Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to evaluate the possible protective effects of Nigella sativa L. (NS) against beta-cell damage from streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. NS (0.2 ml/kg/day, i.p.) was injected for 3 days prior to STZ administration, and these injections were continued throughout the 4-week study. Oxidative stress is believed to play a role in the pathogenesis of diabetes mellitus (DM). To assess changes in the cellular antioxidant defense system, we measured the activities of antioxidant enzymes (such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT)) in pancreatic homogenates. We also measured serum nitric oxide (NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, to determine whether there is an imbalance between oxidant and antioxidant status. Pancreatic beta-cells were examined by immunohistochemical methods. STZ induced a significant increase in lipid peroxidation and serum NO concentrations, and decreased antioxidant enzyme activity. NS treatment has been shown to provide a protective effect by decreasing lipid peroxidation and serum NO, and increasing antioxidant enzyme activity. Islet cell degeneration and weak insulin immunohistochemical staining was observed in rats with STZ-induced diabetes. Increased intensity of staining for insulin, and preservation of beta-cell numbers were apparent in the NS-treated diabetic rats. These findings suggest that NS treatment exerts a therapeutic protective effect in diabetes by decreasing oxidative stress and preserving pancreatic beta-cell integrity. Consequently, NS may be clinically useful for protecting beta-cells against oxidative stress.
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PMID:Effects of Nigella sativa on oxidative stress and beta-cell damage in streptozotocin-induced diabetic rats. 1522 10

The aim of the present study was the evaluation of possible protective effects of exercise against beta-cell damage in streptozotocin (STZ)-induced diabetes in rats. The animals were divided into five groups: the control group, the STZ-induced diabetes group, the STZ-induced diabetes and light-intensity exercise group, the STZ-induced diabetes and moderate-intensity exercise group, and the STZ-induced diabetes and heavy-intensity exercise group. Animals in the exercise groups were made to swim one of three exercise protocols once a day for 12 consecutive weeks. STZ was injected intraperitoneally at a single dose of 50 mg/kg for diabetes induction. Exercise training was continued for 4 weeks prior to STZ administration; these applications were continued end of the study (for 12 weeks). Erythrocyte and pancreatic tissue malondialdehyde (MDA) levels and serum nitric oxide (NO) concentration were measured. Moreover glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) were also measured in pancreatic homogenates. Pancreatic beta-cells were examined by immunohistochemical methods. STZ increased lipid peroxidation and decreased the antioxidant enzyme activity significantly. Exercise, especially moderate-intensity exercise has shown protective effect probably through decreasing lipid peroxidation and increasing antioxidant enzyme activity. Islet cell degeneration and weak insulin immunohistochemical staining were observed in STZ induced diabetic rats. Increased intensity of staining for insulin and preservation of beta-cell numbers were apparent in the exercise-applied diabetic rats. Interestingly, the best result was obtained from moderate-intensity exercise. These findings suggest that exercise has a therapeutic and/or protective effect in diabetes by decreasing oxidative stress and preservation of pancreatic beta-cell integrity.
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PMID:Exercise training prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas. 1524 Sep 23

Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. To evaluate the effects on IAP of vitamin E administration in adolescents with type 1 diabetes and early signs of microangiopathy, 12 adolescents (aged 11-21 y; diabetes duration 10-18) were studied. Eight had retinopathy [background (four), preproliferative (three), or proliferative (one)], four had persistent microalbuminuria, and seven had both. Skin fibroblasts were obtained by biopsies and cultured in Dulbecco's modified Eagle's medium. CuZn superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione-peroxidase (GPX) activity and mRNA expression were measured before and after 3 mo of synthetic vitamin E supplementation (600 mg twice daily); on both occasions, IAP was evaluated at different ex vivo glucose concentrations (5 and 22 mM). Ten adolescents with type 1 diabetes (aged 12-20 y) without angiopathy and eight healthy volunteers (aged 15-22 y) participated as control subjects. Vitamin E serum levels were measured throughout the study. In normal glucose concentrations, CuZnSOD, MnSOD, CAT, and GPX activity and mRNA expression were not different among the groups. In high glucose, CuZnSOD activity and mRNA increased similarly in all groups [angiopathics: 0.96 +/- 0.30 U/mg protein; 9.9 +/- 3.2 mRNA/glyceraldehyde-3-phosphate dehydrogenase). CAT and GPX activity and mRNA did not increase in high glucose only in adolescents with angiopathy (0.35 +/- 0.09; 4.2 +/- 0.1 and 0.52 +/- 0.14; 2.4 +/- 0.9, respectively). MnSOD did not change in any group. Vitamin E supplementation had no effect on any enzymatic activity and mRNA in both normal and hyperglycemic conditions. Adolescents with early signs of diabetic angiopathy have defective IAP and activity, which are not modified by vitamin E.
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PMID:Effects of vitamin E supplementation on intracellular antioxidant enzyme production in adolescents with type 1 diabetes and early microangiopathy. 1534 73

Oxidative stress is produced under diabetic conditions and is likely involved in progression of pancreatic beta-cell dysfunction found in diabetes. Possibly due to low levels of antioxidant enzyme expressions, beta-cells are vulnerable to oxidative stress. When beta-cell-derived cell lines or isolated rat islets were exposed to oxidative stress, insulin gene expression was markedly decreased. Furthermore, when diabetic C57BL/ KsJ-db/db mice were treated with antioxidants, glucose tolerance was ameliorated. Histological analyses of the pancreata revealed that the beta-cell mass is significantly larger in the mice treated with the antioxidants. The antioxidant treatment also preserved the amounts of insulin content and insulin mRNA. As a possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (PDX-1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. Furthermore, oxidative stress induces nucleocytoplasmic translocation of PDX-1 through activation of the c-Jun N-terminal kinase (JNK) pathway, which leads to suppression of insulin gene expression. Taken together, oxidative stress and consequent activation of the JNK pathway are involved in progression of beta-cell dysfunction found in diabetes, and thus are a therapeutic target for diabetes.
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PMID:Oxidative stress and the JNK pathway as a potential therapeutic target for diabetes. 1551 4

Oxygen free radicals have been suggested to be a contributory factor in diabetes complications. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the heart tissue of diabetic rats. We investigated the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in the hearts of both control and streptozotocin-induced diabetic rats. In the heart of diabetic rats, the activity of total superoxide dismutase decreased significantly (p < 0.005), whereas the activity of catalase and glutathione peroxidase increased to a large extent (p < 0.0001 and p = 0.05, respectively) at the end of the fourth week compared with the control group. Glyburide treatment of diabetic rats for 4 weeks corrected the changes observed in diabetic heart. In addition, blood glucose levels of untreated diabetic rats decreased following the glyburide treatment. These results demonstrate that the sulfonylurea glyburide is capable of exerting direct insulin-like effect on heart superoxide dismutase, catalase and glutathione peroxidase activities of diabetic rats in vivo.
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PMID:The effects of the sulfonylurea glyburide on glutathione peroxidase, superoxide dismutase and catalase activities in the heart tissue of streptozotocin-induced diabetic rat. 1553 41

In the present study, we investigated the effects of simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, on lipid metabolism, lipid peroxidation, antioxidant enzyme activities and ultrastructure of diabetic rat lung. Diabetes was induced by a single injection of streptozotocin (45 mg kg(-1), i.p.). After 8 weeks induction of diabetes, some control and diabetic rats were treated with simvastatin (10 mg kg(-1) rat day(-1); orally) for 4 weeks. Diabetes resulted in significantly high levels of blood glucose and plasma lipids. Malondialdehyde levels were unchanged after 12-week-old diabetic rats, whereas catalase activity significantly decreased in the lung. Glutathione peroxidase activity and nitric oxide level were significantly elevated in the diabetic lung. Histological analysis of the diabetic lung revealed some deterioration in the structure. Simvastatin treatment reduced plasma lipid levels and partially decreased the severity of hyperglycaemia. Catalase, glutathione peroxidase activities and nitric oxide levels were partially restored and accompanied by improved structure in diabetic lung by the simvastatin treatment. These results suggest that structural disturbances and alteration of antioxidative enzyme activities occurred in diabetic lung. Simvastatin treatment may provide some benefits in the maintenance of antioxidant status and structural organization of diabetes-induced injury of lung.
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PMID:Effects of simvastatin treatment on oxidant/antioxidant state and ultrastructure of streptozotocin-diabetic rat lung. 1554 Feb 54

The effect of various doses (0, 10, 20, 40, or 80 mg/kg body weight) of naringin (a citrus flavonone) was studied on streptozotocin (STZ)-induced hyperglycaemic rats to evaluate the possible hypoglycaemic and antioxidant activity of naringin in diabetes. In comparison to the normoglycaemic group the treatment of rats with a single dose of STZ (65 mg/kg body weight) only revealed a significant increase (P < 0.05) in plasma hydrogen peroxide (H2O2) by 230%, increased the thiobarbituric acid reactive substances (TBARS) as index of the lipid peroxidation level by 69%, while total antioxidant activity was decreased by 36%, with a consistent significant decrease (P < 0.05) in the activity of erythrocytes antioxidative enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and paraoxonase (PON). Exogenous administration of individual gradual doses of naringin to hyperglycaemic rats causes a dose-dependent decrease of the glucose level, an increase of the insulin concentration, a decrease of the H2O2 and TBARS levels, as well as the increase of the total antioxidant status with an increase of antioxidant enzyme activities (CAT, SOD, GPx, and PON). From this study, it may be concluded that all doses of naringin provided a significant amelioration of hypoglycaemic and antioxidant activity in STZ-induced diabetic rats, however, the greatest effect of naringin was observed at 80 mg/kg body weight.
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PMID:The influence of naringin on the oxidative state of rats with streptozotocin-induced acute hyperglycaemia. 1554 Jun 7

The aim of the present study was the evaluation of possible protective effects of quercetin (QE) against beta-cell damage in experimental streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg kg(-1) for diabetes induction. QE (15 mg kg(-1) day, intraperitoneal (i.p.) injection) was injected for 3 days prior to STZ administration; these injections were continued to the end of the study (for 4 weeks). It has been believed that oxidative stress plays a role in the pathogenesis of diabetes mellitus (DM). In order to determine the changes of cellular antioxidant defense system, antioxidant enzymes such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in pancreatic homogenates. Moreover we also measured serum nitric oxide (NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, if there is an imbalance between oxidant and antioxidant status. Pancreatic beta-cells were examined by immunohistochemical methods. STZ induced a significant increase lipid peroxidation, serum NO concentrations and decreased the antioxidant enzyme activity. Erythrocyte MDA, serum NO and pancreatic tissue MDA significantly increased (P < 0.05) and also the antioxidant levels significantly decreased (P < 0.05) in diabetic group. QE treatment significantly decreased the elevated MDA and NO (P < 0.05), and also increased the antioxidant enzyme activities (P < 0.05). QE treatment has shown protective effect possibly through decreasing lipid peroxidation, NO production and increasing antioxidant enzyme activity. Islet cells degeneration and weak insulin immunohistochemical staining was observed in STZ induced diabetic rats. Increased staining of insulin and preservation of islet cells were apparent in the QE-treated diabetic rats. These findings suggest that QE treatment has protective effect in diabetes by decreasing oxidative stress and preservation of pancreatic beta-cell integrity.
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PMID:Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas. 1562 56

Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which humans are exposed in a variety of environment situations and is also a product of lipid peroxidation. Increased unsaturated aldehyde levels and reduced antioxidant status play an important role in the pathogenesis of a number of human diseases such as Alzheimer's, atherosclerosis, and diabetes. Mammalian thioredoxin reductase (TR), a central antioxidant enzyme, is a selenoprotein that catalyzes the reduction of oxidized thioredoxin. The findings reported here show that low concentrations of acrolein rapidly inactivate TR, both in vitro and in vivo. These data suggest that acrolein may directly inactivate TR, resulting in an increase in oxidative cellular damage. In addition, we also found that the initial inactivation of TR molecules by acrolein triggers a compensatory signal for inducing TR gene expression in human umbilical vein endothelial cells (HUVEC). The results of the present study suggest that HUVEC may have a protective system against cell damage by acrolein via the upregulation of TR, which is an adaptive response to oxidative stress.
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PMID:Induction of thioredoxin reductase as an adaptive response to acrolein in human umbilical vein endothelial cells. 1565 4

Diabetes mellitus is characterized by hyperglycemia and, in chronic disease, by microvascular pathologies, especially in the kidney, peripheral nerve, and eye. Although hyperglycemia can be controlled with insulin and/or antihyperglycemic medications, diabetic retinopathy continues to be the leading cause of blindness in the United States. Because increased oxidative stress may be a cause of retinopathy, this study examined the hypothesis that administration of exogenous antioxidants can restore a more balanced oxidative condition. Normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats received daily intraperitoneal doses (10 mg/kg) of beta-carotene, alpha-lipoic, and Pycnogenol individually or in combinations for 14 days, after which retinae were dissected and fractionated for the assay of activities of glutathione reductase, glutathione peroxidase, gamma-glutamyl transferase, and superoxide dismutase. In normal rats, treatment with antioxidant combinations led to a decrease in gamma-glutamyl transferase activity; beta-carotene plus pycnogenol treatment decreased the activity of both glutathione-related enzymes. Decreased retinal gamma-glutamyl transferase activity of diabetic rats was normalized by the administration of pycnogenol alone or in combination with beta-carotene. In diabetic rats, retinal glutathione reductase activity increased after treatment with beta-carotene alone or with pycnogenol. Treatment with pycnogenol and alpha-lipoic acid alone or in combination decreased the activity of glutathione peroxidase, while this activity was increased after treatment with a combination of all antioxidants. Elevated activity of superoxide dismutase in diabetic retina was normalized by treatment with alpha-lipoic acid and with pycnogenol and beta-carotene in combination, but not with all three together. Antioxidants can access the retina and, once there, can alter antioxidant enzyme activities. In both normal and diabetic rats, combinations of antioxidants have different effects on retinal antioxidant enzyme activities than do individual antioxidants.
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PMID:Effects of antioxidant treatment on normal and diabetic rat retinal enzyme activities. 1571 25


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