 values of 4.0 and 3.5 μg/ml. Ethanolic extract of peel showed better glucose utilization in oral glucose tolerance test. Treatment of streptozotocin-induced diabetic rats with the extract decreased fasting blood glucose, fructosamine and glycated hemoglobin levels, and increased plasma insulin level. Peel extract treatment decreased malondialdehyde level, but increased the activities of antioxidant enzymes significantly in liver and kidney compared to diabetic rats. These beneficial effects were comparable to metformin, but better than gallic acid treated diabetic rats. The beneficial effects of peel extract may be through different mechanism like increased plasma insulin levels, decreased oxidative stress and inhibition of carbohydrate hydrolyzing enzyme activities by its bioactive compounds. Thus, results suggest that the peel extract can be a potential source of nutraceutical or can be used in functional foods and this is the first report on antidiabetic properties of mango peel extract.

  10. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... OF THE TREASURY ALCOHOL WINE Production of Wine § 24.178 Amelioration. (a) General. In producing natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust..., during and after fermentation. The fixed acid level of the juice is determined prior to fermentation...

  11. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... OF THE TREASURY LIQUORS WINE Production of Wine § 24.178 Amelioration. (a) General. In producing natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust..., during and after fermentation. The fixed acid level of the juice is determined prior to fermentation...

  12. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... OF THE TREASURY LIQUORS WINE Production of Wine § 24.178 Amelioration. (a) General. In producing natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust..., during and after fermentation. The fixed acid level of the juice is determined prior to fermentation...

  13. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... OF THE TREASURY LIQUORS WINE Production of Wine § 24.178 Amelioration. (a) General. In producing natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust..., during and after fermentation. The fixed acid level of the juice is determined prior to fermentation...

  14. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... OF THE TREASURY ALCOHOL WINE Production of Wine § 24.178 Amelioration. (a) General. In producing natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust..., during and after fermentation. The fixed acid level of the juice is determined prior to fermentation...

  15. Calcium ameliorates diarrhea in immune compromised children

    PubMed Central

    Cheng, Sam X.; Bai, Harrison X.; Gonzalez-Peralta, Regino; Mistry, Pramod K.; Gorelick, Fred S.

    2015-01-01

    Treatment of infectious diarrheas remains a challenge, particularly in immunocompromised patients in whom infections usually persist and resultant diarrhea is often severe and protracted. Children with infectious diarrhea who become dehydrated are normally treated with oral or intravenous rehydration therapy. Although rehydration therapy can replace the loss of fluid, it does not ameliorate diarrhea. Thus, over the past decades, there has been continuous effort to search for ways to safely stop diarrhea. Herein, we report three cases of immunocompromised children who developed severe and/or protracted infectious diarrhea. Their diarrheas were successfully “halted” within 1-2 days following the administration of calcium. PMID:23343935

  16. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    PubMed

    Zempo, Hirofumi; Suzuki, Jun-ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress.

  17. Means for limiting and ameliorating electrode shorting

    DOEpatents

    Van Konynenburg, Richard A.; Farmer, Joseph C.

    1999-01-01

    A fuse and filter arrangement for limiting and ameliorating electrode shorting in capacitive deionization water purification systems utilizing carbon aerogel, for example. This arrangement limits and ameliorates the effects of conducting particles or debonded carbon aerogel in shorting the electrodes of a system such as a capacitive deionization water purification system. This is important because of the small interelectrode spacing and the finite possibility of debonding or fragmentation of carbon aerogel in a large system. The fuse and filter arrangement electrically protect the entire system from shutting down if a single pair of electrodes is shorted and mechanically prevents a conducting particle from migrating through the electrode stack, shorting a series of electrode pairs in sequence. It also limits the amount of energy released in a shorting event. The arrangement consists of a set of circuit breakers or fuses with one fuse or breaker in the power line connected to one electrode of each electrode pair and a set of screens of filters in the water flow channels between each set of electrode pairs.

  18. Multiple low-dose infusions of human umbilical cord blood cells improve cognitive impairments and reduce amyloid-β-associated neuropathology in Alzheimer mice.

    PubMed

    Darlington, Donna; Deng, Juan; Giunta, Brian; Hou, Huayan; Sanberg, Cyndy D; Kuzmin-Nichols, Nicole; Zhou, Hua-Dong; Mori, Takashi; Ehrhart, Jared; Sanberg, Paul R; Tan, Jun

    2013-02-01

    Alzheimer's disease (AD) is the most common progressive age-related dementia in the elderly and the fourth major cause of disability and mortality in that population. The disease is pathologically characterized by deposition of β-amyloid plaques neurofibrillary tangles in the brain. Current strategies for the treatment of AD are symptomatic only. As such, they are less than efficacious in terms of significantly slowing or halting the underlying pathophysiological progression of the disease. Modulation by cell therapy may be new promising disease-modifying therapy. Recently, we showed reduction in amyloid-β (Aβ) levels/β-amyloid plaques and associated astrocytosis following low-dose infusions of mononuclear human umbilical cord blood cells (HUCBCs). Our current study extended our previous findings by examining cognition via (1) the rotarod test, (2) a 2-day version of the radial-arm water maze test, and (3) a subsequent observation in an open pool platform test to characterize the effects of monthly peripheral HUCBC infusion (1×10(6) cells/μL) into the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) from 6 to 12 months of age. We show that HUCBC therapy correlates with decreased (1) cognitive impairment, (2) Aβ levels/β-amyloid plaques, (3) amyloidogenic APP processing, and (4) reactive microgliosis after a treatment of 6 or 10 months. As such, this report lays the groundwork for an HUCBC therapy as potentially novel alternative to oppose AD at the disease-modifying level.

  19. Multiple Low-Dose Radiation Prevents Type 2 Diabetes-Induced Renal Damage through Attenuation of Dyslipidemia and Insulin Resistance and Subsequent Renal Inflammation and Oxidative Stress

    PubMed Central

    Shao, Minglong; Lu, Xuemian; Cong, Weitao; Xing, Xiao; Tan, Yi; Li, Yunqian; Li, Xiaokun; Jin, Litai; Wang, Xiaojie; Dong, Juancong; Jin, Shunzi; Zhang, Chi; Cai, Lu

    2014-01-01

    Background Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress. Objective The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. Methods Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured. Results HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks. Conclusion These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress. PMID:24651118

  20. ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO

    EPA Science Inventory

    Antioxidant amelioration of arsenical-induced effects in vivo. ES Hunter and EH Rogers. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC.

    Antioxidants have been reported to ameliorate the effects of many developmental toxicants. We tested the hypothesis that oxi...

  1. Ameliorated GA approach for base station planning

    NASA Astrophysics Data System (ADS)

    Wang, Andong; Sun, Hongyue; Wu, Xiaomin

    2011-10-01

    In this paper, we aim at locating base station (BS) rationally to satisfy the most customs by using the least BSs. An ameliorated GA is proposed to search for the optimum solution. In the algorithm, we mesh the area to be planned according to least overlap length derived from coverage radius, bring into isometric grid encoding method to represent BS distribution as well as its number and develop select, crossover and mutation operators to serve our unique necessity. We also construct our comprehensive object function after synthesizing coverage ratio, overlap ratio, population and geographical conditions. Finally, after importing an electronic map of the area to be planned, a recommended strategy draft would be exported correspondingly. We eventually import HongKong, China to simulate and yield a satisfactory solution.

  2. Neuronal dysfunction with aging and its amelioration.

    PubMed

    Ando, Susumu

    2012-01-01

    The author focused on the functional decline of synapses in the brain with aging to understand the underlying mechanisms and to ameliorate the deficits. The first attempt was to unravel the neuronal functions of gangliosides so that gangliosides could be used for enhancing synaptic activity. The second attempt was to elicit the neuronal plasticity in aged animals through enriched environmental stimulation and nutritional intervention. Environmental stimuli were revealed neurochemically and morphologically to develop synapses leading to enhanced cognitive function. Dietary restriction as a nutritional intervention restored the altered metabolism of neuronal membranes with aging, providing a possible explanation for the longevity effect of dietary restriction. These results obtained with aging and dementia models of animals would benefit aged people.

  3. Catalpol ameliorates diabetic atherosclerosis in diabetic rabbits

    PubMed Central

    Liu, Jiang-Yue; Zheng, Chen-Zhao; Hao, Xin-Ping; Zhang, Dai-Juan; Mao, An-Wei; Yuan, Ping

    2016-01-01

    Catalpol, isolated from the roots of Rehmanniaglutinosa, Chinese foxglove, is an iridoid glycoside with antioxidant, anti-inflammatory and anti-hyperglycemic agent. The present study was to investigate the effects of catalpol on diabetic atherosclerosis in alloxan-induced diabetic rabbits. Diabetes was induced in rabbits by a hyperlipidemic diet and intravenous injection of alloxan (100 mg/kg). Rabbits were treated for 12 weeks. The fasting blood glucose, insulin, homeostasis model of insulin resistance, total cholesterol and triglyceride were measured. The thoracic aorta was excised for histology. The plasma and vascular changes including some markers of oxidative stress, inflammatory cytokines and fibrosis factors were examined. Plasma levels of fasting blood glucose, insulin and homeostasis model of insulin resistance were significantly decreased in catalpol group. Catalpol treatment ameliorated diabetic atherosclerosis in diabetic rabbits as demonstrated by significantly inhibited neointimal hyperplasia and macrophages recruitment. Catalpol treatment also enhanced the activities of superoxide dismutase, glutathione peroxidase, and increased the plasma levels of total antioxidant status, meanwhile reduced the levels of malondialdehyde, protein carbonyl groups and advanced glycation end product. Furthermore, catalpol also reduced circulating levels of tumor necrosis factor-α, monocyte chemotactic protein-1 and vascular cell adhesion molecule-1. Catalpol also decreased transforming growth factor-β1 and collagen IV mRNA and protein expressions in the vessels. Catalpol exerts an ameliorative effect on atherosclerotic lesion in alloxan-induced diabetic rabbits. The possible mechanisms may be related to inhibition of oxidative stress inflammatory response and anti-fibrosis and reduced aggregation of extracellular matrix. PMID:27830011

  4. 27 CFR 24.304 - Chaptalization (Brix adjustment) and amelioration record.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ameliorating material. If fruit juice other than grape is chaptalized and this juice or wine is ameliorated... Chaptalization (Brix adjustment) and amelioration record. (a) General. A proprietor who chaptalizes juice or ameliorates juice or wine, or both, shall maintain a record of the operation and the transaction date....

  5. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats.

    PubMed

    Yildiz, Gulserap; Yildiz, Yuksel; Ulutas, Pinar A; Yaylali, Asl; Ural, Muruvvet

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments.

  6. Evaluation of Soil Salinity Amelioration Technologies in Timpaki, Crete

    NASA Astrophysics Data System (ADS)

    Panagea, Ioanna; Daliakopoulos, Ioannis; Tsanis, Ioannis; Schwilch, Gudrun

    2015-04-01

    Salinization is a soil threat that adversely affects ecosystem services and diminishes soil functions in many arid and semi-arid regions. Soil salinity management depends on a range of factors, and can be complex expensive and time demanding. Besides taking no action, possible management strategies include amelioration and adaptation measures. The WOCAT Technologies Questionnaire is a standardized methodology for monitoring, evaluating and documenting sustainable land management practices through interaction with the stakeholders. Here we use WOCAT for the systematic analysis and evaluation of soil salinization amelioration measures, for the RECARE project Case Study in Greece, the Timpaki basin, a semi-arid region in south-central Crete where the main land use is horticulture in greenhouses irrigated by groundwater. Excessive groundwater abstractions have resulted in a drop of the groundwater level in the coastal part of the aquifer, thus leading to seawater intrusion and in turn to soil salinization due to irrigation with brackish water. Amelioration technologies that have already been applied in the case study by the stakeholders are examined and classified depending on the function they promote and/or improve. The documented technologies are evaluated for their impacts on ecosystem services, cost and input requirements. Preliminary results show that technologies which promote maintaining existing crop types while enhancing productivity and decreasing soil salinity such as composting, mulching, rain water harvesting and seed biopriming are preferred by the stakeholders. Further work will include result validation using qualitative approaches. Keywords: soil salinity; salinization; evaluation of soil salinization amelioration techniques; WOCAT; RECARE FP7 project; Timpaki Crete

  7. Biochar from commercially cultivated seaweed for soil amelioration.

    PubMed

    Roberts, David A; Paul, Nicholas A; Dworjanyn, Symon A; Bird, Michael I; de Nys, Rocky

    2015-04-09

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum--brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma--red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  8. Biochar from commercially cultivated seaweed for soil amelioration

    NASA Astrophysics Data System (ADS)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-04-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum - brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma - red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  9. Therapeutic miR-21 Silencing Ameliorates Diabetic Kidney Disease in Mice.

    PubMed

    Kölling, Malte; Kaucsar, Tamas; Schauerte, Celina; Hübner, Anika; Dettling, Angela; Park, Joon-Keun; Busch, Martin; Wulff, Xaver; Meier, Matthias; Scherf, Kristian; Bukosza, Nóra; Szénási, Gábor; Godó, Mária; Sharma, Amit; Heuser, Michael; Hamar, Peter; Bang, Claudia; Haller, Hermann; Thum, Thomas; Lorenzen, Johan M

    2017-01-04

    Diabetic nephropathy is the main cause of end-stage renal disease. MicroRNAs are powerful regulators of the genome, and global expression profiling revealed miR-21 to be among the most highly regulated microRNAs in kidneys of mice with diabetic nephropathy. In kidney biopsies of diabetic patients, miR-21 correlated with tubulointerstitial injury. In situ PCR analysis showed a specific enrichment of miR-21 in glomerular cells. We identified cell division cycle 25a (Cdc25a) and cyclin-dependent kinase 6 (Cdk6) as novel miR-21 targets in mesangial cells. miR-21-mediated repression of Cdc25a and Cdk6 resulted in impaired cell cycle progression and subsequent mesangial cell hypertrophy. miR-21 increased podocyte motility by regulating phosphatase and tensin homolog (Pten). miR-21 antagonism in vitro and in vivo in streptozotocin-induced diabetic mice decreased mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria, and fibrotic- and inflammatory gene expression. In conclusion, miR-21 antagonism rescued various functional and structural parameters in mice with diabetic nephropathy and, thus, might be a viable option in the treatment of patients with diabetic kidney disease.

  10. Rap1 Ameliorates Renal Tubular Injury in Diabetic Nephropathy

    PubMed Central

    Xiao, Li; Zhu, Xuejing; Yang, Shikun; Liu, Fuyou; Zhou, Zhiguang; Zhan, Ming; Xie, Ping; Zhang, Dongshan; Li, Jun; Song, Panai; Kanwar, Yashpal S.; Sun, Lin

    2014-01-01

    Rap1b ameliorates high glucose (HG)-induced mitochondrial dysfunction in tubular cells. However, its role and precise mechanism in diabetic nephropathy (DN) in vivo remain unclear. We hypothesize that Rap1 plays a protective role in tubular damage of DN by modulating primarily the mitochondria-derived oxidative stress. The role and precise mechanisms of Rap1b on mitochondrial dysfunction and of tubular cells in DN were examined in rats with streptozotocin (STZ)-induced diabetes that have Rap1b gene transfer using an ultrasound microbubble-mediated technique as well as in renal proximal epithelial tubular cell line (HK-2) exposed to HG ambiance. The results showed that Rap1b expression decreased significantly in tubules of renal biopsies from patients with DN. Overexpression of a constitutively active Rap1b G12V notably ameliorated renal tubular mitochondrial dysfunction, oxidative stress, and apoptosis in the kidneys of STZ-induced rats, which was accompanied with increased expression of transcription factor C/EBP-β and PGC-1α. Furthermore, Rap1b G12V also decreased phosphorylation of Drp-1, a key mitochondrial fission protein, while boosting the expression of genes related to mitochondrial biogenesis and antioxidants in HK-2 cells induced by HG. These effects were imitated by transfection with C/EBP-β or PGC-1α short interfering RNA. In addition, Rap1b could modulate C/EBP-β binding to the endogenous PGC-1α promoter and the interaction between PGC-1α and catalase or mitochondrial superoxide dismutase, indicating that Rap1b ameliorates tubular injury and slows the progression of DN by modulation of mitochondrial dysfunction via C/EBP-β–PGC-1α signaling. PMID:24353183

  11. Vitamin D ameliorates hepatic ischemic/reperfusion injury in rats.

    PubMed

    Seif, Ansam Aly; Abdelwahed, Doaa Mohamed

    2014-09-01

    Vitamin D, most commonly associated with the growth and remodeling of bone, has been shown to ameliorate ischemia/reperfusion injury (IRI) in some tissues, yet its underlying mechanism remains elusive. This study was designed to examine the protective effect of vitamin D, if any, against hepatic IRI in rats and the underlying mechanism involved. Adult female Wistar rats were randomly divided into control, sham-operated (sham), ischemia/reperfusion (I/R), and ischemic-reperfused vitamin D-treated (vit D) groups. Rats in the I/R and vit D groups were subjected to partial (70%) hepatic ischemia for 45 min, followed by 1 h of reperfusion. Vitamin D was given to rats orally in a dose of 500 IU/kg daily for 2 weeks before being subjected to I/R. Markers of liver damage, oxidative stress, inflammation and apoptosis were evaluated. Hepatic morphology was also examined. Vit D-treated rats had significantly lower serum levels of alanine aminotransferase, aspartate aminotransferase, and γ glutamyl transferase compared to rats in the I/R group. Also, vit D-treated rats showed a significant decrease in malondialdehyde, interleukin-1 beta, interleukin-6, tumor necrosis factor-α, nuclear factor κB, B cell leukemia/lymphoma 2-associated X protein, cytochrome c, and caspase-3 levels, with higher levels of glutathione peroxidase and B cell lymphoma 2 protein levels in liver tissues compared to I/R rats. Histological examination showed less damaged liver tissues with amelioration of apoptotic signs in the vit D group compared to the I/R group. In conclusion, vitamin D supplementation ameliorates hepatic IRI mostly by alleviating the inflammatory-apoptotic response mediated by the oxidative reperfusion injury insult.

  12. Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals.

    PubMed

    Morris, Laurel S; Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J; Orban, Csaba; Passetti, Filippo; Paterson, Louise M; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor M; Bullmore, Edward T; Lingford-Hughes, Anne R; Deakin, Bill; Nutt, David J; Sahakian, Barbara J; Robbins, Trevor W; Voon, Valerie

    2017-02-28

    Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.

  13. Gemigliptin ameliorates Western-diet-induced metabolic syndrome in mice.

    PubMed

    Choi, Seung Hee; Leem, Jaechan; Park, Sungmi; Lee, Chong-Kee; Park, Keun-Gyu; Lee, In-Kyu

    2017-02-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks. Gemigliptin treatment attenuated WD-induced body mass gain, hypercholesterolemia, adipocyte hypertrophy, and macrophage infiltration into adipose tissue, which were accompanied by an increased expression of uncoupling protein 1 in subcutaneous fat. These events contributed to improved insulin sensitivity, as assessed by the homeostasis model assessment of insulin resistance and intraperitoneal insulin tolerance test. Furthermore, gemigliptin reduced WD-induced hepatic triglyceride accumulation via inhibition of de novo lipogenesis and activation of fatty acid oxidation, which was accompanied by AMP-dependent protein kinase activation. Gemigliptin ameliorated WD-induced hepatic inflammation and fibrosis through suppression of oxidative stress. These results suggest that DPP-4 inhibitors may represent promising therapeutic agents for metabolic syndrome beyond their current role as antihyperglycemic agents.

  14. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    PubMed Central

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  15. Antihyperlipidemic Effect of a Polyherbal Mixture in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Shafiee-Nick, Reza; Rakhshandeh, Hassan; Borji, Abasalt

    2013-01-01

    The effects of a polyherbal mixture containing Allium sativum, Cinnamomum zeylanicum, Citrullus colocynthis, Juglans regia, Nigella sativa, Olea europaea, Punica granatum, Salvia officinalis, Teucrium polium, Trigonella foenum, Urtica dioica, and Vaccinium arctostaphylos were tested on biochemical parameters in diabetic rats. The animals were randomized into three groups: (1) normal control, (2) diabetic control, and (3) diabetic rats which received diet containing 15% (w/w) of this mixture for 4 weeks. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg). At the end of experiment, the mixture had no significant effect on serum hepatic enzymes, aspartate aminotransferase, and alanine aminotransferase activities. However, the level of fasting blood glucose, water intake, and urine output in treated group was lower than that in diabetic control rats (P < 0.01). Also, the levels of triglyceride and total cholesterol in polyherbal mixture treated rats were significantly lower than those in diabetic control group (P < 0.05). Our results demonstrated that this polyherbal mixture has beneficial effects on blood glucose and lipid profile and it has the potential to be used as a dietary supplement for the management of diabetes. PMID:24383002

  16. Effect of Resveratrol on Behavioral Performance of Streptozotocin-induced Diabetic Mice inAnxiety Tests

    PubMed Central

    Damián, Juan P.; Acosta, Victoria; Da Cuña, Maira; Ramírez, Isara; Oddone, Natalia; Zambrana, Ana; Bervejillo, Verónica; Benech, Juan C.

    2014-01-01

    The aim of this study was to evaluate with anxiety tests the effect of resveratrol (RSV) on streptozotocin (STZ)-induced diabetic mouse behavioral performance at the second and fourth week of treatment. Confirmed diabetic mice (>250 mg/dl of glucose in blood after STZ injection) were treated with RSV (RDM, n=12) or control treated (DM, n=12) for 4 weeks. DM and RDM were tested in the Open Field Test (OFT) and Elevated Plus Maze (EPM). In the second week of RSV treatment, a higher grooming frequency (P<0.05) and a lower defecation and rearing frequency (P<0.05) were detected in the OFT in the RDM group compared with the DM. There was a higher grooming frequency (P<0.05) and higher percentage of entries in open arms (P<0.05) in the RDM group than in the DM group in the EPM. However, in the fourth week of RSV treatment, the only effect observed was a higher grooming frequency in the RDM group than in the DM group (P<0.05) in the EPM. In conclusion, RSV treatment in diabetic mice provoked anxiolytic-like effects in both tests (OFT and EPM), and these effects were observed in a short time window (2 weeks). It is suggested that RSV may help diabetic animals to adapt to new stressing and anxiety situations and thus to improve their welfare. PMID:25077757

  17. Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis.

    PubMed

    Kutlu, O; Karaguzel, E; Gurgen, S G; Okatan, A E; Kutlu, S; Bayraktar, C; Kazaz, I O; Eren, H

    2016-05-01

    We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions.

  18. Increased intrinsic mitochondrial respiratory capacity in skeletal muscle from rats with streptozotocin-induced hyperglycemia

    PubMed Central

    Larsen, Steen; Scheede-Bergdahl, Celena; Whitesell, Thomas; Boushel, Robert; Bergdahl, Andreas

    2015-01-01

    Type I diabetes mellitus (T1DM) is a chronic disorder, characterized by an almost or complete insulin deficiency. Widespread tissue dysfunction and deleterious diabetes-complications are associated with long-term elevations of blood glucose. The aim of this study was to investigate the effects of type I diabetes, as induced by streptozotocin, on the mitochondria in skeletal muscles that predominantly consist of either slow or fast twitch fibers. Soleus (primarily slow twitch fiber type) and the plantaris muscle (mainly fast twitch fiber type) were removed in order to measure mitochondrial protein expression and integrated mitochondrial respiratory function. Mitochondrial capacity for oxidative phosphorylation (OXPHOS) was found to be higher in the slow (more oxidative) soleus muscle from STZ rats when evaluating lipid and complex I linked OXPHOS capacity, whereas no difference was detected between the groups when evaluating the more physiological complex I and II linked OXPHOS capacity. These findings indicate that chronic hyperglycemia results in an elevated intrinsic mitochondrial respiratory capacity in both soleus and, at varying degree, plantaris muscle, findings that are consistent with human T1DM patients. PMID:26197936

  19. Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Akkoç, Tolga; Eraslan, Muhsin; Şahin, Özlem; Özkara, Selvinaz; Vardar Aker, Fugen; Subaşı, Cansu; Karaöz, Erdal; Akkoç, Tunç

    2016-01-01

    Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function. PMID:27300133

  20. Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.

    PubMed

    El-Akabawy, Gehan; El-Kholy, Wael

    2014-05-01

    Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain.

  1. Antihyperglycemic activity of Piper betle leaf on streptozotocin-induced diabetic rats.

    PubMed

    Santhakumari, P; Prakasam, A; Pugalendi, K V

    2006-01-01

    Piper betle, an indigenous medicinal plant, has a folk (Siddha and Ayurvedha) reputation in the rural southern India. The present study was carried out to evaluate the effect of P. betle on glucose metabolism since it is consumed as betel-quid after meals. Plasma levels of glucose and glycosylated hemoglobin and activities of liver hexokinase and gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase in control and streptozotocin (STZ) diabetic rats were assayed. Oral administration of leaf suspension of P. betle (75 and 150 mg/kg of body weight) for 30 days resulted in significant reduction in blood glucose (from 205.00 +/- 10.80 mg/dL to 151.30 +/- 6.53 mg/dL) and glycosylated hemoglobin and decreased activities of liver glucose-6-phosphatase and fructose-1,6-bisphosphatase, while liver hexokinase increased (P < .05), in STZ diabetic rats when compared with untreated diabetic rats. P. betle at a dose of 75 mg/kg of body weight exhibited better sugar reduction than 150 mg/kg of body weight. In addition, protection against body weight loss of diabetic animals was also observed. The effects produced by P. betle were compared with the standard drug glibenclamide. Thus, the present study clearly shows that P. betle intake influences glucose metabolism beneficially.

  2. Antidiabetic activity of benzopyrone analogues in nicotinamide-streptozotocin induced type 2 diabetes in rats.

    PubMed

    Nayak, Yogendra; Hillemane, Venkatachalam; Daroji, Vijay Kumar; Jayashree, B S; Unnikrishnan, M K

    2014-01-01

    Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D) was induced in Wistar rats by streptozotocin (60 mg/kg, i.p.) followed by nicotinamide (120 mg/kg i.p.). Rats having fasting blood glucose (FBG)>200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR) was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.

  3. Hypolipidaemic activity of Helicteres isora L. bark extracts in streptozotocin induced diabetic rats.

    PubMed

    Kumar, G; Murugesan, A G

    2008-02-28

    In this study, the hypolipidaemic effect of an aqueous extract of the bark of Helicteres isora was investigated in streptozotocin (STZ)-induced diabetic rats. Administration of the bark extract of Helicteres isora (100 and 200 mg/kgb.w.) for 21 days resulted in significant reduction in serum and tissue cholesterol, phospholipids, free fatty acids and triglycerides in STZ diabetic rats. In addition to that, significant (p<0.05) decrease in high-density lipoprotein (HDL) whereas significant increase (p<0.05) low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) were observed in STZ diabetic rats, which were normalized after 21 days of bark extract treatment. The bark extract at a dose of 200 mg/kgb.w. showed much significant hypolipidaemic effect than at the dose of 100 mg/kgb.w.

  4. Fermented soy permeate reduces cytokine level and oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Malardé, Ludivine; Groussard, Carole; Lefeuvre-Orfila, Luz; Vincent, Sophie; Efstathiou, Théo; Gratas-Delamarche, Arlette

    2015-01-01

    Oxidative stress and inflammation are involved in the development of type 1 diabetes and its complications. Because two compounds found in soy, that is, isoflavones and alpha-galactooligosaccharides, have been shown to exert antioxidant and anti-inflammatory effects, this study aimed to assess the effects of a dietary supplement containing these two active compounds, the fermented soy permeate (FSP). We hypothesized that FSP would be able to reduce in vivo oxidative stress and inflammation in streptozotocin (STZ)-induced type 1 diabetic rats. Thirty male Wistar rats were divided into the control placebo, diabetic placebo, and diabetic FSP-supplemented groups. They received daily, by oral gavage, water (placebo groups) or diluted FSP (0.1 g/day; FSP-supplemented group). After 3 weeks, glycemic regulation (glycemia and fructosamine level); the plasma level of carboxymethyllysine (CML), a marker of systemic oxidative stress in diabetes; and the plasma levels of inflammatory markers (CRP, IL-1β, IL-6, and uric acid) were evaluated. Markers of oxidative damage (isoprostanes and GSH/GSSG), antioxidant enzymatic activity (SOD and GPX), and Mn-SOD content were determined in skeletal muscle (gastrocnemius). Diabetic placebo rats exhibited higher CML levels, lower SOD and GPX activities, and decreased Mn-SOD contents. FSP supplementation in diabetic animals normalized the CML and antioxidant enzymatic activity levels and tended to increase Mn-SOD expression. The markers of inflammation whose levels were increased in the diabetic placebo group were markedly decreased by FSP (IL-1β: -75%, IL-6: -46%, and uric acid: -17%), except for CRP. Our results demonstrate that FSP exhibited antioxidant and anti-inflammatory properties in vivo in STZ-induced diabetic rats.

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

    PubMed Central

    Minaz, Nathani; Razdan, Rema

    2016-01-01

    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. PMID:27721541

  6. Efficacy of Annona squamosa on wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Ponrasu, Thangavel; Suguna, Lonchin

    2012-12-01

    Annona squamosa L. (Annonaceae), commonly known as custard apple, mainly used for its edible fruit, is also recognised with numerous medicinal properties. As there is no report on the efficacy of this plant for wound healing, we examined the efficacy of ethanolic extract of A. squamosa leaves on wound repair in streptozotocin-nicotinamide-induced diabetic rats. Open excision wounds were made on the back of rats. The drug at a dosage of 100 mg/kg body wt was reconstituted in 200 µl of phosphate buffered saline and applied topically once daily for the treated wounds. The control wounds were left untreated. Wound tissues formed on days 4, 8, 12 and 16 (post-wound) were used to estimate DNA, total protein, total collagen, hexosamine and uronic acid. Levels of lipid peroxides were also evaluated along with tensile strength and period of epithelialisation. A. squamosa L. increased cellular proliferation and collagen synthesis at the wound site as evidenced by increase in DNA, protein and total collagen. The treated wounds were observed to heal much faster as proved by enhanced rates of epithelialisation and wound contraction, which was also confirmed by histopathological examinations. The results strongly substantiate the beneficial effects of the topical application of A. squamosa L. in the acceleration of normal and diabetic wound healing.

  7. Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ghasemi, Mohsen; Zendehbad, Bamdad; Zabihi, Hoda; Hosseini, Mahmoud; Hadjzadeh, Mousa Al Reza; Hayatdavoudi, Parichehr

    2016-01-01

    Background: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. Aims: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. Study Design: Animal experimentation. Methods: The rats were divided into three groups: 1-control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. Results: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. Conclusion: Leptin can exert positive effects on memory impairments in diabetic rats. PMID:26966625

  8. Berberine nanosuspension enhances hypoglycemic efficacy on streptozotocin induced diabetic C57BL/6 mice.

    PubMed

    Wang, Zhiping; Wu, Junbiao; Zhou, Qun; Wang, Yifei; Chen, Tongsheng

    2015-01-01

    Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.

  9. Response of thymus lymphocytes to streptozotocin-induced diabetes and exogenous vitamin C administration in rats.

    PubMed

    Ozerkan, Dilşad; Ozsoy, Nesrin; Cebesoy, Suna

    2014-12-01

    Diabetes causes oxidative stress, which in turn generates excessive free radicals resulting in cellular damage. Vitamin C is an antioxidant that protects tissues and organs from oxidative stress. The thymus is one of the most important lymphoid organs, which regulates T-lymphocyte proliferation and maturation. The aim of this study is to investigate the protective effects of vitamin C on the thymus of streptozotocin (STZ)-induced diabetic rats. The mitotic activity and cell integrity of thymic lymphocytes were explored. Wistar Albino rats were divided into three groups: control (Group 1), STZ-diabetes (Group 2) and vitamin C-treated STZ-diabetics (Group 3). Rats received a single intraperitoneal injection of 45 mg/kg STZ to induce diabetes. Vitamin C (20 mg/kg) was administered intragastrically. Semithin and ultrathin sections were examined under a light or an electron microscope, respectively. Considerable numbers of mitotic lymphocytes were observed in the thymus of control rats. In the diabetic rats, however, numbers of mitotic lymphocytes decreased to ∼57% of controls, and cell division abnormalities were observed. Additionally, diabetic rats showed degeneration in the structure of the thymus including trabecular thickening, accumulation of lipid vacuoles, heterochromatic nuclei and loss of mitochondrial cristae. Degradation of medullar and cortical integrity was also detected. In the vitamin C-treated STZ-diabetic group, the structure of the thymus and mitotic activity of the lymphocytes were similar to the control group. These results suggest that vitamin C protects the thymus against injury caused by diabetes and restores thymocyte mitotic activity.

  10. Favorable effects of vildagliptin on metabolic and cognitive dysfunctions in streptozotocin-induced diabetic rats.

    PubMed

    El Batsh, Maha M; El Batch, Manal M; Shafik, Noha M; Younos, Ibrahim H

    2015-12-15

    Progression of diabetes mellitus is accompanied by metabolic disorders together with psychological deficits including cognitive dysfunctions. Herein, we used a murine streptozotocin (STZ)-induced diabetes to investigate the beneficial effects of vildagliptin not only on metabolic abnormalities, but also on diabetes-induced cognitive decline. Sixty rats were divided randomly and equally into 2 groups; one remains normal and the other serves as STZ- induced diabetic. Both groups were further divided equally into 2 groups; one received vehicle and the other received oral vildagliptin for 8 weeks. Cognitive behavior was assessed using novel object recognition test. Blood samples were collected to measure metabolic parameters and dipeptidyl peptidase (DPP)-IV activity. Brains were removed and investigated for the levels of inflammatory and oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α), in addition to brain-derived neurotrophic factor (BDNF) and relative expression of nuclear factor kappa B (NF-κB)/p65. Treatment of STZ-induced diabetic rats with vildagliptin increased their body weight and corrected diabetes-induced memory and learning impairment. Moreover, vildagliptin significantly decreased serum levels of glucose and lipids (except high density lipoprotein) together with brain MDA, TNF-α, serum DPP-IV activities and NF-κB/p65 gene expression. On the other hand, vildagliptin significantly increased brain BDNF, SOD as well as serum insulin. Results suggested that vildagliptin has a protective role in counteracting both metabolic abnormalities and memory deficits in diabetic rats, possibly via its anti-hyperglycemic, anti-inflammatory, antioxidant effects, together with reduction of brain NF-κB/p65 over expression.

  11. Effect of Cordyceps sinensis and taurine either alone or in combination on streptozotocin induced diabetes.

    PubMed

    El Zahraa Z El Ashry, Fatma; Mahmoud, Mona F; El Maraghy, Nabila N; Ahmed, Ahmed F

    2012-03-01

    The present study aimed to investigate the antidiabetic effects of Cordyceps sinensis, taurine and their combination in comparison with glibenclamide both in vivo and in vitro using streptozotocin rat model. The diabetic rats were orally given glibenclamide, C. sinensis, taurine or Cordyceps and taurine combination for 21 days. Their effects were studied both in vivo and in vitro. Oral administration of Cordyceps, taurine and their combination decreased serum glucose, fructosamine, total cholesterol, triglycerides levels, insulin resistance index and pancreatic malondialdehyde content. Cordyceps significantly increased serum insulin, HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content. However, taurine was unable to elevate pancreatic GSH level to a significant level. These natural products and their combinations were more effective than glibenclamide in reducing insulin resistance index and they had stronger antioxidant properties. Cordyceps and taurine significantly enhanced glucose uptake by diaphragms of normal and diabetic rats in absence and presence of insulin. In conclusion, Cordyceps and taurine either alone or in combination have less potent hypoglycemic effects than glibenclamide; however, they have more ability to reduce insulin resistance and stronger antioxidant properties.

  12. Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Aseer, Kanikkai Raja; Kim, Sang Woo; Choi, Myung-Sook; Yun, Jong Won

    2015-01-01

    Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels.

  13. SEXUAL BEHAVIOUR, SPERM QUANTITY AND QUALITY AFTER SHORT-TERM STREPTOZOTOCIN-INDUCED HYPERGLYCAEMIA IN RATS.

    EPA Science Inventory

    Studies of diabetes mellitus in the streptozotocin rat model suggest that sexual dysfunctions may result from diabetes-induced alterations of the neuroendocrine-reproductive tract axis. Our investigation was performed to better define the effects of short-term hyperglycemia on ra...

  14. Antihyperglycemic Effect of Ganoderma Lucidum Polysaccharides on Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Li, Fenglin; Zhang, Yiming; Zhong, Zhijian

    2011-01-01

    The current study evaluated the glucose-lowering effect of ganoderma lucidum polysaccharides (Gl-PS) in streptozotocin (STZ)-induced diabetic mice. The diabetic mice were randomly divided into four groups (8 mice per group): diabetic control group, low-dose Gl-PS treated group (50 mg/kg, Gl-PS), high-dose Gl-PS treated group (150 mg/kg, Gl-PS) and positive drug control treated group (glibenclamide, 4 mg/kg), with normal mice used as the control group. Body weights, fasting blood glucose (FBG), serum insulin and blood lipid levels of mice were measured. After 28 days of treatment with Gl-PS, body weights and serum insulin levels of the Gl-PS treated groups was significantly higher than that of the diabetic control group, whereas FBG levels was significantly lower. Moreover, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels of the Gl-PS treated groups had dropped, whereas the high density lipoprotein cholesterol (HDL-C) levels had increased. In addition, according to acute toxicity studies, Gl-PS did not cause behavioral changes and any death of mice. These data suggest that Gl-PS has an antihyperglycemic effect. Furthermore, considering the Gl-PS effects on lipid profile, it may be a potential hypolipidaemic agent, which will be a great advantage in treating diabetic conditions associated with atherosclerosis or hyperlipidemia. PMID:22016649

  15. Hypertension influences the exponential progression of inflammation and oxidative stress in streptozotocin-induced diabetic kidney

    PubMed Central

    Muthaian, Rupadevi; Pakirisamy, Rajaa Muthu; Parasuraman, Subramani; Raveendran, Ramasamy

    2016-01-01

    Objective: To investigate the association of hypertension coexisting with diabetes mellitus with oxidative stress and inflammation in the kidneys of streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Male Wistar rats were used for the experiments. Blood glucose (BG), urea, blood pressure (BP), and heart rate (HR) were analyzed before and 48 h after STZ injection. Further, these parameters were monitored up to 3 months of diabetes induction. Subsequently, the inflammatory markers (C-reactive protein, tumor necrosis factor-alpha, and nitrate) and oxidative stress markers were estimated after 3 months of diabetes induction in the kidney homogenate. Histological analysis of renal tissue was also carried out. Results: Linear elevation of BG, urea, mean arterial pressure (MAP), and HR was observed up to 3 months of diabetes induction. In the same manner, inflammatory and oxidative stress markers were also found to be significantly increased. Notably, the histological analysis revealed the signs of nephropathy such as increased mesangial cell number, thickness of basement membrane, and renal artery. Inflammatory and oxidative stress markers positively correlated with elevated BP and BG, but the correlation was better with BP rather than BG. Conclusion: Hypertension has a strong implication in the increased oxidative stress and inflammation of diabetic kidney at the very early stage of diabetes mellitus. PMID:28163536

  16. The effects of dexpanthenol in streptozotocin-induced diabetic rats: histological, histochemical and immunological evidences.

    PubMed

    Gulle, K; Ceri, N G; Akpolat, M; Arasli, M; Demirci, B

    2014-10-01

    This study was designed to investigate the effects of Dexpanthenol (Dxp) on liver and pancreas histology and cytokine levels in streptozotocine (STZ)-induced diabetic rats. Twenty-four Wistar albino male rats were divided into four groups: control, Dxp, STZ-induced diabetic (STZ) and diabetic treatment with Dexpanthenol (STZ-Dxp) groups. Experimental diabetes was induced by single dose STZ (50 mg/kg) intraperitoneally (i.p.). After administration of STZ, the STZ-Dxp group began to receive a 300 mg/kg/day i.p. dose of Dxp for 6 weeks. Liver and pancreas tissues of the control group were in normal morphology. Liver tissue of STZ group showed vacuolisation of hepatocytes in the liver parenchyma with enlargement of sinusoidal spaces and increasing amounts of connective tissue in the portal area. Pancreatic section of STZ group displayed β-cells with of cytoplasmic mass, reduction of islet size, and atrophy. The STZ-Dxp group that received Dxp treatment exhibit partially normal hepatic parenchyma. Histochemical examinations revealed that the diabetes-induced glycogen depletion markedly improved with the Dxp treatment (p⟨0.001). The severity of degenerative alteration was lessened by Dxp supplementation in the STZ-Dxp group. Induction of STZ presented a significant increase both in interleukin-1α (IL-1α) (p=0.033) and monocyte chemotactic protein-1 (MCP-1) (p=0.011) levels, when compared with the control rats. DXP-treated diabetic rats' IL-1α and MCP-1 levels were similar to control value. This evidence suggests that Dxp is effective in reducing STZ-induced, diabetic-related complications and may be beneficial for the treatment of diabetic patients.

  17. Enhanced alpha-kinase 1 accelerates multiple early nephropathies in streptozotocin-induced hyperglycemic mice.

    PubMed

    Kuo, Tzer-Min; Hsu, Hui-Ting; Chung, Chia-Min; Yeh, Kun-Tu; Wu, Cheng-Tien; Lee, Chi-Pin; Chiang, Shang-Lun; Huang, Chung-Ming; Ko, Ying-Chin

    2016-11-01

    Alpha-kinase 1 (ALPK1) is associated with chronic kidney disease (CKD), type 2 diabetes mellitus and gout. Elevated ALPK1 levels have been observed in the kidneys of patients with diabetes and the white blood cells of patients with gout. As renal injury is a common outcome of CKD, diabetes and gout, the aim of this study was to investigate the effect of ALPK1 in the development of renal injury in a hyperglycemic condition. Hyperglycemia was induced in wild-type and ALPK1 transgenic mice by an intraperitoneal injection of streptozotocin (STZ). Functional and histological examinations were performed after 3weeks. STZ-treated ALPK1 transgenic mice exclusively showed arteriolar sclerosis and fibrous thickening of the Bowman's capsule in the kidney. This was accompanied by body weight loss, severe hyperglycemia, and low serum insulin levels. Renal renin and serum renin protein levels were higher in STZ-treated ALPK1 transgenic mice, whereas cGKII protein level was decreased by ALPK1 in human embryonic kidney 293 (HEK293) cells. ALPK1 up-regulated TGF-beta1 levels and transcription of fibrosis-related genes, including MMP-9, FIBRONECTIN, and TIMP1. MSU crystals increased ALPK1 transcription in cultured kidney cells. Finally, ALPK1 enhanced production of MSU crystals-induced IL-1beta in mice. Stimulation of soluble sodium urate induced IL-1beta and Alpk1 mRNA production in mice kidney. Taken together, these data show that an increase in ALPK1 results in accelerated fibrotic nephropathies, primarily through the enhancement of renin, TGF-beta1, and IL-1beta. Renal or blood ALPK1 levels are involved in the induction of fibrotic renal injury in an experimental model of hyperglycemia.

  18. Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats.

    PubMed

    Jang, Y Y; Song, J H; Shin, Y K; Han, E S; Lee, C S

    2000-10-01

    Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. Several antioxidants have been described as beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1, 10-dimethoxyaporphine) is a major alkaloid found in the leaves and bark of boldo (Peumus boldus Molina), and has been shown to possess antioxidant activity and anti-inflammatory effects. From this point of view, the possible anti-diabetic effect of boldine and its mechanism were evaluated. The experiments were performed on male rats divided into four groups: control, boldine (100 mg kg(-1), daily in drinking water), diabetic [single dose of 80 mg kg(-1)of streptozotocin (STZ), i.p.] and diabetic simultaneously fed with boldine for 8 weeks. Diabetic status was evaluated periodically with changes of plasma glucose levels and body weight in rats. The effect of boldine on the STZ-induced diabetic rats was examined with the formation of malondialdehydes and carbonyls and the activities of endogenous antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in mitochondria of the pancreas, kidney and liver. The scavenging action of boldine on oxygen free radicals and the effect on mitochondrial free-radical production were also investigated. The treatment of boldine attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. The levels of malondialdehyde (MDA) and carbonyls in liver, kidney and pancreas mitochondria were significantly increased in STZ-treated rats and decreased after boldine administration. The activities of mitochondrial manganese superoxide dismutase (MnSOD) in the liver, pancreas and kidney were significantly elevated in STZ-treated rats. Boldine administration decreased STZ-induced elevation of MnSOD activity in kidney and pancreas mitochondria, but not in liver mitochondria. In the STZ-treated group, glutathione peroxidase activities decreased in liver mitochondria, and were elevated in pancreas and kidney mitochondria. The boldine treatment restored the altered enzyme activities in the liver and pancreas, but not the kidney. Boldine attenuated both STZ- and iron plus ascorbate-induced MDA and carbonyl formation and thiol oxidation in the pancreas homogenates. Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner. The alkaloid significantly attenuated the production of superoxide anions, hydrogen peroxide and nitric oxide caused by liver mitochondria. The results indicate that boldine may exert an inhibitory effect on STZ-induced oxidative tissue damage and altered antioxidant enzyme activity by the decomposition of reactive oxygen species and inhibition of nitric oxide production and by the reduction of the peroxidation-induced product formation. Boldine may attenuate the development of STZ-induced diabetes in rats and interfere with the role of oxidative stress, one of the pathogeneses of diabetes mellitus.

  19. Decreased level of albumin in peripheral blood mononuclear cells of streptozotocin-induced diabetic rats.

    PubMed

    Park, Ki Tae; Yun, Chul-Ho; Bae, Chun-Sik; Ahn, Taeho

    2014-08-01

    We investigated the phenotypic level of albumin in peripheral blood mononuclear cells (PBMC) of streptozotocin (STZ)-induced diabetic rats. A specific reduction of albumin was identified by 2-dimensional electrophoresis and mass spectrometry. Decreased albumin content was also confirmed by immunoblotting and quantitative real-time PCR. Since albumin is a major and predominant antioxidant in plasma, the PBMC albumin may also contribute to their antioxidant activity. By measuring the amount of H2O2, lipid peroxidation and the redox form of glutathione, it was found that the production of the oxidative stress was elevated in STZ-diabetic rats compared to that of normal control. We suggest, therefore, that decreased albumin content may lead to the decreased antioxidant activity in the PBMC of type 1 diabetic rats.

  20. P2X7 receptor knockout prevents streptozotocin-induced type 1 diabetes in mice.

    PubMed

    Vieira, Flávia Sarmento; Nanini, Hayandra Ferreira; Takiya, Christina Maeda; Coutinho-Silva, Robson

    2016-01-05

    Type 1 diabetes (T1D) is caused by autoimmune destruction of islet of Langerhans β-cells. P2X7 receptors (P2X7R) modulate proinflammatory immune responses by binding extracellular ATP, a classic 'danger signal'. Here, we evaluated whether the P2X7R has a role in T1D development. P2X7(-/-) mice are resistant to TD1 induction by streptozotocin (STZ) treatment, with no increase in blood glucose, decrease in insulin-positive cells, and pancreatic islet reduction, compared to WT (C57BL/6) mice. Also, the levels of proinflammatory mediators (IL-1β, IFN-γ and NO) did not increase after STZ treatment in P2X7(-/-) animals, with reduced infiltration of CD4(+), CD8(+), B220(+), CD11b(+) and CD11c(+) cells in the pancreatic lymph nodes. Treatment with a P2X7 antagonist mimicked the effect of P2X7 knockout, preventing STZ-induced diabetes. Our results show that the absence of the P2X7R provides resistance in the induction of diabetes in this model, and suggest that therapy targeting the P2X7R may be useful against clinical T1D.

  1. Hypoglycemic activity of Ailanthus excelsa leaves in normal and streptozotocin-induced diabetic rats.

    PubMed

    Cabrera, W; Genta, S; Said, A; Farag, A; Rashed, K; Sánchez, S

    2008-03-01

    The hypoglycemic activity of a 70% methanol extract from the leaves of Ailanthus excelsa Roxb. (Simaroubaceae) was studied in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Oral administration of the extract at doses of 14, 70 and 350 mg/kg body weight caused no significant changes in fasting blood glucose levels of normal rats. In an oral glucose tolerance test, the extract produced a significant decrease in glycemia 90 min after the glucose pulse. Daily administration of A. excelsa extract for 60 days produced a significant hypoglycemic effect in diabetic animals. In addition, this treatment improved the altered renal function observed in diabetic control rats. This study suggests that Ailanthus leaf extract could be potentially useful for post-prandial hyperglycemia treatment.

  2. Elevated expression of liver X receptor alpha (LXRα) in myocardium of streptozotocin-induced diabetic rats.

    PubMed

    Cheng, Yongxia; Liu, Guibo; Pan, Qian; Guo, Sufen; Yang, Xianghong

    2011-12-01

    The present study was designed to investigate the myocardial expression of liver X receptor alpha (LXRα) in a streptozotocin (STZ)-induced diabetic rat model. Immunohistochemical staining, quantitative real-time RT-PCR, and Western blot analysis were used to determine the expression of LXRα in the myocardium of STZ-induced diabetic rats. The myocardial expression of LXRα target genes, long-chain acyl-CoA synthetase 3 (ACSL3), fatty acid transporter protein (FAT/CD36), ATP-binding cassette transporter A1 (ABCA1), and ABCG1 were also detected. Bisulfite sequencing analysis was employed to examine the methylation status of the CpG island at the LXRα promoter region in the myocardium of STZ-induced diabetic rats. We found that LXRα mRNA and protein expression in the left ventricles, right ventricles, and atria of diabetic rats were gradually increased during the progression of diabetic cardiomyopathy (DCM). The mRNA expression levels of ACSL3 and FAT/CD36 and the protein expression levels of ABCA1 and ABCG1 were also markedly increased in different heart chambers of diabetic rats. Moreover, there was a significant difference in the methylation status of LXRα gene between the ventricles of control and diabetic rats (P < 0.05). Our findings suggest that elevated expression of LXRα may be involved in the progression of DCM, and demethylation of LXRα is likely to be responsible for its increased expression in myocardial tissues.

  3. An experimental assessment of toxic potential of nanoparticle preparation of heavy metals in streptozotocin induced diabetes.

    PubMed

    Gandhi, Sonia; Srinivasan, B P; Akarte, Atul Sureshrao

    2013-11-01

    Nanoparticle preparations of heavy metals have attracted enormous scientific and technological interest. Biologically produced nanoparticle preparations of heavy metals are elaborately described in traditional texts and being widely prescribed. The underlying interactions of nano preparations within the physiological fluids are key feature to understand their biological impact. In this perspective, we performed an experimental assessment of the toxicity potential of a marketed metallic preparation named Vasant Kusumakar Ras (VKR), wherein different heavy metals in composite form are reduced to nanoparticle size to produce the desired effect in diabetes and its complications. VKR (50mg/kg) was administered to Albino Wistar rats rendered diabetic using streptozotocin (90mg/kg) in 2 days old neonates. Anti-hyperglycemic effect was observed with VKR along with increased levels of plasma insulin. Renal variables including total proteins and albumin along with glomerular filtration rate were found to improve biochemically. The results were supplemented by effects on different inflammatory and growth factors like TNF-α, nitric oxide, TGF-β and VEGF. However, the results observed in kidney histopathology were not in accordance with the biochemical parameters. Inflammation observed in kidney was confirmed by immunostaining metallothionein, which was due to the accumulation of heavy metals. Furthermore, mercury accumulation in kidney further confirmed by autometallography, which activated mononuclear phagocyte system, which generated an immune response. This was further supported by increase in the extent of apoptosis in kidney tissues. In conclusion, nanoparticle preparations of heavy metals can be toxic to kidney if it is not regulated with respect to its surface chemistry and dosage.

  4. Antihyperglycemic effect of thymoquinone and oleuropein, on streptozotocin-induced diabetes mellitus in experimental animals

    PubMed Central

    Sangi, Sibghatullah Muhammad Ali; Sulaiman, Mansour Ibrahim; El-wahab, Mohammed Fawzy Abd; Ahmedani, Elsamoual Ibrahim; Ali, Soad Shaker

    2015-01-01

    Background: Diabetes mellitus is one of the most important diseases related with endocrines. Its main manifestation includes abnormal metabolism of carbohydrates and lipids and inappropriate hyperglycemia that is caused by absolute or relative insulin deficiency. It affects humankind worldwide. Objectives: Our research was aimed to observe antihyperglycemic activity of thymoquinone and oleuropein. Materials and Methods: In this study, rats were divided into six groups, 6 rats in each. Diabetes was inducted by streptozotocin (STZ). The level of fasting blood glucose was determined for each rats during the experiment, doses of thymoquinone and oleuropein (3 mg/kg and 5 mg/kg) for both, were injected intraperitoneal. Pancreatic tissues were investigated to compare β-cells in diabetic and treated rats. Result and Conclusion: It was found that thymoquinone and oleuropein significantly decrease serum Glucose levels in STZ induced diabetic rats. PMID:26664013

  5. Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats

    PubMed Central

    POMJUNYA, Atchariya; RATTHANOPHART, Jasada; FUNGFUANG, Wirasak

    2017-01-01

    The present study investigated the effects of Vernonia cinerea (VC) on the reproductive function in streptozotocin (STZ)-induced diabetic male rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: group 1, normal control rats; group 2, diabetic untreated rats; group 3, diabetic rats treated with VC (10 mg/kg); and group 4, diabetic rats treated with VC (40 mg/kg). Diabetes mellitus (DM) was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 30 consecutive days. Body weight, blood glucose, food intake, epididymal sperm parameters, testicular microstructure and serum testosterone levels were evaluated. VC treatment significantly restored the sperm motility and testosterone concentration, and decreased the testicular histopathological changes in DM rats. Moreover, high-dose VC exhibited an antidibetic activity and significantly improved the sperm count. In conclusion, we found, for the first time, that administration of VC significantly restored the testicular function and testosterone concentration in diabetic male rats. PMID:28190818

  6. Treatment effects of Cardiotrophin-1 (CT-1) on streptozotocin-induced memory deficits in mice.

    PubMed

    Wang, Dongmei; Liu, Xiaozhuan; Liu, Yumei; Shen, Guomin; Zhu, Xiaoying; Li, Sanqiang

    2017-03-08

    Increasing evidence has shown that diabetes-associated cognitive impairment is correlated with mitochondrial dysfunction and resultant synaptic injury as well as brain insulin resistance. Cardiotrophin-1 (CT-1), a regulator of energy metabolism, has been shown to exhibit impressive neuroprotective effects. In this study, we evaluated the effects of CT-1 on brain pathological features in intracerebroventrical-streptozotocin (ICV-STZ)-treated mouse model, and explored its potential mechanisms. STZ was injected twice (3mg/kg, ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with CT-1 (1μg/day, ICV) starting from the first dose of STZ for 14days showed that CT-1 significantly improved learning and memory deficits, alleviated mitochondrial dysfunction, and increased synaptic density in the CA1 region of the hippocampus in ICV-STZ-treated mice. Moreover, CT-1 significantly enhanced insulin signaling pathway in the hippocampus of ICV-STZ-treated mice when compared with the control. However, all the protective effects including biochemistry, pathological changes and cognitive function could be blocked by an ICV injection of Compound C, a specific AMPK inhibitor. Taken together, these results suggested that CT-1 improves pathological changes and cognitive impairments via AMPK activation in ICV-STZ mice.

  7. Melatonin Reduces Cataract Formation and Aldose Reductase Activity in Lenses of Streptozotocin-induced Diabetic Rat

    PubMed Central

    Khorsand, Marjan; Akmali, Masoumeh; Sharzad, Sahab; Beheshtitabar, Mojtaba

    2016-01-01

    Background: The relationship between the high activity of aldose reductase (AR) and diabetic cataract formation has been previously investigated. The purpose of the present study was to determine the preventing effect of melatonin on streptozotocin (STZ)-induced diabetic cataract in rats. Methods: 34 adult healthy male Sprague-Dawely rats were divided into four groups. Diabetic control and diabetic+melatonin received a single dose of STZ (50 mg/kg, intraperitoneally), whereas the normal control and normal+melatonin received vehicle. The melatonin groups were gavaged with melatonin (5 mg/kg) daily for a period of 8 weeks, whereas the rats in the normal control and diabetic control groups received only the vehicle. The rats’ eyes were examined every week and cataract formation scores (0-4) were determined by slit-lamp microscope. At the end of the eighth week, the rats were sacrificed and markers of the polyol pathway and antioxidative (Glutathione, GSH) in their lens were determined. The levels of blood glucose, HbA1c and plasma malondialdhyde (MDA), as a marker of lipid peroxidation, were also measured. Results: Melatonin prevented STZ-induced hyperglycemia by decreased blood glucose and HbA1c levels. Slit lamp examination indicated that melatonin delayed cataract progression in diabetic rats. The results revealed that melatonin feeding increased the GSH levels, decreased the activities of AR and sorbitol dehydrogenase (SDH) and sorbitol formation in catractous lenses as well as plasma MDA content. Conclusion: In summary, for the first time we demonstrated that melatonin delayed the formation and progression of cataract in diabetic rat lenses. PMID:27365552

  8. Astaxanthin Inhibits Expression of Retinal Oxidative Stress and Inflammatory Mediators in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Yeh, Po-Ting; Huang, Hsin-Wei; Yang, Chung-May; Yang, Wei-Shiung; Yang, Chang-Hao

    2016-01-01

    Purpose We evaluated whether orally administered astaxanthin (AST) protects against oxidative damage in the ocular tissues of streptozotocin (STZ)-induced diabetic rats. Methods and Results Fifty 6-week-old female Wistar rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 40) or to remain uninduced (n = 10). The diabetic rats were randomly selected into four groups and they were separately administered normal saline, 0.6 mg/kg AST, 3 mg/kg AST, or 0.5 mg/kg lutein daily for eight weeks. Retinal functions of each group were evaluated by electroretinography. The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by immunohistochemistry, western blot analysis, ELISA, RT-PCR, and electrophoretic mobility shift assay (EMSA). Retinal functions were preserved by AST and lutein in different levels. Ocular tissues from AST- and lutein-treated rats had significantly reduced levels of oxidative stress mediators (8-hydroxy-2'-deoxyguanosine, nitrotyrosine, and acrolein) and inflammatory mediators (intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fractalkine), increased levels of antioxidant enzymes (heme oxygenase-1 and peroxiredoxin), and reduced activity of the transcription factor nuclear factor-kappaB (NF-κB). Conclusion The xanthophyll carotenoids AST and lutein have neuroprotective effects and reduce ocular oxidative stress, and inflammation in the STZ diabetic rat model, which may be mediated by downregulation of NF-κB activity. PMID:26765843

  9. Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract.

    PubMed

    Mediani, Ahmed; Abas, Faridah; Maulidiani, M; Khatib, Alfi; Tan, Chin Ping; Ismail, Intan Safinar; Shaari, Khozirah; Ismail, Amin; Lajis, N H

    2016-09-05

    Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus.

  10. Protective Action of Carica papaya on β-Cells in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Miranda-Osorio, Pedro H.; Castell-Rodríguez, Andrés E.; Vargas-Mancilla, Juan; Tovilla-Zárate, Carlos A.; Ble-Castillo, Jorge L.; Aguilar-Domínguez, Dora E.; Juárez-Rojop, Isela E.; Díaz-Zagoya, Juan C.

    2016-01-01

    The aim of the present study was to investigate the effect of C. papaya L. leaf extract (CPLE) on pancreatic islets in streptozotocin (STZ)-induced diabetic rats, as well as on cultured normal pancreatic cells with STZ in the medium. CPLE (3–125 mg/Kg) was administered orally for 20 days, while a group of diabetic rats received 5 IU/Kg/day of insulin. At the end of the treatment the rats were sacrificed. Blood was obtained to assess glucose and insulin levels. The pancreas was dissected to evaluate β cells by immunohistochemistry. In addition, normal pancreatic cells were cultured in a medium that included CPLE (3–12 mg). One half of the cultured cells received simultaneously CPLE and STZ (6 mg), while the other half received CPLE and five days later the STZ. After three days of incubation, insulin was assayed in the incubation medium. The CPLE administered to diabetic rats improved the fasting glycemia and preserved the number and structure of pancreatic islets. However, when CPLE was added to pancreatic cells in culture along with STZ, the insulin concentration was higher in comparison with the cells that only received STZ. In conclusion, the CPLE preserves the integrity of pancreatic islets, improves the basal insulin secretion and protects cultured cells from the adverse effects of STZ. PMID:27128930

  11. Antioxidant Effects of Fermented Red Ginseng Extracts in Streptozotocin- Induced Diabetic Rats

    PubMed Central

    Kim, Hyun-Jeong; Lee, Sung-Gyu; Chae, In-Gyeong; Kim, Mi-Jin; Im, Nam-Kyung; Yu, Mi-Hee; Lee, Eun-Ju; Lee, In-Seon

    2011-01-01

    The antioxidant activities of fermented red ginseng (FRG) were investigated in vitro and in vivo. The contents of total polyphenol and total flavonoid in FRG extracts were 17.01±2.00 μg/mg and 18.42±3.97 μg/mg, respectively. These extracts were capable of directly scavenging α, α-diphenyl-picrylhydrazyl free radicals. The antioxidative effects of the FRG extracts in streptozotocin (STZ)-induced diabetic rats were also investigated. The activities of plasma alanine transaminase, aspartate transaminase, and γ-glutamyltransferase were significantly decreased by extract administration as compared to an STZ control group. Hepatic glutathione content depleted by STZ treatment was significantly increased by treatment of the FRG extracts, but the elevation of lipid peroxide content induced by STZ was significantly decreased by the extracts. Activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase decreased after STZ-treatment were recovered by the treatment of the FRG extracts. These results indicate that FRG extracts have antioxidative effets in STZ-induced diabetic rats. PMID:23717054

  12. Changes in superoxide dismutase mRNA expression by streptozotocin-induced diabetes.

    PubMed Central

    Kamata, K.; Kobayashi, T.

    1996-01-01

    1. Experiments were designed to investigate the involvement of superoxide anions in the attenuated endothelium-dependent relaxation of the rat aorta from streptozotocin (STZ)-induced diabetic rats. 2. The endothelium-dependent relaxation responses to acetylcholine (ACh, 10(-7) M) in helical strips of the aorta precontracted with noradrenaline (NA, 5 x 10(-3) approximately 3 x 10(-7) M) were significantly decreased in STZ-induced diabetic rats. The recovery phase of the relaxation after single administration of ACh in the STZ-induced diabetic rats was more rapid than those in control vessels. 3. Preincubation of aortic strips with superoxide dismutase (SOD, 60 u ml-1) normalized the recovery phase of the relaxation of diabetic aorta after single administration of ACh, whereas catalase (150 u ml-1) or indomethacin (10(-5) M) had no effects on the relaxation. 4. SOD (180 u ml-1) caused relaxation in NA precontracted aortic strips and the degree of the SOD-induced relaxation was significantly greater in diabetic aorta as compared with age-matched control vessels. 5. When the changes in mRNA expressions of Mn-SOD or Cu-Zn-SOD were observed, Mn-SOD mRNA expression was markedly decreased, and Cu-Zn-SOD was slightly decreased in diabetic aorta. 6. These results suggest that the rapid destruction of NO by superoxide anions may occur in the STZ-induced diabetic rats, and this may be due to a decrease in mRNA expression of Mn-SOD or Cu-Zn-SOD. Images Figure 4 PMID:8894182

  13. Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract

    PubMed Central

    Patil, Madhoosudan A.; Suryanarayana, Palla; Putcha, Uday Kumar; Srinivas, Myadara

    2014-01-01

    Type 2 diabetes (T2D) generally follows prediabetes (PD) conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ) induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70%) of nSTZ injected pups developed IGT (nSTZ-PD) by two months but not cataract even after seven months, remaining (30%) nSTZ rats developed hyperglycemia (nSTZ-D) by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities. PMID:25505935

  14. Bacterial Flora Changes in Conjunctiva of Rats with Streptozotocin-Induced Type I Diabetes

    PubMed Central

    Qin, Yali; Luo, Dan; Yang, Shufei; Kou, Xinyun; Zi, Yingxin; Deng, Tingting; Jin, Ming

    2015-01-01

    Background The microbiota of both humans and animals plays an important role in their health and the development of disease. Therefore, the bacterial flora of the conjunctiva may also be associated with some diseases. However, there are no reports on the alteration of bacterial flora in conjunctiva of diabetic rats in the literature. Therefore, we investigated the changes in bacterial flora in bulbar conjunctiva of rats with streptozotocin (STZ)-induced type I diabetes. Methods A high dose of STZ (60 mg/kg, i.p.) was injected into Sprague-Dawley (SD) rats to induce type I diabetes mellitus (T1DM). The diabetic rats were raised in the animal laboratory and at 8 months post-injection of STZ swab samples were taken from the bulbar conjunctiva for cultivation of aerobic bacteria. The bacterial isolates were identified by Gram staining and biochemical features. The identified bacteria from both diabetic and healthy rats were then compared. Results The diabetic and healthy rats had different bacterial flora present in their bulbar conjunctiva. In total, 10 and 8 bacterial species were found in the STZ and control groups, respectively, with only three species (Enterococcus faecium, Enterococcus gallinarum and Escherichia coli) shared between the two groups. Gram-positive bacteria were common in both groups and the most abundant was Enterococcus faecium. However, after the development of T1DM, the bacterial flora in the rat bulbar conjunctiva changed considerably, with a reduced complexity evident. Conclusions STZ-induced diabetes caused alterations of bacterial flora in the bulbar conjunctiva in rats, with some bacterial species disappearing and others emerging. Our results indicate that the conjunctival bacterial flora in diabetic humans should be surveyed for potential diagnostic markers or countermeasures to prevent eye infections in T1DM patients. PMID:26176548

  15. Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats.

    PubMed

    Paterniti, Irene; Di Paola, Rosanna; Campolo, Michela; Siracusa, Rosalba; Cordaro, Marika; Bruschetta, Giuseppe; Tremolada, Gemma; Maestroni, Anna; Bandello, Francesco; Esposito, Emanuela; Zerbini, Gianpaolo; Cuzzocrea, Salvatore

    2015-12-15

    Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR.

  16. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg-1 body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes. PMID:26261706

  17. Protective effect of polysaccharides from Opuntia dillenii Haw. fruits on streptozotocin-induced diabetic rats.

    PubMed

    Gao, Jie; Han, Yu-Lu; Jin, Zheng-Yu; Xu, Xue-Ming; Zha, Xue-Qiang; Chen, Han-Qing; Yin, Yan-Yan

    2015-06-25

    In this study, a novel water-soluble polysaccharide fraction with molecular weight of 6479.1kDa was isolated from the fruits of Opuntia dillenii Haw., which consisted of rhamnose, xylose, mannose and glucose in the molar ratio of 14.99:1.14:1.00:6.47. The protective effect of O. dillenii Haw. fruits polysaccharide (ODFP) against oxidative damage in streptozotocin (STZ)-induced diabetic rats was investigated. The results showed that oral administration of ODFP significantly decreased food intake, water intake, urine production, organ weights and blood glucose level, and increased body weight in STZ-induced diabetic rats. ODFP also significantly increased the activities of SOD, GPx and CAT, and decreased malondialdehyde level in serum, liver, kidney, and pancreas in STZ-induced diabetic rats. Moreover, histopathological examination showed that ODFP could markedly improve the structure integrity of pancreatic islet tissue in STZ-induced diabetic rats. These results suggest that ODFP have hypoglycemic and antioxidant properties and can protect rats from STZ-induced oxidative damage.

  18. Betaine inhibits vascularization via suppression of Akt in the retinas of streptozotocin-induced hyperglycemic rats

    PubMed Central

    KIM, YOUNG-GIUN; LIM, HYUNG-HO; LEE, SUH-HA; SHIN, MAL-SOON; KIM, CHANG-JU; YANG, HYEON JEONG

    2015-01-01

    Diabetic retinopathy is a severe microvascular complication amongst patients with diabetes, and is the primary cause of visual loss through neovascularization. Betaine is one of the components of Fructus Lycii. In the present study, the effects of betaine on the expression levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α in association with the Akt pathway were investigated in the retinas of streptozotocin (STZ)-induced diabetic rats using western blot and immunohistochemical analyses. The results of the present study revealed that the expression levels of VEGF, HIF-1α, and Akt were increased in the retinas of the STZ-induced diabetic rats. Betaine treatment attenuated this increase in VEGF and HIF-1α expression via suppression of diabetes-induced Akt activation in the retinas of the diabetic rats. The results suggested that betaine may potentially be used to delay the onset of complications associated with diabetic retinopathy via inhibition of retinal neovascularization in patients with diabetes. PMID:25891515

  19. Study on The Effect of Royal Jelly on Reproductive Parameters in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ghanbari, Elham; Nejati, Vahid; Najafi, Gholamreza; Khazaei, Mozafar; Babaei, Mohammad

    2015-01-01

    Background Diabetes mellitus has a variety of structural and functional effects on the male reproductive system. Diabetes results in reduced sperm parameters and libido. The present study aims to investigate the effects of royal jelly (RJ) on reproductive parameters of testosterone and malondialdehyde (MDA) production in diabetic rats. Materials and Methods This experimental study was conducted on adult male Wistar rats. The animals were divided into four groups (n=8 per group): control, RJ, diabetic and diabetic treated with RJ. Diabetes was induced by intraperitoneal injection of 60 mg/kg body weight (BW) of streptozotocin (STZ). RJ, at a dose of 100 mg/kg BW was given by gavage. The duration of treatment was six weeks. After the treatment period the rats were sacrificed. The testes were weighed and changes in sperm count, motility, viability, deformity, DNA integrity and chromatin quality were analyzed. Serum testosterone and MDA concentrations of testicular tissue were determined. Data were analyzed by oneway ANOVA with p<0.05 as the significant level. Results STZ-induced diabetes decreased numerous reproductive parameters in rats. Testicular weight, sperm count, motility, viability and serum testosterone levels increased in the diabetic group treated with RJ. There was a significant decrease observed in sperm deformity, DNA integrity, chromatin quality, and tissue MDA levels in diabetic rats treated with RJ compared to the diabetic group (p<0.05). Conclusion RJ improved reproductive parameters such as testicular weight, sperm count, viability, motility, deformity, DNA integrity, chromatin quality, serum testosterone and testicular tissue MDA levels in diabetic rats. PMID:25918599

  20. Hypoglycemic Effect of Jicama (Pachyrhizus erosus) Extract on Streptozotocin-Induced Diabetic Mice.

    PubMed

    Park, Chan Joo; Han, Ji-Sook

    2015-06-01

    The purpose of this research was to investigate the inhibitory effect of jicama extract on α-glucosidase activity, α-amylase activity, and postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. Jicama extract showed prominent inhibitory effects against α-glucosidase and α-amylase. The IC50 values of jicama extract against α-glucosidase and α-amylase were 0.083±0.004 and 0.091±0.017 mg/mL, respectively. The increase in postprandial blood glucose levels was more significantly suppressed in the jicama extract-administered group than in the control group of both STZ-induced diabetic and normal mice. Blood glucose levels of the control group increased to 383.75±11.54 and 402.50±15.32 mg/dL at 30 and 60 min after a meal and decreased to 349.67±11.62 mg/dL at 120 min. However, postprandial blood glucose levels were significantly decreased, when diabetic mice were fed with jicama extract (342.00±15.73, 367.00±13.00, and 329.67±12.43 mg/dL at 30, 60, and 120 min, respectively). Furthermore, the area under the curve was significantly decreased with jicama extract administration in diabetic mice (P<0.05). Therefore, these results indicate that jicama extract may help decrease postprandial blood glucose level by inhibiting α-glucosidase.

  1. Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats

    PubMed Central

    Yeom, Eunseop; Byeon, Hyeokjun; Lee, Sang Joon

    2016-01-01

    Diabetes mellitus with abnormal glucose concentration is associated with changes in hemorheological properties, endothelial function, and platelets hyperactivity. Disturbances may significantly be responsible for diabetes-related vascular complications. In this study, hemorheological and hemodynamic properties were measured according to diabetic duration after streptozotocin treatment in rats. For ex vivo measurements, an extracorporeal model was adopted. Flow rate and blood viscosity were measured using a microfluidic device. Erythrocyte aggregation and morphological parameters of erythrocytes were measured by modified erythrocyte sedimentation rate and the phase-contrast holography under in vitro conditions. The platelet aggregation and mean pressure in the femoral artery were estimated under ex vivo conditions. Hemorheological properties including blood viscosity, erythrocyte aggregation and shape parameters for the control group are significantly different with those for diabetic groups. The changes with respect to diabetic duration were relatively unnoticeable. However, the platelet aggregation is strongly dependent on the diabetic duration. Based on these results, hyperglycemia exposure may induce hemorheological variations in early stages of diabetes mellitus. High platelet aggregation may become more pronounced according to the diabetic duration caused by variations in hemorheological properties resulting in endothelial dysfunction. This study would be helpful in understanding the effects of diabetic duration on biophysical properties. PMID:26898237

  2. The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells.

    PubMed

    Paviolo, Natalia S; Santiñaque, Federico F; Castrogiovanni, Daniel C; Folle, Gustavo A; Bolzán, Alejandro D

    2015-12-01

    We analyzed chromosomal aberrations involving telomeres in the progeny of mammalian cells exposed to the methylating agent and antineoplastic/diabetogenic drug streptozotocin (STZ), to test whether it induces long-term telomere instability (by chromosome end loss and/or telomere dysfunction). Rat cells (ADIPO-P2 cell line, derived from Sprague-Dawley rat adipose cells) were treated with a single concentration of STZ (2mM). Chromosomal aberrations were analyzed 18h, 10 days, and 15 days after treatment, using PNA-FISH with a pan-telomeric probe [Cy3-(CCCTAA)3] to detect (TTAGGG)n repeats. Cytogenetic analysis revealed a higher frequency of chromosomal aberrations in STZ-exposed cultures vs. untreated cultures at each time point analyzed. The yield of induced aberrations was very similar at each time point. Induction of aberrations not involving telomere dysfunction was only observed 18h and 15 days after treatment, whereas induction of telomere dysfunction-related aberrations by STZ (mainly in the form of telomere FISH signal loss and duplications, most of them chromatid-type aberrations) was observed at each time point. Our results show that STZ induces persistent telomere instability in mammalian cells, cytogenetically manifested as telomere dysfunction-related chromosomal aberrations. Neither telomere length nor telomerase activity is related to the telomere dysfunction.

  3. Urtica dioica modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice.

    PubMed

    Patel, Sita Sharan; Gupta, Sahil; Udayabanu, Malairaman

    2016-06-01

    Diabetes mellitus has been associated with functional abnormalities in the hippocampus and performance of cognitive function. Urtica dioica (UD) has been used in the treatment of diabetes. In our previous report we observed that UD extract attenuate diabetes mediated associative and spatial memory dysfunction. The present study aimed to evaluate the effect of UD extract on mouse model of diabetes-induced recognition memory deficit and explore the possible mechanism behind it. Streptozotocin (STZ) (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes followed by UD extract (50 mg/kg, oral) or rosiglitazone (ROSI) (5 mg/kg, oral) administration for 8 weeks. STZ induced diabetic mice showed significant decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane resulting in cognitive dysfunction and hypolocomotion. UD treatment effectively improved hippocampal insulin signaling, glucose tolerance and recognition memory performance in diabetic mice, which was comparable to ROSI. Further, diabetes mediated oxidative stress and inflammation was reversed by chronic UD or ROSI administration. UD leaves extract acts via insulin signaling pathway and might prove to be effective for the diabetes mediated central nervous system complications.

  4. Beneficial effects of quercetin on sperm parameters in streptozotocin-induced diabetic male rats.

    PubMed

    Khaki, Arash; Fathiazad, Fatemeh; Nouri, Mohammad; Khaki, Amirafshin; Maleki, Navid A; Khamnei, Hossein Jabbari; Ahmadi, Porya

    2010-09-01

    Quercetin (QR) is a strong antioxidant and has been shown to reduce oxidative stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in animal models. Antioxidants have significant effects on spermatogenesis, sperm biology and oxidative stress, and changes in antioxidant capacity are considered to be involved in the pathogenesis of chronic diabetes mellitus. The present study aims to examine the influence of QR on spermatogenesis in STZ-induced diabetes in male Wistar rats. Animals (n = 50) were allocated into five groups: Group 1: Control rats given 0.5 ml of 20% glycerol in 0.9% normal saline. Group 2: Control rats given buffer (pH4.0).Group 3: diabetic controls. Group 4: rats given QR 15 mg/kg/day (i.p.). Group 5: STZ + QR rats. Animals were kept in standard conditions. At the end of the experiment (28th day), blood samples were taken for determination of testosterone, total antioxidant capacity, and levels of malondialdehyde and oxidized low-density lipoprotein. All rats were euthanized, testes were dissected out and spermatozoa were collected from the epididymis for analysis. Sperm numbers, percentages of sperm viability and motility, and total serum testosterone increased significantly in QR-treated diabetic rats (P < 0.05) compared with control groups. In histopathology, degeneration and inflammation in testes cells associated with diabetes were improved and testes weights in the QR-treated diabetic group decreased significantly in comparison with controls (P < 0.05). We conclude that QR has significant beneficial effects on the sperm viability, motility, and serum total testosterone and could be effective for maintaining healthy sperm parameters and male reproductive function in diabetic rats.

  5. Increased melatonin synthesis in pineal glands of rats in streptozotocin induced type 1 diabetes.

    PubMed

    Peschke, Elmar; Wolgast, Sabine; Bazwinsky, Ivonne; Pönicke, Klaus; Muhlbauer, Eckhard

    2008-11-01

    It is well-documented that melatonin influences insulin secretion. The effects are mediated by specific, high-affinity, pertussis-toxin-sensitive, G protein-coupled membrane receptors (MT(1) as well MT(2)), which are present in both the pancreatic tissue and islets of rats and humans, as well as in rat insulinoma cells (INS1). Via the Gi-protein-adenylatecyclase-3',5'-cyclic adenosine monophosphate (cAMP) and, possibly, the guanylatecyclase-cGMP pathways, melatonin decreases insulin secretion, whereas, by activating the Gq-protein-phospholipase C-IP(3) pathway, it has the opposite effect. For further analysis of the interactions between melatonin and insulin, diabetic rats were investigated with respect to melatonin synthesis in the pineal gland and plasma insulin levels. In this context, recent investigations have proven that type 2 diabetic rats and humans display decreased melatonin levels, whereas type 1 diabetic IDDM rats or those with diabetes induced by streptozotocin (STZ) of the present study show increased plasma melatonin levels and elevated AA-NAT-mRNA. Furthermore, the mRNA of pineal insulin receptors and beta1-adrenoceptors, including the clock genes Per1 and Bmal1 and the clock-controlled output gene Dbp, increases in both young and middle-aged STZ rats. The results therefore indicate that the decreased insulin levels in STZ-induced type 1 diabetes are associated with higher melatonin plasma levels. In good agreement with earlier investigations, it was shown that the elevated insulin levels observed in type 2 diabetes, are associated with decreased melatonin levels. The results thus prove that a melatonin-insulin antagonism exists. Astonishingly, notwithstanding the drastic metabolic disturbances in STZ-diabetic rats, the diurnal rhythms of the parameters investigated are maintained.

  6. Hepatoprotective effects of melatonin against pronecrotic cellular events in streptozotocin-induced diabetic rats.

    PubMed

    Grigorov, Ilijana; Bogojević, Desanka; Jovanović, Sofija; Petrović, Anja; Ivanović-Matić, Svetlana; Zolotarevski, Lidija; Poznanović, Goran; Martinović, Vesna

    2014-06-01

    Oxidative stress-mediated damage to liver tissue underlies the pathological alterations in liver morphology and function that are observed in diabetes. We examined the effects of the antioxidant action of melatonin against necrosis-inducing DNA damage in hepatocytes of streptozotocin (STZ)-induced diabetic rats. Daily administration of melatonin (0.2 mg/kg) was initiated 3 days before diabetes induction and maintained for 4 weeks. Melatonin-treated diabetic rats exhibited improved markers of liver injury (P < 0.05), alkaline phosphatase, and alanine and aspartate aminotransferases. Melatonin prevented the diabetes-related morphological deterioration of hepatocytes, DNA damage (P < 0.05), and hepatocellular necrosis. The improvement was due to containment of the pronecrotic oxygen radical load, observed as inhibition (P < 0.05) of the diabetes-induced rise in lipid peroxidation and hydrogen peroxide increase in the liver. This was accompanied by improved necrotic markers of cellular damage: a significant reduction in cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1) into necrotic 55- and 62-kDa fragments, and inhibition of nucleus-to-cytoplasm translocation and accumulation in the serum of the high-mobility group box 1 (HMGB1) protein. We conclude that melatonin is hepatoprotective in diabetes. It reduces extensive DNA damage and resulting necrotic processes. Melatonin application could thus present a viable therapeutic option in the management of diabetes-induced liver injury.

  7. Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats.

    PubMed

    Elbe, H; Esrefoglu, M; Vardi, N; Taslidere, E; Ozerol, E; Tanbek, K

    2015-09-01

    In this study, effects of melatonin, quercetin and resveratrol on hepatocellular injury in streptozotocin (STZ)-induced experimental diabetes were aimed to be investigated by histological and biochemical methods. Thirty-five male Wistar albino rats were divided into five groups, namely, control, diabetes (STZ 45 mg/kg/single dose/intraperitoneally (ip)), diabetes + melatonin (10 mg/kg/30 days/ip), diabetes + quercetin (25 mg/kg/30 days/ip) and diabetes + resveratrol (10 mg/kg/30 days/ip). Initial and final blood glucose levels and body weights (BWs) were measured. At the end of the experimentation, following routine tissue processing procedure, sections were stained with haematoxylin-eosin (H-E), periodic acid Schiff and Masson's trichrome. Tissue malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were examined. The diabetic rats had significantly higher blood glucose levels than those of control rats (p = 0.0001). Mean BWs of diabetic rats were significantly decreased when compared with the control rats (p = 0.0013). Histopathological alterations including cellular glycogen depletion, congestion, sinusoidal dilatation, inflammation and fibrosis were detected in diabetes group. On the other hand, histopathological changes markedly reduced in all of the treatment groups (p = 0.001). Mean tissue MDA level was increased but mean tissue CAT and SOD activities and GSH levels were decreased in the diabetes group. Melatonin, quercetin and resveratrol administered diabetic rats showed an increase in CAT activities and GSH levels and a decrease in MDA levels (p < 0.05, for all). Melatonin, quercetin and resveratrol administrations markedly reduced hepatocellular injury in STZ-induced experimental diabetes.

  8. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats.

    PubMed

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg(-1) body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes.

  9. Antioxidant effect of Ajuga iva aqueous extract in streptozotocin-induced diabetic rats.

    PubMed

    Taleb-Senouci, D; Ghomari, H; Krouf, D; Bouderbala, S; Prost, J; Lacaille-Dubois, M A; Bouchenak, M

    2009-06-01

    The purpose of this study was to investigate the possible antioxidant effect of an aqueous extract of Ajuga iva (Ai) in streptozotocin (STZ)-induced diabetic rats. Twelve diabetic rats were divided into two groups fed a casein diet supplemented or not with Ai (0.5%), for 4 weeks. In vitro, the Ai extract possessed a very high antioxidant effect (1 mg/ml was similar to those of trolox 300 mmol/l). The results indicated that plasma thiobarbituric acid reactive substances (TBARS) values were reduced by 41% in Ai-treated compared with untreated diabetic rats. TBARS concentrations were lower 1.5-fold in liver, 1.8-fold in heart, 1.9-fold in muscle and 2.1-fold in brain in Ai-treated than untreated group. In erythrocytes, Ai treatment increased significantly the activities of glutathione peroxidase (GSH-Px) (+25%) and glutathione reductase (GSSH-Red) (+22%). Superoxide dismutase activity was increased in muscle (+22%), while GSH-Px activity was significantly higher in liver (+28%), heart (+40%) and kidney (+45%) in Ai-treated compared with untreated group. Liver and muscle GSSH-Red activity was, respectively, 1.6- and 1.5-fold higher in Ai-treated than untreated diabetic group. Catalase activity was significantly increased in heart (+36%) and brain (+32%) in Ai-treated than untreated group. Ai treatment decreased plasma nitric oxide (-33%), carbonyls (-44%) and carotenoids (-68%) concentrations. In conclusion, this study indicates that Ajuga iva aqueous extract improves the antioxidant status by reducing lipid peroxidation and enhancing the antioxidant enzymes activities in plasma, erythrocytes and tissues of diabetic rats.

  10. Hypoglycemic Effect of Jicama (Pachyrhizus erosus) Extract on Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Park, Chan Joo; Han, Ji-Sook

    2015-01-01

    The purpose of this research was to investigate the inhibitory effect of jicama extract on α-glucosidase activity, α-amylase activity, and postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. Jicama extract showed prominent inhibitory effects against α-glucosidase and α-amylase. The IC50 values of jicama extract against α-glucosidase and α-amylase were 0.083±0.004 and 0.091±0.017 mg/mL, respectively. The increase in postprandial blood glucose levels was more significantly suppressed in the jicama extract-administered group than in the control group of both STZ-induced diabetic and normal mice. Blood glucose levels of the control group increased to 383.75±11.54 and 402.50±15.32 mg/dL at 30 and 60 min after a meal and decreased to 349.67±11.62 mg/dL at 120 min. However, postprandial blood glucose levels were significantly decreased, when diabetic mice were fed with jicama extract (342.00±15.73, 367.00±13.00, and 329.67±12.43 mg/dL at 30, 60, and 120 min, respectively). Furthermore, the area under the curve was significantly decreased with jicama extract administration in diabetic mice (P<0.05). Therefore, these results indicate that jicama extract may help decrease postprandial blood glucose level by inhibiting α-glucosidase. PMID:26175995

  11. Augmented insulin effects on plasma glucose by cranberry procyanidins in streptozotocin-induced diabetic rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives of this study were to determine if cranberry proanthocyanidins (CPACs) had an antihyperglycemic effect in the presence or absence of insulin in male diabetic Sprague-Dawley rats. Rats (approximately 250 g)(n=6-10/ trt) were given a single intraperitoneal (ip) injection of freshly prepared...

  12. Dimethyl fumarate attenuates intracerebroventricular streptozotocin-induced spatial memory impairment and hippocampal neurodegeneration in rats.

    PubMed

    Majkutewicz, Irena; Kurowska, Ewelina; Podlacha, Magdalena; Myślińska, Dorota; Grembecka, Beata; Ruciński, Jan; Plucińska, Karolina; Jerzemowska, Grażyna; Wrona, Danuta

    2016-07-15

    Intracerebroventricular (ICV) injection of streptozotocin (STZ) is a widely-accepted animal model of sporadic Alzheimer's disease (sAD). The present study evaluated the ability of dimethyl fumarate (DMF), an agent with antioxidant and anti-inflammatory properties, to prevent spatial memory impairments and hippocampal neurodegeneration mediated by ICV injection of STZ in 4-month-old rats. Rodent chow containing DMF (0.4%) or standard rodent chow was made available on day 0. Rat body weight and food intake were measured daily for whole the experiment (21days). STZ or vehicle (SHAM) ICV injections were performed on days 2 and 4. Spatial reference and working memory were evaluated using the Morris water maze on days 14-21. Cells containing Fluoro-Jade B (neurodegeneration marker), IL-6, IL-10 were quantified in the hippocampus and choline acetyltransferase (ChAT) in the basal forebrain. The disruption of spatial memory and a high density of hippocampal CA1-3 cells labeled with Fluoro-Jade B or containing IL-6 or IL-10 were observed in the STZ group but not in the STZ+DMF group, as compared to the SHAM or SHAM+DMF groups. STZ vs. STZ+DMF differences were found: worse reference memory acquisition, fewer ChAT-positive neurons in the medial septum (Ch1), more Fluoro-Jade-positive CA1 hippocampal cells in STZ rats. DMF therapy in a rodent model of sAD prevented the disruption of spatial reference and working memory, loss of Ch1 cholinergic cells and hippocampal neurodegeneration as well as the induction of IL-6 and IL-10 in CA1. These beneficial cognitive and molecular effects validate the anti-inflammatory and neuroprotective properties of DMF in the hippocampus.

  13. Embelin Attenuates Intracerebroventricular Streptozotocin-Induced Behavioral, Biochemical, and Neurochemical Abnormalities in Rats.

    PubMed

    Arora, Rimpi; Deshmukh, Rahul

    2016-10-15

    Embelin, the main active constituent of Embelia ribes, has been reported to possess various pharmacological actions, including anti-inflammatory, antioxidant, anticonvulsant, and neuroprotective. The present study was designed to investigate neuroprotective mechanisms and therapeutic potential of embelin against intracerebroventricular streptozotocin (ICV-STZ)-induced experimental sporadic dementia in rats. STZ was infused bilaterally at the dose of (3 mg/kg/1 μl/1 min) ICV on day first and third. Spatial and non-spatial memory was evaluated using Morris water maze and object recognition task in rats. Embelin (2.5, 5, and 10 mg/kg, i.p.) was administrated for 14 days from seventh day onwards after first ICV-STZ infusion in rats. On day 22, rats were sacrificed and hippocampal brain regions were used to identify biochemical, neurochemical, and neuroinflammatory alterations. STZ-infused rats showed significant learning and memory deficit which was associated with an increase in oxidative stress (lipid peroxidation and nitrite), compromised antioxidant defense (reduced glutathione), neurotransmitter alterations (AChE, dopamine, noradrenaline, 5-hydroxytryptamine, gama amino butyric acid, and glutamate), and elevation in neuroinflammatory cytokine (IL-1 β, IL-6, and TNF-α) levels. Embelin dose dependently attenuated STZ-induced cognitive deficit and biochemical alterations and restored hippocampal neurochemical levels. The observed protective effect might be attributed to the antioxidant and anti-inflammatory potential of embelin and its ability to restore hippocampal neurochemistry. Thus, the outcomes of the current study suggest therapeutic potential of embelin in cognitive disorders such as sporadic Alzheimer's disease (SAD).

  14. Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats.

    PubMed

    Lee, Unji; Lee, Inchul; Lee, Byung K; Kang, Hee E

    2013-11-20

    Metoprolol is a selective β1-adrenergic receptor antagonist metabolized by hepatic cytochrome P450s (CYPs). In this study, we evaluated pharmacokinetic changes following intravenous (i.v.) and oral metoprolol in rats with diabetes mellitus induced by streptozotocin (DMIS). Metoprolol has an intermediate hepatic extraction ratio in rats (0.586-0.617), and it is assumed that the liver is exclusively responsible for metoprolol metabolism. Thus, the hepatic clearance, CL(H) (the non-renal clearance, CL(NR)) of metoprolol depends on the hepatic blood flow rate (Q(H)), the free fraction in plasma (f(p)), and in vitro hepatic intrinsic clearance, CL(int). After i.v. administration of 1.5 mg/kg metoprolol to DMIS rats, its CLNR was 40.9% faster than control animals. This could be due to a significantly faster QH because hepatic CL(int) and fp were comparable between the two groups of rats due to unchanged hepatic CYP2D activity. After oral administration of 1.5 mg/kg metoprolol to DMIS rats, gastrointestinal absorption was >99% of the oral dose for both groups, while the area under the curve (AUC) was 27.9% smaller, which could be caused by the greater hepatic metabolism seen in the i.v. study. These findings have potential therapeutic implications, assuming that the DMIS rats qualitatively reflect similar changes in patients with diabetes.

  15. Antidiabetic activity of Artemisia amygdalina Decne in streptozotocin induced diabetic rats.

    PubMed

    Ghazanfar, Khalid; Ganai, Bashir A; Akbar, Seema; Mubashir, Khan; Dar, Showkat Ahmad; Dar, Mohammad Younis; Tantry, Mudasir A

    2014-01-01

    Artemisia species have been extensively used for the management of diabetes in folklore medicine. The current study was designed to investigate the antidiabetic and antihyperlipidemic effects of Artemisia amygdalina. Petroleum ether, ethyl acetate, methanol, and hydroethanolic extracts of Artemisia amygdalina were tested for their antidiabetic potentials in diabetic rats. The effect of extracts was observed by checking the biochemical, physiological, and histopathological parameters in diabetic rats. The hydroethanolic and methanolic extracts each at doses of 250 and 500 mg/kg b. w significantly reduced glucose levels in diabetic rats. The other biochemical parameters like cholesterol, triglycerides, low density lipoproteins (LDL), serum creatinine, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatise (ALP), were found to be reduced by the hydroethanolic and methanolic extracts. The extracts also showed reduction in the feed and water consumption of diabetic rats when compared with the diabetic control. The histopathological results of treated groups showed the regenerative/protective effect on β -cells of pancreas in diabetic rats. The current study revealed the antidiabetic potential of Artemisia amygdalina being effective in hyperglycemia and that it can effectively protect against other metabolic aberrations caused by diabetes in rats, which seems to validate its therapeutic traditional use.

  16. Neural Degeneration in the Retina of the Streptozotocin-Induced Type 1 Diabetes Model

    PubMed Central

    Ozawa, Yoko; Kurihara, Toshihide; Sasaki, Mariko; Ban, Norimitsu; Yuki, Kenya; Kubota, Shunsuke; Tsubota, Kazuo

    2011-01-01

    Diabetic retinopathy, a vision-threatening disease, has been regarded as a vascular disorder. However, impaired oscillatory potentials (OPs) in the electroretinogram (ERG) and visual dysfunction are recorded before severe vascular lesions appear. Here, we review the molecular mechanisms underlying the retinal neural degeneration observed in the streptozotocin-(STZ-) induced type 1 diabetes model. The renin-angiotensin system (RAS) and reactive oxygen species (ROS) both cause OP impairment and reduced levels of synaptophysin, a synaptic vesicle protein for neurotransmitter release, most likely through excessive protein degradation by the ubiquitin-proteasome system. ROS also decrease brain-derived neurotrophic factor (BDNF) and inner retinal neuronal cells. The influence of both RAS and ROS on synaptophysin suggests that RAS-ROS crosstalk occurs in the diabetic retina. Therefore, suppressors of RAS or ROS, such as angiotensin II type 1 receptor blockers or the antioxidant lutein, respectively, are potential candidates for neuroprotective and preventive therapies to improve the visual prognosis. PMID:22144984

  17. Effect of vitamin D on aortic remodeling in streptozotocin-induced diabetes

    PubMed Central

    2012-01-01

    Background Diabetes mellitus is associated with micro- and macrovascular complications and increased cardiovascular risk. Elevated levels of serum asymmetric dimethylarginine (ADMA) may be responsible for endothelial dysfunction associated with diabetes-induced vascular impairment. Vitamin D may have potential protective effects against arterial stiffening. This study aimed to examine both the effects of diabetes on the functional/structural properties of the aorta and the endothelial function and the effects of vitamin D supplementation. Methods Male Wistar rats (n = 30) were randomly assigned to control untreated, diabetic untreated, and diabetic + cholecalciferol groups. Diabetes was induced by intraperitoneal injection of streptozotocin, followed by oral administration of cholecalciferol (500 IU/kg) for 10 weeks in the treatment group. Aortic pulse wave velocity (PWV) was recorded over a mean arterial pressure (MAP) range of 50 to 200 mmHg using a dual pressure sensor catheter. Intravenous infusion of phenylephrine and nitroglycerine was used to increase and decrease MAP, respectively. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using a radioimmune assay. ADMA levels in serum were measured by enzyme-linked immunoassay. Aortic samples were collected for histomorphometrical analysis. Results PWV up to MAP 170 mmHg did not reveal any significant differences between all groups, but in diabetic rats, PWV was significantly elevated across MAP range between 170 and 200 mmHg. Isobaric PWV was similar between the treated and untreated diabetic groups, despite significant differences in the levels of serum 25(OH)D (493 ± 125 nmol/L vs 108 ± 38 nmol/L, respectively). Serum levels of ADMA were similarly increased in the treated and untreated diabetic groups, compared to the control group. The concentration and integrity of the elastic lamellae in the medial layer of the aorta was impaired in untreated diabetic rats and improved by vitamin D supplementation. Conclusion PWV profile determined under isobaric conditions demonstrated differential effects of uncontrolled diabetes on aortic stiffness. Diabetes was also associated with elevated serum levels of ADMA. Vitamin D supplementation did not improve the functional indices of aortic stiffness or endothelial function, but prevented the fragmentation of elastic fibers in the aortic media. PMID:22631050

  18. Targeting heme oxygenase-1 in early diabetic nephropathy in streptozotocin-induced diabetic rats.

    PubMed

    Abo El Gheit, R; Emam, M N

    2016-12-01

    Diabetic nephropathy (DN) is one of the most common microvascular diabetic complications. This study was designed to evaluate the possible protective effect and underlying mechanisms of HO-1 induction in streptozotocin (STZ)-induced early DN in rats. The diabetic rats were divided into three groups: STZ-diabetic, cobalt protoporphyrin (CoPP)-treated diabetic, and zinc protoporphyrin IX (ZnPP)-treated diabetic groups. Compared to the STZ-diabetic group, CoPP-induced HO-1 upregulation improved the diabetic state and renal functional parameters, suppressed the renal proinflammatory marker, NF-κB, abrogated the elevated renal hydroxyprolin, and decreased the enhanced renal nicotinamide adenine dinucleotide phosphate oxidase activity with parallel reduction of urinary oxidative stress markers. On the contrary, treatment with ZnPP abrogated HO-1 levels, aggravated the diabetic condition with further increases in renal oxidative stress, fibrotic and inflammatory markers, and exacerbated renal dysfunction in diabetic animals. These findings suggest that the reduced diabetic renal injury upon HO-1 induction implicates the role of HO-1 induction as a potential treatment for DN.

  19. Antihyperglycemic and antioxidative potential of Matricaria chamomilla L. in streptozotocin-induced diabetic rats.

    PubMed

    Cemek, Mustafa; Kağa, Sadik; Simşek, Nejdet; Büyükokuroğlu, Mehmet Emin; Konuk, Muhsin

    2008-07-01

    Plants with antidiabetic activities provide important sources for the development of new drugs in the treatment of diabetes mellitus. In the present study, we investigated possible antihyperglycemic and antioxidative activities of the aerial part of the Matricaria chamomilla L. ethanolic extract (MCE) in streptozotocin (STZ; 70 mg/kg, i.p.)-induced diabetic rats. The following groups were assigned; sham (did not receive any substance), STZ + distilled water (control), STZ + 5 mg/kg glibenclamide, STZ + 20 mg/kg MCE, STZ + 50 mg/kg MCE, STZ + 100 mg/kg MCE. Diabetic rats were treated for 14 days by gavage. Postprandial blood glucose levels, malondialdehyde, reduced glutathione (GSH), nitrate, nitrite, ascorbic acid, retinol, beta-carotene, superoxide dismutase, and catalase levels were measured, and immunohistochemical studies were performed in all of the groups. The obtained data showed that STZ resulted in oxidative stress and affected the antioxidant status. Treatment with different doses of MCE significantly reduced postprandial hyperglycemia and oxidative stress, and augmented the antioxidant system. In histological investigations, MCE treatment protected the majority of the pancreatic islet cells, with respect to the control group. As a result, MCE exhibited significant antihyperglycemic effect and protected beta-cells in STZ-diabetic rats, in a dose-dependent manner, and diminished the hyperglycemia-related oxidative stress.

  20. Antioxidant enzymatic defense in salivary glands of streptozotocin-induced diabetic rats: a temporal study.

    PubMed

    Ibuki, Flavia Kazue; Simões, Alyne; Nogueira, Fernando Neves

    2010-08-01

    Hyperglycemia induces overproduction of superoxide and it is related to diabetic complications. In this study, we analyzed the antioxidant enzymatic defense and the lipid peroxidation of rat salivary glands in six different periods of diabetic condition. Ninety-six rats were divided into 12 groups: C7/14/21/28/45/60 (non-diabetic animals) and D7/14/21/28/45/60 (diabetic animals). Diabetes was induced by streptozotocin and the rats were euthanized after 7, 14, 21, 28, 45, or 60 days. Their parotid (PA) and submandibular (SM) glands were removed soon after the sacrifice and the total protein and malondialdehyde (MDA) concentrations, as well as, the superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities were determined. Twenty-one days after the diabetes induction, the SM glands showed an increase in SOD, CAT, and GPx activities, as well as, MDA concentration. Concerning the PA glands, an increase in the CAT activity and MDA content was observed throughout the observation period. The results suggest that diabetes can cause alterations on the salivary glands and that PA and SM glands react differently when exposed to diabetes condition. However, no impairment of antioxidant system was observed in the group whose diabetic condition had been induced 60 days earlier, herein named 60-day group.

  1. Blunted Respiratory Responses in the Streptozotocin-Induced Alzheimer's Disease Rat Model.

    PubMed

    Ebel, Dalton L; Torkilsen, Christopher G; Ostrowski, Tim D

    2017-01-01

    Alzheimer's disease (AD) is known for the progressive decline of cognition and memory. In addition to these disease-defining symptoms, impairment of respiratory function is frequently observed and often expressed by sleep-disordered breathing or reduced ability to adjust respiration when oxygen demand is elevated. The mechanisms for this are widely unknown. Postmortem analysis from the brainstem of AD patients reveals pathological alterations, including in nuclei responsible for respiratory control. In this study, we analyzed respiratory responses and morphological changes in brainstem nuclei following intracerebroventricular (ICV) injections of streptozotocin (STZ), a rat model commonly used to mimic sporadic AD. ICV-STZ induced significant astrogliosis in the commissural part of the nucleus tractus solitarii, an area highly involved in respiration control. The astrogliosis was identified by a significant increase in S100B-immunofluorescence that is similar to the astrogliosis found in the CA1 region of the hippocampus. Using plethysmography, the control group displayed a typical age-dependent decrease of ventilation that was absent in the STZ rat group. This is indicative of elevated minute ventilation at rest after STZ treatment. Peripheral chemoreflex responses were significantly blunted in STZ rats as seen by a reduced respiratory rate and minute ventilation to hypoxia. Central chemoreflex responses to hypercapnia, on the other hand, only decreased in respiratory rate following STZ treatment. Overall, our results show that ICV-STZ induces respiratory dysfunction at rest and in response to hypoxia. This provides a new tool to study the underlying mechanisms of breathing disorders in clinical AD.

  2. Antioxidant effect of Aloe vera gel extract in streptozotocin-induced diabetes in rats.

    PubMed

    Rajasekaran, Subbiah; Sivagnanam, Karuran; Subramanian, Sorimuthu

    2005-01-01

    In the present study, an attempt has been made to evaluate the presence of antioxidant property in the alcoholic extract of Aloe vera leaf gel. Oral administration of Aloe vera gel extract at a concentration of 300 mg/kg to diabetic rats significantly decreased the levels of blood glucose, glycosylated hemoglobin and increased hemoglobin. The increased levels of lipid peroxidation and hydroperoxides in tissues of diabetic rats were reverted back to near normal levels after the treatment with gel extract. The extract treatment also resulted in a significant increase in reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the liver and kidney of diabetic rats. These results clearly show the antioxidant property of Aloe vera gel extract. The extract was also more effective than glibenclamide in restoring the values of these parameters.

  3. The effects of photobiomodulation on healing of bone defects in streptozotocin induced diabetic rats

    NASA Astrophysics Data System (ADS)

    Martinez Costa Lino, Maíra D.; Bastos de Carvalho, Fabíola; Ferreira Moraes, Michel; Augusto Cardoso, José; Pinheiro, Antônio L. B.; Maria Pedreira Ramalho, Luciana

    2011-03-01

    Previous studies have shown positive effects of Low level laser therapy (LLLT) on the repair of bone defects, but there are only a few that associates bone healing in the presence of a metabolic disorder as Diabetes Melitus and LLLT. The aim of this study was to assess histologically the effect of LLLT (AsGaAl), 780nm, 70mW, CW, Ø~0.4mm, 16J/cm2 per session) on the repair of surgical defects created in the femur of diabetic and non-diabetic Wistar Albinus rats. Surgical bone defects were created in 60 animals divided into four groups of 15 animals each: Group C (non-diabetic - control); Group CL (non-diabetic + LLLT); Group CD (diabetic); Group CDL (diabetic + LLLT). The animals on the irradiated group received 16 J/cm2 per session divided into four points around the defect, being the first irradiation immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals, (diabetic and non-diabetic) compared to non irradiated ones. It is concluded that LLLT has a positive biomodulative effect on the healing process of bone defects, even when diabetes mellitus was present.

  4. B-1 cells produce insulin and abrogate experimental streptozotocin-induced diabetes.

    PubMed

    Alvares-Saraiva, Anuska M; Novo, Marília C T; de Oliveira, Vivian Cristina; Maricato, Juliana T; Lopes, José Daniel; Popi, Ana Flavia; Mariano, Mario

    2015-05-01

    The participation of B-1 cells in a murine model of spontaneous diabetes has been recently reported. Here, we describe the role of B-1 cells in streptozotocin (STZ) induced diabetes in mice. We demonstrated that XID (B-1 cell-deficient) mice are more susceptible to STZ treatment than WT mice, as evidenced by their higher blood glucose level in response to STZ. Unexpectedly, the XID mice that were i.p. transferred with purified B-1 cells, either before or after the STZ treatment, did not develop diabetes. These cell transfers provided long-lasting protection for the XID mice against STZ-induced diabetes, suggesting that B-1 cells play an important role in the experimental diabetes pathobiology. We also showed that B-1 cell culture supernatants were able to regulate the blood glucose level of the diabetic XID mice, and we identified insulin-producing cells when B-1 cells were differentiated in B-1 cell-derived phagocyte in vitro. These findings provide a novel role for B-1 cells in metabolic processes, presenting a new mechanism to explain the pathogenesis of diabetes and a possible therapeutical target.

  5. Antioxidant potential of bilirubin-accelerated wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumar, Dhirendra; Kumawat, Sanjay; Gopalakrishnan, Anu; Lingaraju, Madhu C; Gupta, Priyanka; Tandan, Surendra Kumar; Kumar, Dinesh

    2014-10-01

    Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats.

  6. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Kant, Vinay; Kumar, Dinesh; Kumar, Dhirendra; Prasad, Raju; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surender K

    2015-05-01

    Substance P (SP) is known to stimulate angiogenesis, fibroblasts proliferation and expressions of cytokines and growth factors involved in wound healing. However, SP level reduces in dermis in diabetics and, hence, it was hypothesized that exogenously applied SP could be helpful in improving wound healing in diabetic rats. Excision skin wound was created on the back of diabetic rats and rats were divided into three groups i.e. (i) saline-, (ii) gel- and (iii) SP-treated. Normal saline, pluronic gel and SP (10(-6)M) in gel were topically applied once daily for 19days. SP treatment significantly increased the wound closure, levels of interleukin-10, and expressions of vascular endothelial growth factor, transforming growth factor-beta1, heme oxygenase-1 and endothelial nitric oxide synthase, whereas it significantly decreased the expression of tumor necrosis factor-alpha, interleukin-1beta and matrix metalloproteinases-9 in the granulation/healing tissue. The inflammatory cells were present for long time in normal saline-treated group. Histological evaluation revealed better extracellular matrix formation with marked fibroblast proliferation and collagen deposition in SP-treated group. Early epithelial layer formation, increased microvessel density and greater growth associated protein-43 positive nerve fibers were also evidenced in SP-treated group. In conclusion, SP treatment markedly accelerated cutaneous wound healing in diabetic rats.

  7. The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice.

    PubMed

    Nishikori, Yoriko; Shiota, Naotaka; Okunishi, Hideki

    2014-11-01

    Mast cells (MCs) reside in cutaneous tissue, and an increment of MCs is suggested to induce vascular regression in the process of wound healing. To clarify participation of MCs in diabetic cutaneous wound healing, we created an excisional wound on diabetic mice 4 weeks after streptozotocin injections and subsequently investigated the healing processes for 49 days, comparing them with control mice. The rate of wound closure was not markedly different between the diabetic and control mice. In the proliferative phase at days 7 and 14, neovascularization in the wound was weaker in diabetic mice than in control mice. In the remodeling phase at day 21 and afterward, rapid vascular regression occurred in control mice; however, neovascularization was still observed in diabetic mice where the number of vessels in granulation tissues was relatively higher than in control mice. In the remodeling phase of the control mice, MCs within the wound began to increase rapidly and resulted in considerable accumulation, whereas the increment of MCs was delayed in diabetic mice. In addition, the number of fibroblast growth factor (FGF)- or vascular endothelial growth factor (VEGF)-immunopositive hypertrophic fibroblast-like spindle cells and c-Kit-positive/VEGFR2-positive/FcεRIα-negative endothelial progenitor cells (EPCs) were higher in diabetic wounds. In conclusion, neovascularization in the proliferative phase and vascular regression in the remodeling phase were impaired in diabetic mice. The delayed increment of MCs and sustained angiogenic stimuli by fibroblast-like spindle cells and EPCs may inhibit vascular regression in the remodeling phase and impair the wound-healing process in diabetic mice.

  8. Histopathological studies of aortic dissection in streptozotocin-induced diabetic APA hamsters.

    PubMed

    Horiuchi, Keiko; Takatori, Atsushi; Inenaga, Toshiaki; Ohta, Etsuko; Ishii, Yoshiyuki; Kyuwa, Shigeru; Yoshikawa, Yasuhiro

    2005-07-01

    Syrian hamsters of the APA strain (APA hamsters) are known to show continuous diabetes accompanied by its complications, such as glomerulosclerosis and atherosclerosis, following a single injection of streptozotocin (SZ). Recently, we observed Stanford type B aortic dissection in three diabetic APA hamsters and histopathological analysis was performed. The histopathologic observations in the false lumen, such as proliferation of granulation tissues, neointima and pseudoneointima, corresponded to the non-thrombosed type of human aortic dissection, and blood clots of the thrombosed type were similar to the remodeling structures of aortic dissection found in human cases. Thus, this model may be useful for investigating the etiology and pathogenesis of aortic dissection accompanying diabetes mellitus in humans.

  9. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice.

    PubMed

    Sidhu, G S; Mani, H; Gaddipati, J P; Singh, A K; Seth, P; Banaudha, K K; Patnaik, G K; Maheshwari, R K

    1999-01-01

    Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re-epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor-beta1 in curcumin-treated wounds compared to controls. Enhanced transforming growth factor-beta1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.

  10. Antihyperlipidemic effect of a polyherbal mixture in streptozotocin-induced diabetic rats.

    PubMed

    Ghorbani, Ahmad; Shafiee-Nick, Reza; Rakhshandeh, Hassan; Borji, Abasalt

    2013-01-01

    The effects of a polyherbal mixture containing Allium sativum, Cinnamomum zeylanicum, Citrullus colocynthis, Juglans regia, Nigella sativa, Olea europaea, Punica granatum, Salvia officinalis, Teucrium polium, Trigonella foenum, Urtica dioica, and Vaccinium arctostaphylos were tested on biochemical parameters in diabetic rats. The animals were randomized into three groups: (1) normal control, (2) diabetic control, and (3) diabetic rats which received diet containing 15% (w/w) of this mixture for 4 weeks. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg). At the end of experiment, the mixture had no significant effect on serum hepatic enzymes, aspartate aminotransferase, and alanine aminotransferase activities. However, the level of fasting blood glucose, water intake, and urine output in treated group was lower than that in diabetic control rats (P < 0.01). Also, the levels of triglyceride and total cholesterol in polyherbal mixture treated rats were significantly lower than those in diabetic control group (P < 0.05). Our results demonstrated that this polyherbal mixture has beneficial effects on blood glucose and lipid profile and it has the potential to be used as a dietary supplement for the management of diabetes.

  11. Antihyperglycemic Effect of Methanol Extract of Syzygium polyanthum (Wight.) Leaf in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Widyawati, Tri; Yusoff, Nor Adlin; Asmawi, Mohd Zaini; Ahmad, Mariam

    2015-09-14

    Syzygium polyanthum (S. polyanthum), a plant belonging to Myrtaceae, is widely used in Indonesian and Malaysian cuisines. Diabetic patients in Indonesia also commonly use it as a traditional medicine. Hence, this study was conducted to investigate the antihyperglycemic effect of the methanol extract (ME) of S. polyanthum leaf and its possible mechanisms of action. To test for hypoglycemic activity, ME was administered orally to normal male Sprague Dawley rats after a 12-h fast. To further test for antihyperglycemic activity, the same treatment was administered to glucose-loaded (intraperitoneal glucose tolerance test, IPGTT) and streptozotocin (STZ)-induced diabetic rats, respectively. Hypoglycemic test in normal rats did not show significant reduction in blood glucose levels (BGLs) by the extract. Furthermore, IPGTT conducted on glucose-loaded normal rats also did not show significant reduction of BGLs. However, repeated administration of metformin and three doses of ME (250, 500 and 1000 mg/kg) for six days caused significant reduction of fasting BGLs in STZ-induced diabetic rats. The possible mechanisms of action of S. polyanthum antihyperglycemic activity were assessed by measurement of intestinal glucose absorption and glucose uptake by isolated rat abdominal muscle. It was found that the extract not only inhibited glucose absorption from the intestine but also significantly increased glucose uptake in muscle tissue. A preliminary phytochemical qualitative analysis of ME indicated the presence of tannins, glycosides, flavonoids, alkaloids and saponins. Additionally, Gas Chromatography-Mass Spectrometry (GC-MS) analysis detected squalene. In conclusion, S. polyanthum methanol leaf extract exerts its antihyperglycemic effect possibly by inhibiting glucose absorption from the intestine and promoting glucose uptake by the muscles.

  12. Hypoglycaemic effect of Berberis vulgaris L. in normal and streptozotocin-induced diabetic rats

    PubMed Central

    Meliani, Nawel; Dib, Mohamed El Amine; Allali, Hocine; Tabti, Boufeldja

    2011-01-01

    Objective To achieve a primary pharmacological screening contained in the aqueous extract of Berberis vulgaris (B. vulgaris) and to examine the hypoglycaemic effect and biochemical parameters of aqueous and saponins extract on groups of rats rendered diabetic by injection of streptozotocin. Methods The phytochemical tests to detect the presence of different compounds were based on the visual observation of color change or formation of precipitate after the addition of specific reagents. Diabetes was induced in rats by intraperitoneal (i.p.) injection of streptozotocin (STZ) at a dose of 65 mg/kg bw. The fasting blood glucose levels were estimated by glucose oxidase-peroxidase reactive strips (Dextrostix, Bayer Diagnostics). Blood samples were taken by cutting the tip of the tail. Serum cholesterol and serum triglycerides were estimated by enzymatic DHBS colorimetric method. Results Administration of 62.5 and 25.0 mg/kg of saponins and aqueous extract respectively in normal rats group shows a significant hypoglycemic activity (32.33% and 40.17% respectively) during the first week. However, diabetic group treated with saponin extract produced a maximum fall of 73.1% and 76.03% at day 1 and day 21 compared to the diabetics control. Also, blood glucose levels of the diabetic rats treated with aqueous extract showed decrease of 78.79% on the first day and the effect remains roughly constant during 3 week. Both extracts also declined significantly biochemical parameters (20.77%-49.00%). The control in the loss of body weight was observed in treated diabetic rats as compared to diabetic controls. Conclusions These results demonstrated significant antidiabetic effects and showed that serum cholesterol and serum triglycerides levels were decreased, significantly, consequently this plant might be of value in diabetes treatment. PMID:23569815

  13. Antidiabetic effect of alcoholic extract of Caralluma sinaica L. on streptozotocin-induced diabetic rabbits.

    PubMed

    Habibuddin, Mohammed; Daghriri, Hassan Ali; Humaira, Touseef; Al Qahtani, Mohammed Saeed; Hefzi, Ali Al Hasan

    2008-05-08

    People of Asir region of Saudi Arabia chew Caralluma sinaica (CS) to lower glucose level. To establish its utility in diabetes mellitus we have under taken this study. The effect of CS on streptozotocin (STZ)-induced diabetic model as well as effect on oral glucose tolerance test were studied. The extract was shown to have positive test for possessing following chemical constituents like phenolic alkaloids, glycosides, flavonoids, coumarins, steroids and tannins. Administration of CS in different doses (50, 100, 150 and 200mg/kg, p.o.) to normal animals caused significant (P<0.01) decrease in glucose level. Prior administration of either CS (100mg/kg, p.o.) or glibenclamide (GB) (5mg/kg, p.o.) blocked the rise of glucose caused by the streptozotocin. Antidiabetic activity of CS was compared with clinically available drug GB. Administration of CS (100mg/kg, p.o.) to diabetic rabbits for 30 days has been shown to decrease plasma glucose level to almost normal level (P<0.001). Liver and kidney weight expressed as percentage of body weight significantly (P<0.05; P<0.01) increased in diabetic rabbits versus normal control (CNT). CS significantly (P<0.05) reversed the increasing weight of liver caused by STZ but not GB. STZ induced lowering of glycogen content of liver and muscle was reversed by both CS and GB. STZ induced a significant (P<0.001) increase in renal glycogen content this was almost normalized by CS (P<0.001) whereas GB significantly decreased (P<0.002) glycogen content. In oral glucose tolerance test administration of glucose increased plasma glucose level significantly in the diabetic control over the 2-h period. Compared to diabetic control plasma glucose levels in rabbits given CS or GB were significantly lower at all the time points that blood was sampled after oral glucose load. Comparing with the GB treatment blood glucose lowering effect was more pronounced for diabetic rabbits given CS. All these effects could explain the basis for use of this plant extract to manage diabetes mellitus.

  14. Biochemical and Neurotransmitters Changes Associated with Tramadol in Streptozotocin-Induced Diabetes in Rats

    PubMed Central

    Ezzeldin, Essam; Souror, Wafaa A. H.; El-Nahhas, Toqa; Soudi, Abdel Nasser M. M.; Shahat, Abdelaaty A.

    2014-01-01

    The incidence of diabetes is increasing worldwide. Chronic neuropathic pain occurs in approximately 25% of diabetic patients. Tramadol, an atypical analgesic with a unique dual mechanism of action, is used in the management of painful diabetic neuropathy. It acts on monoamine transporters to inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA). The purpose of this study was to evaluate the effects of diabetes on the brain neurotransmitter alterations induced by tramadol in rats, and to study the hepatic and renal toxicities of the drug. Eighty Sprague-Dawley rats were divided randomly into two sets: the normal set and the diabetic set. Diabetes was induced in rats. Tramadol was administered orally once daily for 28 days. The levels of DA, NE, and 5-HT in cerebral cortex, thalamus/hypothalamus, midbrain, and brainstem were evaluated in rats. In addition, the renal toxicity and histopathological effects of the drug were assessed. The induction of diabetes altered neurotransmitter levels. Oral administration of tramadol significantly decreased the neurotransmitter levels. Diabetes significantly altered the effects of tramadol in all brain regions. Tramadol affected function and histology of the liver and kidney. The clinical effects of tramadol in diabetic patients should be stressed. PMID:24971322

  15. Attenuation of erythrocyte membrane oxidative stress by Sesbania grandiflora in streptozotocin-induced diabetic rats.

    PubMed

    Sureka, Chandrabose; Ramesh, Thiyagarajan; Begum, Vavamohaideen Hazeena

    2015-08-01

    The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190-220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications.

  16. Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations

    PubMed Central

    Luippold, Gerd; Bedenik, Jessica; Voigt, Anke; Grempler, Rolf

    2016-01-01

    The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose-lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ-rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1 diabetes. PMID:27253523

  17. Effect of bilirubin on triglyceride synthesis in streptozotocin-induced diabetic nephropathy.

    PubMed

    Xu, Jianwei; Lee, Eun Seong; Baek, Seon Ha; Ahn, Shin-Young; Kim, Sejoong; Na, Ki Young; Chae, Dong-Wan; Chin, Ho Jun

    2014-09-01

    We aimed to elucidate the effect of bilirubin on dyslipidemia and nephropathy in a diabetes mellitus (DM) type I animal model. Sprague-Dawley rats were separated into control, DM, and bilirubin-treated DM (Bil) groups. The Bil group was injected intraperitoneally with 60 mg/kg bilirubin 3 times per week and hepatoma cells were cultured with bilirubin at a concentration of 0.3 mg/dL. The Bil group showed lower serum creatinine levels 5 weeks after diabetes onset. Bilirubin treatment also decreased the amount of mesangial matrix, lowered the expression of renal collagen IV and transforming growth factor (TGF)-β1, and reduced the level of apoptosis in the kidney, compared to the DM group. These changes were accompanied by decreased tissue levels of hydrogen superoxide and NADPH oxidase subunit proteins. Bilirubin decreased serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), free fatty acids, and triglycerides (TGs), as well as the TG content in the liver tissues. Bilirubin suppressed protein expression of LXRα, SREBP-1, SCD-1, and FAS, factors involved in TG synthesis that were elevated in the livers of DM rats and hepatoma cells under high-glucose conditions. In conclusion, bilirubin attenuates renal dysfunction and dyslipidemia in diabetes by suppressing LXRα and SREBP-1 expression and oxidative stress.

  18. Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes

    SciTech Connect

    Lohr, J.; Mazurchuk, R.J.; Acara, M.A.; Nickerson, P.A.; Fiel, R.J. )

    1991-01-01

    Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.

  19. Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation

    PubMed Central

    Kesavan, Suresh K.; Bhat, Shweta; Golegaonkar, Sandeep B.; Jagadeeshaprasad, Mashanipalya G.; Deshmukh, Arati B.; Patil, Harshal S.; Bhosale, Santosh D.; Shaikh, Mahemud L.; Thulasiram, Hirekodathakallu V.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.

    2013-01-01

    The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) indu