Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GH and IGF-I concentrations decline with age. Age-related changes appear to be linked to decreases in the anabolic hormones, GH and IGF-I. The aim of this study was to investigate the antioxidant, anabolic, and metabolic effects of the IGF-I replacement therapy, at low doses, in aging rats. Three experimental groups were included in this protocol: young healthy controls (17 wk old); untreated old (O) rats (103 wk old); and aging rats (103 wk old) treated with IGF-I during 1 month (2.25 microg IGF-I/100 g body weight(-1).d(-1)). Compared with young controls, untreated aging rats showed a reduction of IGF-I and testosterone levels, and a decrease of serum total antioxidant status, which were corrected by IGF-I therapy. In addition, untreated O presented increased levels of serum glucose with hyperinsulinemia, cholesterol, and triglycerides, and a reduction of free fatty acid concentrations. IGF-I therapy was able to revert insulin resistance, and to reduce cholesterol and triglycerides levels increasing significantly free fatty acid concentrations. The O group showed higher oxidative damage in brain and liver tissues associated with alterations in antioxidant enzyme activities. IGF-I therapy reduced oxidative damage in brain and liver, normalizing antioxidant enzyme activities and mitochondrial dysfunction. In conclusion, low doses of IGF-I restore circulating IGF-I, improve glucose and lipid metabolism, increase testosterone levels and serum total antioxidant capability, and reduce oxidative damage in brain and liver associated with a normalization of antioxidant enzyme activities and mitochondrial function.
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PMID:Low doses of insulin-like growth factor I improve insulin resistance, lipid metabolism, and oxidative damage in aging rats. 1818 55

Serum IGF-I levels decline with age. We have recently reported that in aging rats the exogenous administration of IGF-I restores IGF-I circulating levels and age related-changes, improving glucose and lipid metabolisms, increasing testosterone levels and serum total antioxidant capability, and reducing oxidative damage in the brain and liver associated with a normalization of antioxidant enzyme activities. Understanding that mitochondria are one of the most important cellular targets of IGF-I, the aims of this study were to characterize mitochondrial dysfunction and study the effect of IGF-I therapy on mitochondria, leading to cellular protection in the following experimental groups: young controls, untreated old rats, and aging rats treated with IGF-I. Compared with young controls, untreated aging rats showed an increase of oxidative damage in isolated mitochondria with a mitochondrial dysfunction characterized by: depletion of membrane potential with increased proton leak rates and intramitochondrial free radical production, and a significant reduction of ATPase and complex IV activities. In addition, mitochondrial respiration from untreated aging rats was atractyloside insensitive, suggesting that the adenine nucleotide translocator was uncoupled. The adenine nucleotide translocator has been shown to be one of the most sensitive locations for pore opening. Accordingly, untreated aging rats showed a significant overexpression of the active fragment of caspases 3 and 9. IGF-I therapy corrected these parameters of mitochondrial dysfunction and reduced caspase activation. In conclusion, these results show that the cytoprotective effect of IGF-I is closely related to a mitochondrial protection, leading to reduce free radical production, oxidative damage, and apoptosis, and to increased ATP production.
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PMID:Low doses of insulin-like growth factor-I induce mitochondrial protection in aging rats. 1827 48

We investigated the effect of curcumin on insulin resistance and glucose homeostasis in male C57BL/KsJ-db/db mice and their age-matched lean non-diabetic db/+ mice. Both db/+ and db/db mice were fed with or without curcumin (0.02%, wt/wt) for 6 wks. Curcumin significantly lowered blood glucose and HbA 1c levels, and it suppressed body weight loss in db/db mice. Curcumin improved homeostasis model assessment of insulin resistance and glucose tolerance, and elevated the plasma insulin level in db/db mice. Hepatic glucokinase activity was significantly higher in the curcumin-supplemented db/db group than in the db/db group, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly lower. In db/db mice, curcumin significantly lowered the hepatic activities of fatty acid synthase, beta-oxidation, 3-hydroxy-3-methylglutaryl coenzyme reductase, and acyl-CoA: cholesterol acyltransferase. Curcumin significantly lowered plasma free fatty acid, cholesterol, and triglyceride concentrations and increased the hepatic glycogen and skeletal muscle lipoprotein lipase in db/db mice. Curcumin normalized erythrocyte and hepatic antioxidant enzyme activities (superoxide dismutase, catalase, gluthathione peroxidase) in db/db mice that resulted in a significant reduction in lipid peroxidation. However, curcumin showed no effect on the blood glucose, plasma insulin, and glucose regulating enzyme activities in db/+ mice. These results suggest that curcumin seemed to be a potential glucose-lowering agent and antioxidant in type 2 diabetic db/db mice, but had no affect in non-diabetic db/+ mice.
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PMID:Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. 1839 69

Hyperglycemia, abnormal lipid and antioxidant profiles are the most usual complications in diabetes mellitus. In the present study, the antihyperglycemic, antihyperlipemic and antioxidant potency of an ethanol extract of Costus speciosus root was investigated in alloxan-induced diabetic male (Charles Foster) rats. Four groups of alloxan diabetic rats (n = 6) were administered orally with different doses of Costus speciosus root extract (150, 300 and 450 mg/kg BW) and a standard drug, glibenclamide (600 microg/kg BW), for 4 weeks. Two groups of rats (n = 6) served as normal and diabetic controls. While the diabetic controls showed significant abnormal carbohydrate, lipid and antioxidant profiles, administration of 150 mg/kg BW dose neither improved glucose nor lipid metabolism and antioxidant levels. Administration of 300 and 450 mg/kg BW doses, however, resulted in a reversal of diabetes and its complications. Both doses significantly brought down blood glucose concentration (26.76%, 34.68%), increased glycogenesis and decreased glyconeogenesis bringing the glucose metabolism toward normalcy. These doses also reversed the hyperlipidemia by reducing plasma total lipid (12.87%, 178.24%), cholesterol (21.92%, 30.77%) and triglyceride (25.32%, 33.99%) and improved hepatic antioxidant enzyme activities. The high dose (450 mg/kg BW) was found to have more potential antioxidant activities compared with glibenclamide. It is concluded that Costus speciosus root extract possesses anti-hyperglycemic, antihyperlipemic and antioxidative effects, which may prove to be of clinical importance in the management of diabetes and its complications.
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PMID:Antihyperglycemic and hypolipidemic effects of Costus speciosus in alloxan induced diabetic rats. 1844 47

It has recently been estimated by the American Diabetes Association that 21 million Americans, or about 7% of the U.S. population, have diabetes, while an additional 54 million Americans have pre-diabetes. The onset and progression of these disorders and related complications are linked to impairments in glucose and lipid metabolism, both of which are associated with increased production of reactive oxygen and nitrogen species (RONS). Increased RONS production coupled with impaired antioxidant defense (a common finding among patients with diabetes) promotes oxidation of specific biomolecules (lipid, protein, DNA), which can lead to an exacerbation of diabetic complications. While bloodborne variables related to these disorders have traditionally been measured in a fasted state, increasing evidence suggests that measurement of postprandial glycemia, lipemia, and oxidative stress may provide more important clinical information concerning an individual's susceptibility to diabetes onset and disease progression. While drugs to treat hyperglycemia and hyperlipidemia have been reported in some studies to promote favorable outcomes related to attenuating the postprandial rise in blood glucose and triglycerides, one non-pharmaceutical approach which may have promise is the performance of regular exercise. Both acute and chronic exercise may aid in attenuating postprandial oxidative stress in three distinct ways. First, exercise stimulates an increase in endogenous antioxidant enzyme activity. Second, exercise improves blood glucose clearance via enhanced GLUT 4 translocation and protein content, as well as enhanced insulin-insulin receptor binding and post-receptor signaling. Third, exercise improves blood triglyceride clearance via a reduced chylomicron-triglyceride half-life and enhanced lipoprotein lipase activity. In this article we provide evidence for the potential role of exercise in modulating postprandial oxidative stress in diabetic and pre-diabetic individuals. It is certainly possible that exercise may prove beneficial in this regard. If so, and in accordance with the recent joint initiative of the American College of Sports Medicine and the American Medical Association, exercise may be viewed as "medicine" for individuals who are at increased risk for postprandial oxidative stress.
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PMID:Can exercise minimize postprandial oxidative stress in patients with type 2 diabetes? 1899 99

Elevated blood glucose is a key initiator of mechanisms leading to diabetic neuropathy. Increases in glucose induce acute mitochondrial oxidative stress in dorsal root ganglion (DRG) neurons, the sensory neurons normally affected in diabetic neuropathy, whereas Schwann cells are largely unaffected. We propose that activation of an antioxidant response in DRG neurons would prevent glucose-induced injury. In this study, mild oxidative stress (1 microM H2O2) leads to the activation of the transcription factor Nrf2 and expression of antioxidant (phase II) enzymes. DRG neurons are thus protected from subsequent hyperglycemia-induced injury, as determined by activation of caspase 3 and the TUNEL assay. Schwann cells display high basal antioxidant enzyme expression and respond to hyperglycemia and mild oxidative stress via further increases in these enzymes. The botanical compounds resveratrol and sulforaphane activate the antioxidant response in DRG neurons. Other drugs that protect DRG neurons and block mitochondrial superoxide, identified in a compound screen, have differential ability to activate the antioxidant response. Multiple cellular targets exist for the prevention of hyperglycemic oxidative stress in DRG neurons, and these form the basis for new therapeutic strategies against diabetic neuropathy.
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PMID:Sensory neurons and schwann cells respond to oxidative stress by increasing antioxidant defense mechanisms. 1907 99

The improvement of diabetic complications such as lipid lowering and anti-oxidative potential of Hydrangea Dulcis Folium (HDF) was studied in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into 3 groups after induction of streptozotocin (STZ)-diabetes: normal control; diabetic control; diabetic-HDF supplement (hot water extract 40 g/kg diet); and fed experimental diets for 3 weeks. Serum glucose and insulin concentrations, serum lipid profile, intraperitoneal glucose tolerance test, and liver cytosolic antioxidant enzyme levels were measured. The HDF supplement significantly decreased serum glucose concentration, increased insulin level, and improved glucose homeostasis in diabetic control rats. The total cholesterol and triglyceride concentrations in the serum and liver were markedly reduced by HDF treatment in STZ-diabetic rats. Moreover, low density lipoprotein (LDL)-, VLDL-, and high density lipoprotein (HDL)-cholesterol levels were ameliorated in HDF supplemented diabetic rats. Decreased fecal excretions of cholesterol, triglyceride, and bile acid in diabetic rats were significantly increased by HDF consumption. HDF supplement reversed the effects of the oxidative stress system of liver in diabetic rats. Lipid peroxidation of diabetic rats, assessed by thiobarbituric acid reactive substance (TBARS), as well as superoxide dismutase (SOD) activities were significantly increased, and glutathione contents were decreased in diabetic rats. HDF supplement reverted these parameters to near normal value. Our data suggest that HDF supplement could be used to improve the glucose and lipid metabolism as well as to reduce the imbalance between the generation of reactive oxygen species (ROS) and the scavenging enzyme activity in preventing diabetic complications.
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PMID:Improvement of diabetic complication by hydrangea dulcis folium in streptozotocin-induced diabetic rats. 1912

SMND-309, a novel compound (2E)-2-[6-[(E)-2-carboxyvinyl]-2,3-dihydroxyphenyl]-3-(3,4-dihydroxyphenyl) acrylic acid, is a new derivate of salvianolic acid B. The present study elucidates the effects of SMND-309 on the cultured rat cortical neuron damage induced by oxygen-glucose deprivation. The results show that SMND-309 treatment obviously attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons by increasing cell survival rate, mitochondrial antioxidant enzyme activities, mitochondrial respiratory enzymes activities, mitochondrial respiratory control ratio and the adenosine triphosphate content, and by decreasing mitochondrial malondialdehyde content, lactate dehydrogenase release, intracellular Ca(2+) level and caspase-3 activity in a concentration-dependent manner. Moreover, SMND-309 exhibits significantly higher potency as compared to salvianolic acid B. These findings indicate that SMND-309 has a protective potential against cerebral ischaemic injury and its protective effects may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvement of mitochondrial energy metabolism and antioxidant property.
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PMID:SMND-309, a novel derivate of salvianolic acid B, attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons. 1914 49

The effects of various doses of lycopene were studied in streptozotocin (STZ)-induced hyperglycaemic rats to evaluate its possible hypoglycaemic, hypolipidaemic and antioxidant activity in diabetes. Compared to the normoglycaemic group, the treatment of rats with a single dose of STZ (65 mg/kg body weight) revealed a significant increase (p<0.05) only in plasma hydrogen peroxide (H(2)O(2)), i.e. by 230%; it 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 consistently significant decrease (p<0.05) in the activity of erythrocytes antioxidative enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). The levels of total lipid, triglycerides and total cholesterol in serum of hyperglycaemic rats were increased by 14%, 65% and 36%, respectively, while HDL-C decreased by 22% compared to the normoglycaemic group. Exogenous administration of individual gradual doses of lycopene to hyperglycaemic rats causes a dose-dependent decrease in glucose level, an increase of insulin concentration, a decrease of H(2)O(2) and TBARS levels, as well as increased total antioxidant status with increased antioxidant enzyme activities (CAT, SOD and GPx) with improvement in serum lipid profile. It is obvious from this study that lycopene acts as an antidiabetic agent through lowering the free radical and has an improving effect on serum that reaches the normal level; the greatest effect of lycopene was observed at 90 mg/kg body weight.
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PMID:Amelioration of streptozotocin-induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene. 1914 34

Oxidative stress mediated by hyperglycaemia-induced generation of reactive oxygen species (ROS) contributes significantly to the development and progression of diabetes and related vascular complications. NAD(P)H oxidase has been implicated as the major source of ROS generation in the vasculature in response to high glucose and advanced glycation end-products. Sustained activation of NAD(P)H oxidase in diabetes may diminish intracellular levels of NADPH, an essential cofactor for endothelial NO synthase (eNOS) and several antioxidant systems. Recent evidence suggests that basal ROS production via NAD(P)H oxidase may upregulate antioxidant enzyme defenses via redox signalling. Thus, NAD(P)H oxidase may serve as a double-edged sword, with transient activation providing a feedback defense against excessive ROS generation through the activation of receptor tyrosine kinases and the redox-sensitive Nrf2-Keap1 signalling pathway. Overproduction of ROS leads to eNOS uncoupling, mitochondrial dysfunction, and impaired antioxidant defenses owing to depletion of intracellular NADPH. Given the largely negative outcome of antioxidant therapy in the treatment of diabetic complications, targeting the redox-sensitive transcription factor Nfr2 may provide an effective strategy to restore antioxidant defenses in diabetes.
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PMID:Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling. 1917 52


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