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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to evaluate diabetic nephropathy by determining markers of oxidative stress and the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), albumin and to investigate the possible protective effects of in vivo melatonin on renal tubular oxidative damage in diabetic rats. 2. Twenty-six rats were randomly divided into three groups: (i) group I, control, non-diabetic rats (n = 9); (ii) group II, untreated diabetic rats (n = 8); and (iii) group III, melatonin-treated diabetic rats (n = 9). In groups II and III, diabetes developed 3 days after administration of a single dose of streptozotocin (35 mg/kg, i.p.). Thereafter, whereas the rats in group II received no treatment, rats in group III began to receive 10 mg/kg per day, i.p., melatonin for 8 weeks. Malondialdehyde (MDA), an index of lipid peroxidation, NAG and microalbumin in the urine, markers of renal tubular damage, were the parameters used for oxidative stress-induced renal injury. Superoxide dismutase (SOD), xanthine oxidase (XO) and glutathione peroxidase (GSH-Px) activities were determined to evaluate changes in the anti-oxidant status of kidney tissue. 3. In untreated diabetic rats, urinary NAG, albumin and renal MDA levels were markedly increased compared with control rats (P < 0.0001). However, these parameters were reduced in diabetic rats by melatonin treatment (P < 0.0001). Urinary excretion of NAG was positively correlated with the microalbuminuria and renal MDA levels (r = 0.8; P < 0.0001). The SOD and XO activities in the untreated diabetic group were found to be significantly higher than those of the control group (P < 0.0001). Superoxide dismutase and XO activities decreased in melatonin-treated rats compared with untreated diabetic rats (P < 0.002 and P < 0.023, respectively). However, the decrease did reach levels seen in control rats. There were no significant differences in GSH-Px activity between the three groups. 4. Therefore, on the basis of these data, we suggest that urinary NAG, albumin excretion, XO activity and MDA levels are more valuable parameters showing the degree of renal tubular injury than classical markers of oxidative stress, including SOD and GSH-Px, in diabetic rat kidneys. Melatonin has an ameliorating effect on oxidative stress-induced renal tubular damage via its anti-oxidant properties. Thus, it may be suggested that urinary NAG excretion and microalbuminuria may be important markers showing the degree of renal changes and the success of long-term treatment of renal impairment with melatonin.
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PMID:Melatonin reduces urinary excretion of N-acetyl-beta-D-glucosaminidase, albumin and renal oxidative markers in diabetic rats. 1644 6

To test the hypothesis that protein kinase C (PKC)beta-induced reactive oxygen species (ROS) underlie the vascular dysfunction in diabetes, we examined the effects of (S)-13[(dimethylamino)-methyl]-10,11-14,15-tetrahydro-4,9:16,21-dimetheno-1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadi-azacyclohexadecene-1,3(2H)-dione (LY333531; LY), a specific PKCbeta inhibitor, on arachidonic acid (AA)-mediated dilation in small coronary arteries from streptozotocin-induced diabetic rats. This study was designed to determine whether diabetes impairs AA-induced vasodilation of small coronary arteries and whether this defect could be blunted by dietary treatment with LY. Coronary diameter was measured using videomicroscopy in isolated pressurized vessels. In controls, AA dose dependently dilated coronary arteries, with 1 muM producing 54.7 +/- 3.1% and 30 microM producing 72.0 +/- 3.0% dilation (n = 9). In diabetic rats, 1 microM AA only produced 31.4 +/- 3.8% (n = 8; p < 0.01 versus control) and 30 microM 43.8 +/- 3.7% dilation (n = 8; p < 0.001 versus control). Nitroprusside-mediated vasodilations were similar in control and diabetic rats. In contrast, in diabetic rats receiving LY, AA-mediated coronary dilations were normal. In controls, AA-mediated vasodilation was inhibited by miconazole (an inhibitor of cytochrome P450 epoxygenase) and by iberiotoxin (IBTX, an inhibitor of the large conductance Ca(2+)-activated K(+) channel), but miconazole and IBTX had no effects in diabetic vessels. In diabetic rats receiving LY, the effects of miconazole and IBTX were similar to control. Superoxide dismutase restored responses to AA in diabetic vessels but had no effect in vessels from control or diabetic rats on LY. These results suggest that AA-mediated vasodilation in rat coronary arteries are impaired in diabetic rats due to increases in generation of ROS. LY protects against these defects in diabetes through inhibition of PKCbeta-mediated production of ROS.
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PMID:Inhibition of protein kinase Cbeta protects against diabetes-induced impairment in arachidonic acid dilation of small coronary arteries. 1686 98

The effect of sulfur dioxide (SO(2)) on hippocampus antioxidant status, lipid peroxidation and learning and memory was investigated in diabetic rats. A total of 40 rats were divided into four equal groups: Control (C), SO(2) + C (SO(2)), diabetic (DM) and SO(2) + D (DMSO(2)). Experimental diabetes mellitus (DM) was induced by i.v injection of alloxan with a dose of 50 mg/kg body weight. Ten ppm SO(2) was administered to the rats in the sulfur dioxide groups in an exposure chamber. Exposure occurred 1 h/d, 7 d/wk, for 6 wk; control rats were exposed to filtered air during the same time periods. SO(2) exposure, while markedly increasing Cu-Zn Superoxide dismutase activity, significantly decreased glutathione peroxidase activity in diabetic and non-diabetic groups compared with the C group; hippocampus catalase activity was unaltered. Hippocampus thiobarbituric acid reactive substances (TBARS) were found to be elevated in all experimental groups with respect to control group. The active avoidance training results indicated that diabetic condition has been associated with learning and memory impairment. SO(2) exposure caused deficits of learning and memory. Diabetes mellitus-induced impairment of learning and memory were potentiated by SO(2) exposure. These findings suggest that exposure to SO(2) by increasing lipid peroxidation, can change antioxidant enzyme activities and can elevated intensity of deficits of learning and memory in diabetic rats.
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PMID:Effect of sulfur dioxide on active and passive avoidance in experimental diabetes mellitus: relation to oxidant stress and antioxidant enzymes. 1761 16

Interactions of free radicals such as superoxide (O2-), nitric oxide (NO), and peroxynitrite (ONOO-) are important in pathophysiological conditions such as hypertension, atherosclerosis, diabetes and the resulting cardiovascular diseases. Excessive levels of superoxide during oxidative stress cause a reduction in NO bioavailability by forming peroxynitrite and resulting in endothelial dysfunction. Superoxide dismutase (SOD) competes with NO for superoxide, and reduces the formation of peroxynitrite. In this study, we developed a mathematical model for free radical transport within and around an arteriolar vessel based on the fundamental principles of mass balance, reaction kinetics, and vascular geometry. We used the model to study the effect of the three types of SOD, viz. CuZn-SOD, Mn-SOD and extra cellular-SOD, on the bioavailability of NO. Results indicate that SOD location and concentration in the arteriole significantly affect superoxide concentration. The model predicts that a reduction in SOD levels results in increased superoxide and peroxynitrite concentrations and decreased NO concentration in the vessel. The results also suggest a role of SOD in the amelioration of oxidative stress and NO bioavailability in microcirculation. This model will help in furthering our knowledge of endothelial dysfunction in pathological conditions and the impact of specific SODs on free radical interactions.
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PMID:Impact of superoxide dismutase on nitric oxide and peroxynitrite levels in the microcirculation--a computational model. 1800 34

Beyond our inherited genetic make-up environmental factors are central for health and disease and finally determine our life span. Amongst the environmental factors nutrition plays a prominent role in affecting a variety of degenerative processes that are linked to aging. The exponential increase of non-insulin-dependent diabetes mellitus in industrialized nations as a consequence of a long-lasting caloric supernutrition is an expression of this environmental challenge that also affects aging processes. The most consistent effects along the environmental factors that slow down aging - from simple organisms to rodents and primates - have been observed for caloric restriction. In the yeast Saccharomyces cerevisiae, the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, sirtuins (silencing information regulators) have been identified to mediate as "molecular sensors" the effects of caloric restriction on aging processes. Sirtuins are NAD(+)-dependent deacetylases that are activated when e.g. cell energy status is low and the NAD(+) over NADH ratio is high. As a consequence transcription rates of a variety of genes including that of the apoptosis inducing p(53) gene are reduced. Moreover, in C. elegans, sirtuins were shown to interact with proteins of the insulin/IGF-1 signaling cascade of which several members are known to extend life span of the nematodes when mutated. Downstream targets of this pathway include genes that encode antioxidative enzymes such as Superoxide dismutase (SOD) whose transcription is activated when receptor activation by insulin/IGF is low or when sirtuins are active and the ability of cells to resist oxidative damage appears to determine their life span. Amongst dietary factors that activate sirtuins are certain polyphenols such as quercetin and resveratrol. Whereas their ability to affect life span has been demonstrated in simple organisms, their efficacy in mammals awaits proof of principle.
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PMID:Nutrition, sirtuins and aging. 1885 Feb 2

The aim of this study was to investigate biochemical and antioxidant parameters in alloxan-resistant (ALR) and alloxan-susceptible (ALS) rats. Diabetes was induced in 60-day-old male Wistar rats by a single intraperitonial injection of alloxan (AL, 150 mg/kg). Ten days after induction, a group of rats showed a significant decrease in glycemia. This group was named alloxan-resistant group. Susceptible rats showed a remarkable increase in the plasma lipid content, blood glucose and HbA1. Glycogen content in the liver decreased significantly in the ALS group (2.08 +/- 0.41 mg%) compared with ALR group (4.22 +/- 0.18). Aspartate aminotransferase and alanine aminotransferase activities were quantified in the plasma. Interestingly, ALR rats showed a decrease in both activities (42.1 +/- 6.11 and 21.7 +/- 5.54 U/mL) when compared with ALS rats (59.1 +/- 6.55 and 58.1 +/- 7.28 U/mL). The TBARS index was significantly increased in the ALS liver (0.38 +/- 0.08 nm/mg protein) when compared with the ALR liver (0.18 +/- 0.04). Superoxide dismutase and catalase activities in the ALR (230 +/- 13 and 131 +/- 15 U/mg protein) liver showed a marked increase when compared with the ALS liver (148 +/- 13 and 68 +/- 5 U/mg protein). The immunohistochemical and hematoxilin-eosin analysis also revealed that pancreatic islets of ALR rats display a different morphology amongst the groups. These results suggest an increased regenerative or recovery process in the ALR rat pancreatic islets and an increased hepatic antioxidant defenses in these group of alloxan-resistant rats.
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PMID:Pancreas beta-cells morphology, liver antioxidant enzymes and liver oxidative parameters in alloxan-resistant and alloxan-susceptible Wistar rats: a viable model system for the study of concepts into reactive oxygen species. 1904 70

Type 2 diabetes is a heterogeneous disease resulting from insulin resistance and/or from a beta-cell secretory defect. Hyperglycemia, which occurs during type 2 diabetes, causes disorders of oxidative-antioxidative balance in the cells, leading to increased free-radical formation. Reduced antioxidant capacity is supposed to be one of the causes of the occurrence of complications in type 2 diabetes. The aim of this study was to evaluate lipoperoxidation and plasma antioxidant status in patients with poorly controlled type 2 diabetes with or without complications. In this study, 15 patients with type 2 diabetes without complications and 11 patients with type 2 diabetes with complications were enrolled. The 'ferric-reducing ability of plasma' showed no differences between the two experimental groups. A small, nonsignificant, Superoxide dismutase (SOD) activity reduction was observed in patients with diabetes with complications when compared to those patients with diabetes without complications; on the contrary, we found increased lipoperoxidation in patients with diabetes with complications compared with those patients with diabetes without complications. We also observed a positive correlation between malondialdehyde levels and high density lipoprotein or vitamin E in all analyzed patients with type 2 diabetes. Data obtained from our study show that patients with poorly controlled type 2 diabetes with complications have higher lipoperoxidation than patients with complication-free diabetes, although a residual compensatory response to hyperglycemia-induced oxidative stress occurs.
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PMID:Lipoperoxidation and antioxidant capacity in patients with poorly controlled type 2 diabetes. 1965 6

Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. Oxidative stress has been demonstrated to be involved in the pathophysiology of age- or diabetes-related ED. Superoxide dismutase (SOD), an antioxidant enzyme catalyzing the conversion of superoxide anion (O(2) (-)) to hydrogen peroxide (H(2)O(2)) and molecular oxygen (O(2)), is a promising therapeutic target for ED. In vivo gene therapy and adult stem cell-based ex vivo gene therapy are two attractive current gene therapies for the treatment of ED. In this chapter we describe the use of two potent gene transfer techniques to deliver the therapeutic gene extracellular superoxide dismutase (ecSOD) into the penis of aged or diabetic rats for therapy of ED: adenoviral-mediated intracavernosal ecSOD gene transfer for gene therapy of ED and ecSOD gene-modified marrow stromal cells, also known as mesenchymal stem cells, based stem cell and gene therapy.
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PMID:Superoxide dismutase - a target for gene therapeutic approach to reduce oxidative stress in erectile dysfunction. 2001 81

Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO(3)(*-), peroxyl radical, and less efficiently H(2)O(2). By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and/or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds.
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PMID:Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential. 2111 Jul 89

It has been reported that high-dose salicylates, an IKKss inhibitor, may prevent FFAs-induced insulin resistance. In previous study, we found that in FFAs-induced insulin resistant rats, administration of salicylate was associated with a reduction of plasma malondialdehyde (MDA). In the present study, we investigated the effects of sodium salicylate on FFAs-induced insulin resistance and on oxidative stress in liver. Overnight-fasted Wistar rats were subject to 7h i.v. infusion of either saline or Intralipid plus 20U/ml heparin (IH) with or without salicylate. Hyperinsulinemic-euglycemic clamp with tracer infusion was performed to assess insulin-induced suppression of endogenous glucose production (EGP). Oxidative antioxidant markers, immunohistochemical inducible nitric oxide synthase (iNOS) stain, nitric oxide (NO), MDA, Superoxide dismutase (SOD) activity in liver was measured. Infusion of IH markedly decreased insulin-induced suppression of EGP, which were completely prevented by salicylate co-infusion. Furthermore, salicylate reversed IH-induced (1) increase in iNOS and NO expression in the liver; (2) increase in MDA/SOD in the liver. This study provides preliminary assessments of efficacy of sodium salicylate as a new treatment for FFAs-induced insulin resistances. The effect of increasing insulin sensitivity by salicylate in part may be secondary to reduce the oxidative stress in liver.
Diabetes Res Clin Pract 2010 Aug
PMID:Salicylate prevents hepatic oxidative stress activation caused by short-term elevation of free fatty acids in vivo. 2049 73


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