ascorbic-acid and Hyperglycemia

It is suggested that supplementation of vitamin C reduces hyperglycemia and lowers blood pressure in hypertensives by enhacing the formation of prostaglandin E1 (PGE1), PGI2 (prostacyclin), endothelial nitric oxide (eNO), and restore essential fatty acid (EFA) metabolism to normal and enhance the formation of lipoxin A4 (LXA4), a potent anti-inflammatory, vasodilator and antioxidant. These actions are in addition to the ability of vitamin C to function as an antioxidant. In vitro and in vivo studies revealed that PGE1, PGI2 and NO have cytoprotective and genoprotective actions and thus, protect pancreatic β and vascular endotheilial cells from the cytotoxic actions of endogenous and exogenous toxins. AA, the precursor of LXA4 and LXA4 have potent anti-diabetic actions and their plasma tissue concentrations are decreased in those with diabetes mellitus and hypertension. Thus, vitamin C by augmenting the formation of PGE1, PGI2, eNO, LXA4 and restoring AA content to normal may function as a cytoprotective, anti-mutagenic, vasodilator and platelet anti-agregator actions that explains its benefical action in type 2 diabetes mellitus and hypertension.

Topics: Alprostadil; Ascorbic Acid; Cytoprotection; Diabetes Mellitus, Type 2; Dietary Supplements; Epoprostenol; Fatty Acids, Essential; Humans; Hyperglycemia; Hypertension; Lipoxins; Nitric Oxide; Pancreas

Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Vascular endothelial dysfunction is an early pathophysiological precursor of cardiovascular disease. There is extensive evidence that hyperglycemia causes acute perturbations in endothelial function likely due to increases in oxidative damage. Interestingly, oscillating hyperglycemia may cause more damage than persistent hyperglycemia. Many, but not all, studies indicate that vascular endothelial dysfunction occurs early in the course of type 1 diabetes and is present even in adolescents. Ascorbic acid has been shown to diminish the acute effects of hyperglycemia on endothelial function in type 1 diabetes and in conjunction with euglycemia to restore endothelial function to normal values in adults with well-controlled diabetes. In vitro and in vivo animal evidence suggests potential benefit from two other small molecule antioxidants, nicotinamide and taurine. Early studies suggested that folate supplementation may improve endothelial function in adolescents with type 1 diabetes but this has not been confirmed by more recent studies. Epidemiological evidence suggests a possible role for vitamin D therapy although intervention studies in type 2 diabetes have yielded varying results and have not been done in type 1 diabetes. Further exploration of these and other compounds is clearly appropriate if we are to reduce cardiovascular risk in type 1 diabetes.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Dietary Supplements; Disease Progression; Endothelium, Vascular; Folic Acid; Humans; Hyperglycemia; Oxidative Stress; Taurine; Vitamin D

Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many phenotypic features of WS. Importantly, mutant Wrn(Deltahel/Deltahel) mice show abnormal increases in visceral fat deposition and fasting blood triglyceride levels followed by insulin resistance and high blood glucose levels. These mice also exhibit increased heart and liver tissue reactive oxygen species concomitantly with oxidative DNA damage, indicating a pro-oxidant status. We treated mice with either ascorbate or catechin hydrate for 9 months. Vitamin C supplementation reduced oxidative stress in liver and heart tissues and reversed hypertriglyceridemia, hyperglycemia, and insulin resistance and reduced fat weight in mutant Wrn(Deltahel/Deltahel) mice. Although the free scavenger catechin hydrate also reduced oxidative DNA damage in heart and liver tissues, it did not reverse any of the metabolic phenotype aspects in treated mutant mice. Finally, vitamin C and catechin hydrate did not affect the metabolic status of wild-type mice. These results indicate that vitamin C supplementation could be beneficial for WS patients.

Topics: Aging, Premature; Animals; Ascorbic Acid; Catechin; DNA Damage; DNA Helicases; Free Radical Scavengers; Humans; Hyperglycemia; Hypertriglyceridemia; Insulin Resistance; Mice; Mutation; Oxidative Stress; Reactive Oxygen Species; RecQ Helicases; Werner Syndrome; Werner Syndrome Helicase

Circulation on blood extracorporeally through plastic tubing activates several pathways including systemic inflammation and oxidative stress. These phenomena are suspected to participate to neurological and cardiovascular side effects observed in the patients under cardiopulmonary bypass (CPB). A direct relationship, in diabetic patients, between hyperglycemia and morbidity and mortality has been established. However, it is still unclear whether perioperative hyperglycemia has a direct effect on adverse events in cardiac surgery. The purpose of this study was to determine the influence of hyperglycemia on inflammation and oxidative stress in patients under CPB during cardiac surgery.. Control patients (n=17) and diabetic (type 2) patients (n=13) were included in this study. Blood samples were drawn before, during and after the CPB. Oxidative stress was evaluated in the plasma by direct and indirect approaches. Direct detection of ascorbyl radicals was assessed by electron spin resonance spectroscopy. An index: ascorbyl radical/vitamin C ratio is an indicator of the degree of oxidative stress taking place in the plasma. Oxygen radical absorbing capacity (ORAC) values were used as measurement of antioxidant capacity of the plasma. To determine inflammation profile of patients, we measure the evolution of plasma concentration of interleukin 8 (IL-8).. During cross clamping and post-CPB, the index ascorbyl radical/vitamin C is increased; the value of the index is more significant in diabetic patients. Concomitantly, ORAC values decreased in all the patients during cross clamping (p<0.05). Results concerning inflammatory index showed that IL-8 levels increased during the CPB.. In conclusion, the current study indicates that a systemic oxidative stress occurs during CPB and post-CPB periods and that in patients with type 2 diabetes mellitus, the systemic oxidative stress was increased.

Topics: Aged; Ascorbic Acid; Cardiopulmonary Bypass; Dehydroascorbic Acid; Diabetes Mellitus, Type 2; Electron Spin Resonance Spectroscopy; Female; Glycated Hemoglobin; Heart Valve Prosthesis Implantation; Humans; Hyperglycemia; Interleukin-8; Male; Middle Aged; Oxidative Stress

Diabetes represents a serious risk factor for the development of cardiovascular problems such as coronary heart disease, peripheral arterial disease, hypertension, stroke, cardiomyopathy, nephropathy and retinopathy. Identifying the pathogenesis of this increased risk provides a basis for secondary intervention to reduce morbidity and mortality in diabetic patients. Hyperglycemia and protein glycation, increased inflammation, a prothrombotic state and endothelial dysfunction have all been implicated as possible mechanisms for such complications. A linking element between many of these phenomena could possibly be, among other factors, increased production of reactive oxygen species. Vascular endothelial cells have several physiological actions that are essential for the normal function of the cardiovascular system. These include the production of nitric oxide (NO), which regulates vasodilatation, anticoagulation, leukocyte adhesion, smooth muscle proliferation and the antioxidative capacity of endothelial cells. However, under conditions of hyperglycemia, excessive amounts of superoxide radicals are produced inside vascular cells and this can interfere with NO production leading to the possible complications. This article aims at reviewing the links between reactive oxygen species, diabetes and vascular disease and whether or not antioxidants can alter the course of vascular complications in diabetic patients and animal models. A possible beneficial effect of antioxidants might present a new addition to the range of secondary preventive measures used in diabetic patients.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Complications; Dyslipidemias; Endothelium, Vascular; Glucose; Humans; Hyperglycemia; Hypertension; Insulin Resistance; Nitric Oxide; Oxidative Stress; Reactive Oxygen Species; Risk Factors; Vitamin E

Dehydroascorbic acid, the oxidized form of vitamin C, is transported into mammalian cells via facilitative glucose transporters and hyperglycemia inhibits this process by competitive inhibition. This inhibited transport may promote oxidative stress and contribute to the increase in atherosclerotic cardiovascular disease observed in patients with diabetes mellitus. This review explores the importance of this proposed mechanism in light of current research. For example, recent reports suggest that administration of antioxidants, such as vitamin C, may slow atherogenesis by improving endothelium-dependent vasodilation in individuals with abnormal glucose and lipid metabolism, perhaps by preventing the oxidation of nitric oxide, an important regulator of vasomotor tone. Endothelial dysfunction plays a key role in the development of atherosclerosis and endothelial cells may be particularly affected by hyperglycemia-induced ascorbic acid deficiency as they line the interior of blood vessels. In addition, we discuss evidence of several other mechanisms by which vitamin C status may affect the development of atherosclerotic cardiovascular disease, particularly its inverse relationship to multiple cardiovascular disease risk factors and indicators. Given these factors, vitamin C administration is recommended during periods of both acute and chronic hyperglycemia to help preserve endothelial function.

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Endothelium, Vascular; Humans; Hyperglycemia

It is generally accepted that high glucose levels for many years are a primary cause of most long-term complications in diabetic patients. Many studies suggest that the central features of diabetic complications are caused by the hyperglycaemia-accelerated formation of non-enzymatic glycated products. Non-enzymatic glycation, however, has been recently demonstrated to be linked to glucose auto-oxidative process. At the same time glycated proteins have been shown to be a source of free radicals. These findings raised the hypothesis of a link between oxidative stress and the development of diabetic complications. Some studies have recently demonstrated that antioxidants, such as vitamin C and E, may reduce in vitro and in vivo protein glycation. At the same time some antioxidants act as scavengers of the free radicals produced by non-enzymatic glycation in vitro. Such studies may lead to therapeutic approaches for limiting the damage from glycation and oxidation reactions and for complementing existing therapy for treatment of the complications of diabetes.

Topics: Ascorbic Acid; Diabetes Complications; Glucose; Glycation End Products, Advanced; Humans; Hyperglycemia; Oxidative Stress; Vitamin E

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Diabetes Mellitus; Drug Synergism; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin

Topics: Ascorbic Acid; Blood Bactericidal Activity; Diabetes Complications; Diabetic Ketoacidosis; Humans; Hyperglycemia; Phagocytosis; Postoperative Care; Preoperative Care; Surgery, Oral; Tooth Extraction; Vitamin D

The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.. To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock.. Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019.. Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102).. The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses.. Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively).. In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock.. ClinicalTrials.gov Identifier: NCT03389555.

Topics: Adrenal Cortex Hormones; Adult; Aged; Ascorbic Acid; Cross Infection; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypernatremia; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Proportional Hazards Models; Shock, Septic; Thiamine; Treatment Failure

Hypoglycemia produces thrombosis activation, but little attention has been paid to the effects of hyperglycemia following recovery from hypoglycemia on thrombosis activation.. In both twenty-two healthy subjects and twenty-one matched persons with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normo-glycemia or hyperglycemia for another 2 h. After this, normal glycemia was maintained for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. In both controls and people with diabetes, the recovery with normo-glycemia was accompanied by a significant improvement of Von Willebrand factor (vWF), prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III-complexes (TAT), P-selectin, plasminogen activator inhibitor-1 (PAI-1), nitrotyrosine and 8-iso-prostaglandin F2α (8-iso-PGF2α) (p < 0.01 vs hypoglycemia for all the parameters), all directly affected by hypoglycemia itself (p < 0.01 vs baseline for all the parameters). On the contrary, the recovery with hyperglycemia after hypoglycemia worsens all these parameters (p < 0.01 vs normoglycemia for all the parameters), an effect persisting even after the additional 6 h of normo-glycemia. The effect of hyperglycemia following hypoglycemia was partially counterbalanced when vitamin C was infused (p < 0.01 vs hyperglycemia alone for all the parameters), suggesting that hyperglycemia following hypoglycemia may activate thrombosis through the oxidative stress production.. This study shows that, in type 1 diabetes as well as in controls, the way in which recovery from hypoglycemia takes place could play an important role in favoring the activation of thrombosis and oxidative stress, widely recognized cardiovascular risk factors.

Topics: Adult; Antithrombin III; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprost; Endothelium, Vascular; Female; Healthy Volunteers; Humans; Hyperglycemia; Hypoglycemia; Male; Oxidative Stress; P-Selectin; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Protein Precursors; Prothrombin; Thrombosis; von Willebrand Factor; Young Adult

It has been reported that hyperglycemia following hypoglycemia produces an ischemia-reperfusion-like effect in type 1 diabetes. In this study the possibility that GLP-1 has a protective effect on this phenomenon has been tested.. 15 type 1 diabetic patients underwent to five experiments: a period of two hours of hypoglycemia followed by two hours of normo-glycemia or hyperglycemia with the concomitant infusion of GLP-1 or vitamin C or both. At baseline, after 2 and 4 hours, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2alpha, sCAM-1a, IL-6 and flow mediated vasodilation were measured.. After 2 h of hypoglycemia, flow mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine and IL-6 significantly increased. While recovering with normoglycemia was accompanied by a significant improvement of endothelial dysfunction, oxidative stress and inflammation, a period of hyperglycemia after hypoglycemia worsens all these parameters. These effects were counterbalanced by GLP-1 and better by vitamin C, while the simultaneous infusion of both almost completely abolished the effect of hyperglycemia post hypoglycemia.. This study shows that GLP-1 infusion, during induced hyperglycemia post hypoglycemia, reduces the generation of oxidative stress and inflammation, improving the endothelial dysfunction, in type 1 diabetes. Furthermore, the data support that vitamin C and GLP-1 may have an additive protective effect in such condition.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprost; Female; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inflammation; Inflammation Mediators; Infusions, Parenteral; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Oxidative Stress; Reperfusion Injury; Time Factors; Treatment Outcome; Tyrosine; Vasodilation; Young Adult

Postprandial hyperglycemia induces oxidative stress responses, impairs vascular endothelial function (VEF) and increases the risk of cardiovascular disease. We hypothesized that the antioxidant and anti-inflammatory activities of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) would protect against vascular dysfunction that is otherwise caused by postprandial hyperglycemia by decreasing oxidative stress and proinflammatory responses, and improving nitric oxide (NO•) homeostasis. In a randomized, crossover study, healthy men (n=15; 21.8 ± 0.8 years) completed a fasting oral glucose challenge (75 g) with or without prior supplementation of γ-TmT (5 days). Brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine and asymmetric dimethylarginine (ADMA) were measured at regular intervals during a 3-h postprandial period. Supplementation of γ-TmT increased (P<.05) plasma γ-T by threefold and γ-carboxyethyl-hydroxychroman by more than ninefold without affecting α-T, glucose, arginine or ADMA. Baseline FMD, MDA, arginine and ADMA were unaffected by γ-TmT (P>.05). Postprandial FMD decreased 30%-44% (P<.05) following glucose ingestion, but was maintained with γ-TmT. Supplementation of γ-TmT also attenuated postprandial increases in MDA that occurred following glucose ingestion. Plasma arginine decreased (P<.05) in both trials to a similar extent regardless of γ-TmT supplementation. However, the ratio of ADMA/arginine increased time-dependently in both trials (P<.05), but to a lesser extent following γ-TmT supplementation (P<.05). Inflammatory proteins were unaffected by glucose ingestion or γ-TmT. Collectively, these findings support that short-term supplementation of γ-TmT maintains VEF during postprandial hyperglycemia possibly by attenuating lipid peroxidation and disruptions in NO• homeostasis, independent of inflammation.

Topics: Adolescent; Adult; Antioxidants; Arginine; Ascorbic Acid; Blood Glucose; Brachial Artery; Dietary Supplements; Endothelium, Vascular; gamma-Tocopherol; Humans; Hyperglycemia; Insulin; Male; Malondialdehyde; Nitric Oxide; Oxidative Stress; Tocopherols; Uric Acid; Young Adult

Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia-reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.

Topics: Adult; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Cross-Over Studies; Diabetes Mellitus, Type 1; Endothelium, Vascular; Female; Glucose; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inflammation Mediators; Infusions, Intravenous; Insulin; Male; Oxidative Stress; Risk Factors; Vasodilation; Young Adult

Mortality increases when acute coronary syndromes are complicated by stress-induced hyperglycemia. Early pulse wave reflection can augment central aortic systolic blood pressure and increase left ventricular strain. Altered pulse wave reflection may contribute to the increase in cardiac risk during acute hyperglycemia. Chronic ascorbic acid (AA) supplementation has recently been shown to reduce pulse wave reflection in diabetes. We investigated the in vivo effects of acute hyperglycemia, with and without AA pretreatment, on pulse wave reflection and arterial hemodynamics. Healthy male volunteers were studied. Peripheral blood pressure (BP) was measured at the brachial artery, and the SphygmoCor pulse wave analysis system was used to derive central BP, the aortic augmentation index (AIx; measure of systemic arterial stiffness), and the time to pulse wave refection (Tr; measure of aortic distensibility) from noninvasively obtained radial artery pulse pressure (PP) waveforms. Hemodynamics were recorded at baseline and then every 30 min during a 120-min systemic hyperglycemic clamp (14 mmol/l). The subjects, studied on two separate occasions, were randomized in a double-blind, crossover manner to placebo or 2 g intravenous AA before the initiation of hyperglycemia. During hyperglycemia, AIx increased and Tr decreased. Hyperglycemia did not change peripheral PP but did magnify central aortic PP and diminished the normal physiological amplification of PP from the aorta to the periphery. Pulse wave reflection, as assessed from peripheral pulse wave analysis, is enhanced during acute hyperglycemia. Pretreatment with AA prevented the hyperglycemia-induced hemodynamic changes. By protecting hemodynamics during acute hyperglycemia, AA may have therapeutic use.

Topics: Acute Disease; Adult; Antioxidants; Aorta; Arteries; Ascorbic Acid; Blood Pressure; Brachial Artery; Cross-Over Studies; Double-Blind Method; Elasticity; Glucose Clamp Technique; Hemodynamics; Humans; Hyperglycemia; Injections, Intravenous; Male; Pulse; Radial Artery

Endothelium-dependent vasodilation is impaired in patients with insulin-dependent and non-insulin-dependent diabetes mellitus and restored by vitamin C administration, implicating a causative role for oxidant stress. Hyperglycemia per se attenuates endothelium-dependent vasodilation in healthy subjects. Accordingly, this study investigated whether impaired endothelium-dependent vasodilation caused by hyperglycemia in nondiabetic humans is restored by administration of the antioxidant vitamin C.. Endothelium-dependent vasodilation was measured by incremental brachial artery administration of methacholine chloride (0.3 to 10 microg/min) during euglycemia, after 6 hours of hyperglycemia (300 mg/dL) created by dextrose (50%) intra-arterial infusion, and with coadministration of vitamin C (24 mg/min) during hyperglycemia. Endothelium-dependent vasodilation was significantly diminished by hyperglycemia (P:=0.02 by ANOVA) and restored by vitamin C (P:=0.04). In contrast, endothelium-dependent vasodilation was not affected by equimolar infusions of mannitol, with and without vitamin C coinfusion (P:=NS). Endothelium-independent vasodilation was measured by incremental infusion of verapamil chloride (10 to 300 microg/min) without and with coadministration of N:(G)-monomethyl-L-arginine (L-NMMA). In the absence of L-NMMA, endothelium-independent vasodilation was not significantly altered during hyperglycemia (P:=NS) but was augmented by vitamin C (P:=0.04). The coadministration of L-NMMA eliminated the vitamin C-related augmentation in verapamil-mediated vasodilation.. Vitamin C administration restores endothelium-dependent vasodilation impaired by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia may contribute in part to impaired vascular function through production of superoxide anion.

Topics: Acute Disease; Adult; Ascorbic Acid; Blood Flow Velocity; Blood Glucose; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Forearm; Glucose; Glucose Clamp Technique; Hemodynamics; Humans; Hyperglycemia; Infusions, Intra-Arterial; Male; Methacholine Chloride; Nitric Oxide; Osmolar Concentration; Vasodilation; Verapamil

The goal of this study was to determine whether postprandial hyperglycemia, induced by oral glucose loading, attenuates endothelial function in healthy subjects without diabetes and whether coadministration of vitamins C and E could prevent these postprandial changes.. Epidemiologic evidence suggests that postprandial hyperglycemia, below diabetic levels, is a risk factor for cardiovascular disease. Postprandial hyperglycemia may promote atherosclerosis through endothelial dysfunction and oxidative stress.. We evaluated the acute effects of oral glucose loading (75 g), alone and with vitamins C (2 g) and E (800 IU), on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery, in a randomized, double-blind, placebo-controlled, crossover study of 10 healthy volunteers. Changes in the levels of markers of oxidative stress (plasma malondialdehyde and erythrocyte glutathione, glutathione peroxidase and superoxide dismutase) were also assessed.. Increases in plasma glucose and insulin after glucose loading were unaffected by vitamin coadministration. With glucose loading alone, FMD fell from 6.5+/-2.2 at baseline to 5.4+/-1.7, 3.7+/-2.1*, 4.1+/-3.5* and 5.7+/-1.9% at 1, 2, 3 and 4 h (*p < 0.05 vs. 0 h). In contrast, FMD did not change significantly after glucose plus vitamins (6.4+/-1.3, 7.6+/-1.8, 7.9+/-2.7, 6.9+/-2.3, 6.9+/-1.9% at 0, 1, 2, 3 and 4 h). By two-way repeated measures analysis of variance we found a significant interaction between vitamin treatment and time (p = 0.0003), indicating that vitamins prevented the glucose-induced attenuation of FMD. Oxidative stress markers did not significantly change with glucose loading alone or with vitamins.. Oral glucose loading causes an acute, transient decrease of FMD in healthy subjects without diabetes, which is prevented by vitamins C and E.

Topics: Adult; Ascorbic Acid; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hyperglycemia; Male; Oxidative Stress; Postprandial Period; Vasodilation; Vitamin E

We reviewed the clinical data relating to the efficacy and safety of pharmacologic doses of ascorbic acid in the prevention and treatment of the common cold. Although one study tentatively supports the hypothesis that such doses of ascorbic acid may be efficacious, a second study by the same group did not confirm the significant findings, and no clear, reproducible pattern of efficacy has emerged from the review of all the evidence. Similarly, there is currently little adequate evidence on either the presence or the absence of serious adverse reactions to such doses of ascorbic acid, although many such reactions have been hypothesized. The unrestricted use of ascorbic acid for these purposes cannot be advocated on the basis of the evidence currently available.

Topics: Administration, Oral; Animals; Ascorbic Acid; Clinical Trials as Topic; Common Cold; Digestive System; Drug Interactions; Female; Fetus; Flavonoids; Guinea Pigs; Humans; Hyperglycemia; Injections, Intravenous; Injections, Subcutaneous; Male; Maternal-Fetal Exchange; Placebos; Pregnancy; Rats; Time Factors; Urinary Calculi

Oxidative and endoplasmic reticulum stresses contribute to the pathogenesis of β-cell dysfunction in diabetes mellitus. This study investigates the effect of isopulegol on the above stresses in HFD/STZ induced diabetic rats.. Animals in group I and II were placed in normal pellet diet and group II was treated with isopulegol at 200 mg/kg b.w. Animals in groups III-V were placed in HFD for 4 weeks and made diabetic with single intraperitoneal injection of STZ (35 mg/kg b.w) in 0.1 M citrate buffer (pH 4.5). Group III served as diabetic control while animals in group IV and V were treated with isopulegol (100 mg/kg b.w) and metformin (25 mg/kg b.w) respectively for 28 d.. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione sulphur transferase (GST), glutathione reductase (GR) and the levels of vitamin-E, vitamin-C, reduced glutathione (GSH) were significantly (p <0.05) decreased in plasma and tissues of diabetic rats. Thiobarbituric acid reactive acid substances (TBARS) and lipid hydroperoxides (LHP), indices of lipid peroxidation were also significantly (p <0.05) increased in diabetic rats. In pancreatic tissue ER stress markers PERK, elf2α, ATF4 and in hepatic tissue oxidative stress marker UCP-2 expression was significantly (p <1.0) increased in diabetic rats. Administration of isopulegol significantly improved antioxidant status and decreased oxidative and ER stress markers in diabetic treated rats. Histopathological studies on liver and kidney supported the above findings. The results are comparable with the standard drug metformin.. Isopulegol a naturally occurring monoterpene alcohol attenuated oxidative and ER stress in HFD/STZ induced diabetic rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Catalase; Cyclohexane Monoterpenes; Diabetes Mellitus, Experimental; Endoplasmic Reticulum Stress; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Hyperglycemia; Hypoglycemic Agents; Insulin; Lipid Peroxidation; Lipid Peroxides; Male; Oxidative Stress; Rats; Rats, Wistar; Streptozocin; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Hyperglycemia-induced inflammation can greatly increase the risk of periodontal disease in people with diabetes. Low-level laser irradiation (LLLI) has been used for wound healing and anti-inflammation in many cases, and LLLI is known to inhibit the lipopolysaccharide (LPS)-stimulated inflammatory response. However, the therapeutic effect of LLLI in diabetes patients with periodontitis remains unknown. In this study, we cultured human gingival fibroblasts (HGFs) in high-glucose medium (35 mM) to mimic a hyperglycemic environment, and then measured the anti-inflammatory effect of LLLI by assessing the expression of pro-inflammatory genes including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 by quantitative real-time polymerase chain reaction. The results demonstrated no significant inflammatory response in HGFs cultured in mannitol medium and in those treated only with LLLI. However, HGFs cultured only in high-glucose medium showed significantly higher expression of pro-inflammatory cytokine than in those treated together with LLLI. We then observed that LLLI reduced the expression of pro-inflammatory cytokines in HGFs cultured in high-glucose medium by modulating cAMP signaling. We also investigated whether antioxidant (vitamin C) treatment reduced the inflammatory effect of oxidative stress in HGFs cultured in high-glucose medium but found no additive effect upon co-treatment with LLLI, suggesting that LLLI may activate cAMP signaling, but not reactive oxygen species (ROS) signaling, to reduce the high glucose-induced inflammation. In conclusion, LLLI may have an anti-inflammatory effect on HGFs in a high glucose environment and may benefit the treatment of periodontal disease in diabetes patients.

Topics: Ascorbic Acid; Cell Death; Cell Survival; Cells, Cultured; Cytokines; Fibroblasts; Gingiva; Humans; Hyperglycemia; Inflammation; Inflammation Mediators; Low-Level Light Therapy; RNA, Messenger

To examine the effect of galangin on hyperglycemia-mediated oxidative stress in streptozotocin (STZ)-induced diabetic rats.. Diabetes was induced by intraperitoneal administration of low-dose STZ (40 mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8 mg/kg BW) or glibenclamide (600 µg/kg BW) was given orally, once daily for 45 days to normal and STZ-induced diabetic rats.. Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes. The levels of insulin and non-enzymatic antioxidants (vitamin C, vitamin E, reduced glutathione) and the activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase (GST)) were decreased significantly in diabetic control rats. These altered plasma glucose, insulin, lipid peroxidation products, enzymatic and non-enzymatic antioxidants ions were reverted to near-normal level after the administration of galangin and glibenclamide.. The present study shows that galangin decreased oxidative stress and increased antioxidant status in diabetic rats, which may be due to its antidiabetic and antioxidant potential.

Topics: Animals; Antioxidants; Ascorbic Acid; Diabetes Mellitus, Experimental; Flavonoids; Hyperglycemia; Lipid Peroxidation; Male; Oxidation-Reduction; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Streptozocin; Vitamin E

Clinical and experimental evidence suggests that hyperglycaemia is responsible for the oxidative stress in diabetes mellitus. The study was designed to investigate the comparative effects of probiotic and vitamin C (Vit-C) treatments on hyperglycaemia, oxidative stress and dyslipidaemia in alloxan-induced diabetic rats. Type 1 diabetes (T1DM) was induced in male Wistar rats by a single intraperitoneal (i.p.) injection of alloxan (150 mg/kg). Six groups of the animals received the following treatment regimens for four weeks: (1) Normal saline, per os; (2) alloxan (150 mg/kg, i.p.); (3) alloxan (150 mg/kg) + insulin (4 U/kg, subcutaneously); (4) alloxan (150 mg/kg) + probiotic (4.125 × 10⁶ CFU/100 mL per os); (5) alloxan (150 mg/kg) + Vit-C (100 mg/kg, i.m.); (6) alloxan (150 mg/kg) + probiotic (4.125 × 10⁶ CFU/100 mL per os) + Vit-C (100 mg/kg, intramuscularly). Probiotic + Vit-C decreased (p < 0.05) blood glucose concentration in diabetic treated group, when compared with the untreated diabetic group. Probiotic + Vit-C reduced malondialdehyde concentration, in the serum, brain and kidneys, respectively, but increased the activity of antioxidant enzymes. Probiotic and Vit-C may be more effective than Vit-C alone, in ameliorating hyperglycaemia, oxidative stress and dyslipidaemia in alloxan-induced diabetic rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Experimental; Dyslipidemias; Hyperglycemia; Insulin; Lipid Peroxidation; Male; Malondialdehyde; Oxidative Stress; Probiotics; Random Allocation; Rats; Rats, Wistar

There is mounting evidence demonstrating causative links between hyperglycemia, oxidative stress, and insulin resistance, the core pathophysiological features of type 2 diabetes mellitus. Using a combinational approach, we synthesized a vanadium-antioxidant (i.e., l-ascorbic acid) complex and examined its effect on insulin resistance and oxidative stress. This study was designed to examine whether vanadyl(IV)-ascorbate complex (VOAsc) would reduce oxidative stress, hyperglycemia, and insulin resistance in high-fat high-sucrose diet (HFSD)-induced type 2 diabetes in mice. Male C57BL/6J mice were fed a HFSD for 12 weeks to induce insulin resistance, rendering them diabetic. Diabetic mice were treated with rosiglitazone, sodium l-ascorbate, or VOAsc. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index, and serum adipocytokine levels were measured. Serum levels of nitric oxide (NO) parameters were also determined. The liver was isolated and used for determination of malondialdehyde, reduced glutathione, and catalase levels, and superoxide dismutase and glutathione peroxidase activities. VOAsc groups exhibited significant reductions in serum adipocytokine and NO levels, and oxidative stress parameters compared to the corresponding values in the untreated diabetic mice. The results indicated that VOAsc is non-toxic. In conclusion, we identified VOAsc as a potentially effective adjunct therapy for the management of type 2 diabetes.

Topics: Adiponectin; Adipose Tissue; Animals; Ascorbic Acid; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diet, High-Fat; Feeding Behavior; Glucose Tolerance Test; Homeostasis; Hyperglycemia; Insulin; Insulin Resistance; Leptin; Liver; Male; Malondialdehyde; Mice, Inbred C57BL; Nitric Oxide; Organ Size; Oxidative Stress; Resistin; Sucrose; Tumor Necrosis Factor-alpha; Vanadates

Thiazole derivatives are attractive candidates for drug development because they can be efficiently synthesized and are active against a number of diseases and conditions, including diabetes. In our present study, we investigated the anti-inflammatory and antioxidant properties of N-adamantyl-4-methylthiazol-2-amine (KHG26693), a new thiazole derivative, in a streptozotocin (STZ)-induced model of diabetes mellitus. STZ-induced diabetic rats were intraperitoneally administered KHG26693 (3mg/kg-body weight/day) for 4 weeks. KHG26693 administration significantly decreased blood glucose, triglycerides, and cholesterol and increased insulin. KHG26693 also suppressed several inflammatory responses in STZ-induced diabetic rats, as evidenced by decreased levels of serum tumor necrosis factor-α, interleukin-1β, and nitric oxide. Additionally, KHG26693 significantly modulated hepatic lipid peroxidation, catalase and superoxide dismutase activity, and the nonenzymatic antioxidant status (e.g., vitamins C and E), and reduced the glutathione content. These anti-inflammatory/antioxidative actions occurred as a result of the downregulation of inducible nitric oxide synthase and nuclear factor-kappa B. Taken together, our results suggest that KHG26693 successfully reduces the production of oxidative stress in STZ-induced diabetic rats by regulating the oxidation-reduction system, specifically increasing antioxidant capacity. Furthermore, KHG26693 treatment significantly reverted the key enzymes of glucose metabolism, such as glucokinase, glucose-6-phosphatase, glycogen synthase, glycogen phosphorylase, and fructose-1,6-bisphosphatase, to near-normal levels in liver tissues. These results indicate that KHG26693 normalizes disturbed glucose metabolism by enhancing glucose utilization and decreasing liver glucose production via insulin release, suggesting the possibility of future diabetes treatments.

Topics: Adamantane; Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Blood Glucose; Catalase; Diabetes Mellitus, Experimental; Glutathione; Hyperglycemia; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Insulin; Interleukin-1beta; Lipid Metabolism; Lipid Peroxidation; Liver; Male; Malondialdehyde; NF-kappa B; Nitric Oxide; Oxidative Stress; Rats, Sprague-Dawley; Superoxide Dismutase; Thiazoles; Tumor Necrosis Factor-alpha; Vitamin E

Hyperglycemia leads to the formation of free radicals and advanced glycation end-products (AGEs). Antioxidants can reduce the level of protein glycation and DNA damage. In this study, we compared the levels of vitamin C intake, which is among the most abundant antioxidants obtained from diet, with the levels of fasting plasma glucose (FPG), glycated hemoglobin (A1C), DNA damage, and cytotoxicity in prediabetic subjects and type 2 diabetic subjects. Our results indicated that there was no significant correlation between FPG or A1C and DNA damage parameters (micronuclei, nucleoplasmic bridges, and nuclear buds). FPG and A1C correlated with necrosis (r = 0.294; P = 0.013 and r = 0.401; P = 0.001, resp.). Vitamin C intake correlated negatively with necrosis and apoptosis (r = -0.246; P = 0.040, and r = -0.276; P = 0.021, resp.). The lack of a correlation between the FPG and A1C and DNA damage could be explained, at least in part, by the elimination of cells with DNA damage by either necrosis or apoptosis (cytotoxicity). Vitamin C appeared to improve cell survival by reducing cytotoxicity. Therefore, the present results indicate the need for clinical studies to evaluate the effect of low-dose vitamin C supplementation in type 2 diabetes.

Topics: Adult; Apoptosis; Ascorbic Acid; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Dietary Supplements; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Middle Aged; Necrosis; Prediabetic State

Diabetes mellitus is the most common serious metabolic disorder and it is considered to be one of the five leading causes of death in the world. Hyperglycemia-mediated oxidative stress plays a crucial role in diabetic complications. Hence, this study was undertaken to evaluate the protective effect of esculetin on the plasma glucose, insulin levels, tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. Extent of oxidative stress was assessed by the elevation in the levels of lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD); reduction in the enzymic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST); nonenzymic antioxidants Vitamin C, E and reduced glutathione (GSH) were observed in the liver and kidney tissues of diabetic control rats as compared to control rats. Oral supplementation of esculetin to diabetic rats for 45 days significantly brought back lipid peroxidation markers, enzymic and nonenzymic antioxidants to near normalcy. Moreover, the histological observations evidenced that esculetin effectively rescues the hepatocytes and kidney from hyperglycemia mediated oxidative damage without affecting its cellular function and structural integrity. These findings suggest that esculetin (40 mg/kg BW) treatment exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic and renal tissues. Further, detailed studies are in progress to elucidate the molecular mechanism by which esculetin elicits its modulatory effects in insulin signaling pathway.

Topics: Administration, Oral; Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Catalase; Diabetes Mellitus, Experimental; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Hyperglycemia; Insulin; Kidney; Lipid Peroxidation; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Umbelliferones; Vitamin E

Chromium picolinate is advocated as an anti-diabetic agent for impaired glycemic control. It is a transition metal that exists in various oxidation states and may thereby act as a pro-oxidant. The present study has been designed to examine the effect of chromium picolinate supplementation on hyperglycemia-induced oxidative stress. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (50mg/kg body weight) and chromium was administered orally as chromium picolinate (1mg/kg body weight) daily for a period of four weeks after the induction of diabetes. As is characteristic of diabetic condition, hyperglycemia was associated with an increase in oxidative stress in liver in terms of increased lipid peroxidation and decreased glutathione levels. The activity of antioxidant enzymes like superoxide dismutase, catalase and glutathione reductase were significantly reduced in liver of diabetic animals. Levels of α-tocopherol and ascorbic acid were found to be considerably lower in plasma of diabetic rats. Chromium picolinate administration on the other hand was found to have beneficial effect in normalizing glucose levels, lipid peroxidation and antioxidant status. The results from the present study demonstrate potential of chromium picolinate to attenuate hyperglycemia-induced oxidative stress in experimental diabetes.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Experimental; Glutathione; Hyperglycemia; Lipid Peroxidation; Liver; Male; Oxidative Stress; Picolinic Acids; Rats; Rats, Wistar; Transaminases

To determine whether acute ascorbic acid infusions alter the effect of hyperglycemia on endothelial function in adolescents with type 1 diabetes.. The forearm blood flow (FBF) reactive hyperemic response to 5 min of upper arm occlusion was studied in eight adolescents with type 1 diabetes during euglycemic and hyperglycemic insulin clamp (40 mU/m2/min) with and without ascorbic acid infusion (3 mg/min).. The ratio of post- to preocclusion FBF decreased during hyperglycemia without ascorbic acid (p = 0.013), but did not change during hyperglycemia with ascorbic acid. The changes during hyperglycemia were different between the two studies (p = 0.038). Similar results were found when the percent change in forearm vascular resistance following occlusion was assessed.. These results indicate that antioxidant treatment with ascorbic acid blocks acute hyperglycemic impairment of endothelial function in adolescents with type 1 diabetes.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Blood Flow Velocity; Constriction; Diabetes Mellitus, Type 1; Endothelium; Female; Forearm; Glucose Clamp Technique; Humans; Hyperemia; Hyperglycemia; Insulin; Male; Vasodilation

Reactive oxygen species play an important role in the pathogenesis of organ damage in diabetes mellitus. Streptozotosin (STZ) is a commonly employed compound to produce diabetes mellitus and these animals exhibit most of diabetic complications.. In our study, diabetes was induced by a single intraperitoneal injection of STZ at a dose of 50 mg/kg in rats and they were killed 12 weeks after STZ. Endogenous lipid peroxide levels, enzymatic and non-enzymatic antioxidants were measured in liver, heart, kidney, brain, and testis tissues to investigate the effect of long-term hyperglycemic state. The susceptibility of diabetic tissues to oxidative stress was also examined in in vitro oxidizing system containing ascorbic acid and iron.. We found that prooxidant and antioxidant balance has changed in favor of prooxidation in the tissues of diabetic rats. The susceptibility of liver to oxidative stress increased; however, this susceptibility did not change in heart, kidney, brain, and testis of diabetic rats.. Our results indicate that long-term hyperglycemic state disturbs hepatic prooxidant-antioxidant balance at an earlier period and more pronouncedly than other tissues.

Topics: Animals; Antioxidants; Ascorbic Acid; Diabetes Mellitus, Experimental; Hyperglycemia; Iron; Liver; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase

Hyperglycemia can impair the male reproductive system in experimental animals and in men during reproductive age. Studies have shown that vitamin C has some good effects on male reproductive system, and therefore vitamin C treatment could attenuate the dysfunctions in this system caused by hyperglycemia. Thus, the objective of this work was to evaluate whether vitamin C treatment could attenuate reproductive dysfunctions in hyperglycemic male rats.. Adult male rats were divided into 3 groups: a normoglycemic (n = 10) and two hyperglycemic (that received a single dose of streptozotocin - 40 mg/kg BW). The two last groups (n = 10 per group) were divided into: hyperglycemic control (Hy) and hyperglycemic + 150 mg of vitamin C (HyC), by gavage during 30 consecutive days. The normoglycemic and hyperglycemic control groups received the vehicle (water). The first day after the treatment, the rats were anesthetized and killed to evaluate oxidative stress biomarkers (TBARS, SOD, GSHt and GSH-Px) in the erythrocytes, body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology.. Compared with the normoglycemic animals, hyperglycemic control rats showed reduced weight of the body and reproductive organ but testis weight was maintained. It was also observed reduction of testosterone and LH levels, seminiferous tubular diameter, sperm motility and sperm counts in the epididymis. In addition, there was an increase in morphological abnormalities on spermatozoa as well as in oxidative stress level. Vitamin C reduced the oxidative stress level, diminished the number of abnormal sperm, and increased testosterone and LH levels and seminiferous tubular diameter but did not show improvement of sperm motility in relation to the hyperglycemic control group. Hyperglycemia caused a rearrangement in the epididymal tissue components (stroma, ephitelium and lumen) as demonstrated by the stereological analysis results. However, this alteration was partially prevented by vitamin C treatment.. We conclude that vitamin C partially attenuated some male reproductive system dysfunctions in hyperglycemic rats.

Topics: Animals; Ascorbic Acid; Epididymis; Hyperglycemia; Luteinizing Hormone; Male; Oxidative Stress; Rats; Rats, Wistar; Reproduction; Sexual Dysfunction, Physiological; Spermatozoa; Streptozocin; Testosterone

Diabetic neuropathy can affect the male reproductive system. The aim of this study was therefore to evaluate whether antioxidant (vitamins C and/or E) treatment could attenuate reproductive dysfunctions in hyperglycemic adult male rats. The animals were randomly assigned to one of four experimental groups: hyperglycemic control (Hy), hyperglycemic + 150 mg/day vitamin C (HyC), hyperglycemic + 100 mg/day vitamin E (HyE) or hyperglycemic + vitamins C and E (HyCE). The normoglycemic group (n = 10) received only the vehicles. The testosterone level and noradrenergic response of the vas deferens were analyzed. Both vitamins significantly decreased the TBARS (thiobarbituric acid reactive species) level in the hyperglycemic groups. There was a significant reduction in the testosterone level in the Hy and HyE groups when compared to the normoglycemic group. However, the testosterone levels were partially recovered in the HyC and HyCE groups. In addition, an increased sensitivity of the α-1 adrenoceptor in the vas deferens of the hyperglycemic control group was observed. Treatment with vitamins partially restored (vitamin E or in combination with vitamin C) or totally (vitamin C alone) this dysfunction. Moreover, the maximum response values to norepinephrine were similar among all groups. Thus, we concluded that vitamin C is more efficient than vitamin E in attenuating the effects of hyperglycemia on the male reproductive system of adult rats.

Topics: Androgens; Animals; Antioxidants; Ascorbic Acid; Diabetic Neuropathies; Hyperglycemia; Male; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Testosterone; Thiobarbituric Acid Reactive Substances; Vas Deferens; Vitamin E

Hyperglycemia-induced endothelial cell dysfunction can be the result of increased oxidative stress and concomitant increase in endoplasmic reticulum (ER) stress. To test the extent of coupling between these two stresses, the effect of antioxidant vitamins on glucose-induced oxidative stress and ER stress in endothelial cells were studied.. Human umbilical vein endothelial cells (HUVEC) were treated with physiological (5.5mM) or supra-physiological (27.5mM) dextrose concentrations, and ER stress and oxidative stress were measured. Additional experiments were carried out in HUVEC over-expressing exogenous glucose transporter-1 (Glut-1) and treated with 5.5mM dextrose.. Supra-physiological dextrose concentrations increased both ER stress and oxidative stress. However, while oxidative stress could be effectively inhibited with alpha-tocopherol and ascorbic acid, these antioxidants had no effect on ER stress. Increasing intracellular glucose levels by exogenous expression of Glut-1 in endothelial cells also increased oxidative stress and ER stress. Whereas the oxidative stress in these cells was reduced with alpha-tocopherol and ascorbic acid and dimethylsulfoxide, the ER stress could not be ameliorated with alpha-tocopherol and ascorbic acid.. These results indicate that ER stress can be uncoupled from oxidative stress and antioxidants can ameliorate the latter without altering the ER stress induced by hyperglycemia.

Topics: Alkaline Phosphatase; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Cell Division; Endothelial Cells; Endothelium, Vascular; Female; Glucose; Glucose Transporter Type 1; Humans; Hyperglycemia; Kinetics; Oxidative Stress; Phenanthridines; Placenta; Pregnancy; Reactive Oxygen Species; Umbilical Veins

To investigate the possibility of reversing endothelial dysfunction and inflammation by glucose normalization, antioxidants and insulin per se, in different subgroups of Type 1 diabetic patients.. Three subgroups of Type 1 diabetic patients were studied: patients within 1 month of diagnosis (subgroup 1); patients with approximately 5 years' disease duration and with glycated haemoglobin (HbA(1c)) 7.0% since diagnosis (subgroup 3). Participants underwent four procedures: 2-h hyperglycaemic clamp followed by: (A) 12 h near-normalization of blood glucose, with the addition of vitamin C during the last 6 h; (B) 12-h vitamin C and near-normalization of blood glucose for the last 6 h; (C) both vitamin C and near-normalization of blood glucose for 12 h; (D) hyperglycaemic-hyperinsulinaemic clamp for 12 h, with the addition of vitamin C during the last 6 h.. After 2 h of hyperglycaemia, markers of endothelial dysfunction, nitrotyrosine, 8-iso prostaglandin F2alpha, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, interleukin (IL)-6 and IL-18 were increased in all the subgroups. Levels were normalized, at all time points, by treatments A, B and C in the subgroups 1 and 2. In the third subgroup, levels were normalized only by the simultaneous normalization of blood glucose and vitamin C treatment. During treatment D, the levels were improved at 6 h in all the subgroups, but normalized at 12 h only after vitamin C in subgroups 1 and 2, but not in subgroup 3.. This study suggests that different subgroups of Type 1 diabetic patients react identically to acute hyperglycaemia and insulin, but differently to glucose normalization.

Topics: Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Endothelium, Vascular; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Inflammation; Insulin; Male; Oxidative Stress; Young Adult

The objective of the study was to investigate the effect of different periods of hyperglycemia on the reversal of endothelial dysfunction by glucose normalization and antioxidant therapy.. Ten healthy subjects and three subgroups of 10 type 1 diabetic subjects were enrolled as follows: 1) patients within 1 month of diagnosis; 2) patients between 4.5 and 5.2 yr from diagnosis and with glycosylated hemoglobin levels 7% or greater since diagnosis; 3) patients between 4.8 and 5.4 yr from diagnosis and with glycosylated hemoglobin levels greater than 7% since diagnosis. Each patient participated in three experiments: 1) 24-h insulin treatment, achieving a near normalization of glycemia, together with the addition of the antioxidant vitamin C during the last 12 h; 2) 24-h vitamin C treatment with insulin treatment for the last 12 h; and 3) treatment with both vitamin C and insulin for 24 h.. Endothelial function, as measured by flow-mediated vasodilation of the brachial artery and levels of nitrotyrosine, an oxidative stress marker, were normalized by each treatment in subgroups 1 and 2. In the third subgroup, neither glucose normalization nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. Combining insulin and vitamin C, however, normalized endothelial dysfunction and nitrotyrosine.. This study suggests that long-lasting hyperglycemia in type 1 diabetic patients induces long-term alterations in endothelial cells, which may contribute to endothelial dysfunction and is interrupted only by both glucose and oxidative stress normalization.

Topics: Adult; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 1; Endothelium, Vascular; Female; Humans; Hyperglycemia; Insulin; Male; Oxidative Stress

Topics: Animals; Antioxidants; Ascorbic Acid; Critical Care; Endothelium, Vascular; Humans; Hyperglycemia; Mice; Microcirculation; Nitric Oxide Synthase Type III; Oxidative Stress; Sepsis

Nickel-induced hyperglycemia in rats under both acute and subchronic exposure conditions could be due to increased hepatic glycogenolysis, increased pancreatic release of glucagon, decreased peripheral utilization of glucose, or gluconeogenesis. We studied the effect of acute and subchronic nickel sulfate treatment on Wister strain male albino rats simultaneously treated with combined L-ascorbic acid and alpha-tocopherol. The simultaneous treatment with L-ascorbic acid or alpha-tocopherol appears to be beneficial for regulating glucose homeostasis in rats. A significant rise of blood glucose level was also observed with L-ascorbic acid supplementation alone, but not in the case of alpha-tocopherol supplementation alone.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Glucose Tolerance Test; Homeostasis; Hyperglycemia; Liver Glycogen; Male; Nickel; Rats; Rats, Wistar

Hitherto unknown efficacy of the peel extracts of Mangifera indica (MI), Cucumis melo (CM) and Citrullus vulgaris (CV) fruits in ameliorating the diet-induced alterations in dyslipidemia, thyroid dysfunction and diabetes mellitus have been investigated in rats. In one study, out of 4 different doses (50-300 mg/kg), 200 mg/kg of MI and 100 mg/kg for other two peel extracts could inhibit lipidperoxidation (LPO) maximally in liver. In the second experiment rats were maintained on pre-standardized atherogenic diet CCT (supplemented with 4% cholesterol, 1% cholic acid and 0.5% 2-thiouracil) to induce dyslipidemia, hypothyroidism and diabetes mellitus and the effects of the test peel extracts (200 mg/kg of MI and 100 mg/kg for CM and CV for 10 consecutive days) were studied by examining the changes in tissue LPO (in heart, liver and kidney), concentrations of serum lipids, thyroid hormones, insulin and glucose. Rats, treated simultaneously with either of the peel extracts reversed the CCT-diet induced increase in the levels of tissue LPO, serum lipids, glucose, creatinine kinase-MB and decrease in the levels of thyroid hormones and insulin indicating their potential to ameliorate the diet induced alterations in serum lipids, thyroid dysfunctions and hyperglycemia/diabetes mellitus. A phytochemical analysis indicated the presence of a high amount of polyphenols and ascorbic acid in the test peel extracts suggesting that the beneficial effects could be the result of the rich content of polyphenols and ascorbic acid in the studied peels.

Topics: Animals; Ascorbic Acid; Atherosclerosis; Blood Glucose; Citrullus; Creatine Kinase, MB Form; Cucumis melo; Diabetes Mellitus; Diet, Atherogenic; Dyslipidemias; Flavonoids; Fruit; Hyperglycemia; Hypoglycemic Agents; Hypothyroidism; Lipid Peroxidation; Lipids; Mangifera; Phenols; Phytotherapy; Plant Extracts; Polyphenols; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

High-fat diets and oxidative damage may contribute to the development of type 2 diabetes. Hypolipidaemic drugs and antioxidants were supposed to prevent the development of the disease. In this study, we investigated preventive effects of fenofibrate (200 mg kg(-1)), vitamin C (30 mg kg(-1)), combination of both in mice induced by streptozotocin (35 mg kg(-1)) and soluble lard (15 ml kg(-1)). The results showed the mice demonstrated hyperglycaemia and hypercholesterolaemia, visceral fat accumulation, and a slight increase in liver glycogen/triglyceride and oxidative stress within 60 days of treatment. Fenofibrate enhanced insulin sensitivity, improved glycaemic control, lowered serum triglycerides, reduced body and visceral fat weights, and decreased liver glycogen/lipid levels but showed hepatotoxicity in the mice. Vitamin C neither itself prevented nor enhanced preventive effects of fenofibrate on glucose and lipid metabolism but partly attenuated the hepatotoxicity of fenofibrate. These results suggest that fenofibrate inhibit development of type 2 diabetes induced by high-fat diets and oxidative stress. However, here, vitamin C just can serve as an adjunct to fenofibrate therapy against its hepatotoxicity. In the future study, we should investigate if higher dosage of vitamin C or other antioxidants would enhance preventive effects of fenofibrate in type 2 diabetes.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Chemical and Drug Induced Liver Injury; Cholesterol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Fats; Drug Therapy, Combination; Fenofibrate; Glycogen; Hypercholesterolemia; Hyperglycemia; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Intra-Abdominal Fat; Liver; Liver Diseases; Male; Matrix Metalloproteinase 9; Mice; Oxidative Stress; Streptozocin; Triglycerides

Long-lasting hyperglycemia in type 1 diabetic patients induces permanent alterations of endothelial function by increased oxidative stress, even when glycemia is normalized.. In this study, 36 type 1 diabetic patients and 12 control subjects were enrolled. The diabetic patients were divided into three groups. The first group was treated for 24 h with insulin, achieving a near normalization of glycemia. After 12 h of this treatment, vitamin C was added for the remaining 12 h. The second group was treated for 24 h with vitamin C. After 12 h of this treatment, insulin was started, achieving a near normalization of glycemia for the remaining 12 h. The third group was treated for 24 h with both vitamin C and insulin, achieving near normalization of glycemia. The same protocols were performed after 1 month of telmisartan or placebo.. Neither normalization of glycemia nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. Combining insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal levels. Telmisartan significantly improved basal endothelial function and decreased nitrotyrosine plasma levels. In patients treated with telmisartan, a near normalization of both flow-mediated vasodilation and oxidative stress was achieved when glycemia was normalized, whereas adding vitamin C infusion did not show further effect on endothelial function or nitrotyrosine plasma levels.. These data indicate that combining the normalization of glycemia with an antioxidant can normalize endothelial function in type 1 diabetic patients and that telmisartan works as an antioxidant like vitamin C.

Topics: Angiotensin II Type 1 Receptor Blockers; Antioxidants; Ascorbic Acid; Benzimidazoles; Benzoates; Diabetes Mellitus, Type 1; Endothelium, Vascular; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Oxidative Stress; Telmisartan; Vascular Diseases

The current study was aimed to investigate effects of long-term supplementation of vitamin C on the iris microcirculation in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar-Furth rats by intravenous injection of STZ (55 mg/kg b.w.). The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and STZ rats supplemented with vitamin C (STZ-vitC). For supplementation of vitamin C, ascorbic acid (1 g/l) was added into the drinking water. The experiments were performed at different periods (8, 12, 24 and 36 weeks) after injection of STZ. Blood glucose, tissue lipid peroxidation and plasma vitamin C were measured. To examine the endothelial function, leukocyte adhesion to the venular endothelium was evaluated in the iris post-capillaries by means of counting the number of leukocytes labeled with rhodamine 6G. Blood flow perfusion in the iris was monitored using a laser Doppler flow meter. In the STZ rats, hyperglycemia was induced with an increase in HbA(1c) and lipid peroxidation but with a decrease in the plasma vitamin C level which improved by vitamin C supplementation. The number of adherent leukocytes increased significantly, associated with reduction in the iris blood flow perfusion, at 8, 12, 24 and 36 weeks after injection of STZ. In the STZ-vitC rats, the iris blood flow perfusion was significantly increased in comparison with the STZ rats, while the leukocyte adhesion was decreased at 24 and 36 weeks. The statistical analysis shows that the leukocyte adhesion decreased with increase in the iris blood flow perfusion in STZ and STZ-vitC rats. In conclusion, vitamin supplementation suppressed leukocyte adhesion and thus endothelial dysfunction, associated with increase in iris blood flow perfusion in diabetes. The antioxidant vitamin C may be a therapeutic agent for preventing diabetic retinopathy.

Topics: Administration, Oral; Animals; Ascorbic Acid; Blood Glucose; Cell Adhesion; Diabetes Mellitus, Experimental; Endothelium, Vascular; Hyperglycemia; Iris; Laser-Doppler Flowmetry; Lipid Peroxidation; Male; Microcirculation; Rats; Rats, Inbred WF; Regional Blood Flow; Streptozocin; Vitamins; Water Supply

Hyperglycemia worsens outcome of stroke either in the clinical setting or in animal models. In the present study, two focal cerebral ischemia models, permanent middle cerebral artery occlusion (MCAO, 3-4 h) and reversible MCAO (1 h ischemia + 3 h reperfusion), under hyperglycemic conditions were compared. Using 2,3,5-triphenyltetrazolium chloride staining to define viable tissue, this resulted in the infarction area being confined primarily to the cerebral cortex in the permanent MCAO group, while it extended to the subcortical area in the reversible MCAO group, and the lesion areas were respectively 27.7 +/- 5.3% and 46.8 +/- 12.0% of the ipsilateral hemisphere (P = 0.012). Hyperglycemia accelerated the cerebral damage compared to normoglycemia and ascorbic acid pre-treatment maintained tissue viability during the acute phase of hyperglycemic MCAO. In conclusion, hyperglycemia combined with either of the two MCAO models resulted in rapid infarction associated with increased oxidative stress. The hyperglycemic models are suitable for pharmaceutical therapeutic studies of antioxidant efficacy.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Disease Models, Animal; Hyperglycemia; Infarction, Middle Cerebral Artery; Male; Rats; Rats, Sprague-Dawley

Animal and tissue studies have indicated that the carotid bodies are sensitive to glucose concentrations within the physiological range. This glucose sensitivity may modulate the ventilatory response to hypoxia, with hyperglycaemia suppressing the hypoxic response and hypoglycaemia stimulating it. This study was designed to determine whether hypo- and hyperglycaemia modulate the hypoxic ventilatory response in humans. In 11 normal research participants, glucose levels were clamped at 2.8 and 11.2 mmol l(-1) for 30 min. At the start and end of each clamp, blood was drawn for hormone measurement and the isocapnic hypoxic ventilatory response was measured. Because generation of reactive oxygen species may be a common pathway for the interaction between glucose and oxygen levels, the experiments were repeated with and without pretreatment for 1 week with vitamins C and E. Hypoglycaemia caused an increase in the counter-regulatory hormones, a 54% increase in isocapnic ventilation, and a 108% increase in the hypoxic ventilatory response. By contrast, hyperglycaemia resulted in small but significant increases in both ventilation and the hypoxic ventilatory response. Antioxidant vitamin pretreatment altered neither response. In conclusion, the stimulant effect of hypoglycaemia on the hypoxic ventilatory response is consistent with a direct effect on the carotid body, but an indirect effect through the activation of the counter-regulatory response cannot be excluded. The mechanisms behind the mild stimulating effect of hyperglycaemia remain to be elucidated.

Topics: Adult; Antioxidants; Ascorbic Acid; Female; Glucose Clamp Technique; Hormones; Humans; Hyperglycemia; Hypoglycemia; Hypoxia; Male; Respiration; Vitamin E

In this Comment, the ultimate intent is to increase survival of the anticipated global flu pandemic. The apparent failure of "medicine" to provide a completely understood and logically based biochemical prevention and treatment for all influenzas (and many other viral diseases) may be an unavoidable result of the evolving complexity of the H5N1 virus. However, clinical experience cited in all accounts, including the 2003 to 2006 period, suggest that: (i) ascorbic acid is not being administered to humans infected or at risk for influenza, and (ii) ascorbic acid is (mistakenly) believed to be a vitamin ("vitamin C"). Proper use of ascorbic acid as described here could provide effective containment for the flu pandemic.

Topics: Animals; Ascorbic Acid; Communicable Disease Control; Diet; Disease Outbreaks; Humans; Hyperglycemia; Influenza A Virus, H5N1 Subtype; Influenza in Birds; Influenza, Human; Models, Biological; Poultry

This study was designed to determine the effect of diphenyl diselenide and ebselen, synthetic organoselenium compounds with antioxidant properties, in diabetic rats. Diabetes was induced by the administration of streptozotocin (STZ) (45mg/kg, intravenous). In experimental trials, diphenyl diselenide, but not ebselen, caused a significant reduction in blood glucose levels of STZ-treated rats. This effect of diphenyl diselenide was accompanied by a reduction in the levels of glycated proteins. Diphenyl diselenide ameliorate superoxide dismutase activity (liver and erythrocytes) and Vitamin C levels (liver, kidney and blood), which were decreased in STZ-treated rats. In normal rats, diphenyl diselenide caused per se an increase in hepatic, renal and blood GSH levels. Similarly, treatment with diphenyl diselenide restored hepatic and renal GSH levels in STZ-treated rats. TBARS and protein carbonyl levels were not modified by STZ and/or diphenyl diselenide and ebselen treatments. Our findings suggest that diphenyl diselenide can be considered an anti-diabetogenic agent by exhibiting anti-hyperglycemic and antioxidant properties.

Topics: Alanine Transaminase; Aminolevulinic Acid; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Azoles; Benzene Derivatives; Blood Glucose; Diabetes Mellitus, Experimental; Fructosamine; Glutathione; Glycated Hemoglobin; Hyperglycemia; Isoindoles; L-Lactate Dehydrogenase; Liver; Male; Organoselenium Compounds; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Superoxide Dismutase

This study was aimed to evaluate the combined effect of curcumin with vitamin C supplementation on hyperglycemic and dyslipidemia conditions and endothelial cell dysfunction induced in diabetic rats. Wistar Furth rats were used and divided into four groups: control (single injection of 0.9% sterile saline), STZ (streptozotocin, Sigma, 55 mg/kg.BW, i.v.), STZ-vitC (1 g/l ascorbic acid mixed in drinking water), STZ-cur (daily oral treatment of 300 mg/kg.BW curcumin; Cayman Chemical Co., USA), and STZ-cur+vitC (1 g/l ascorbic acid mixed in drinking water and oral treatment of 300 mg/kg.BW curcumin). On 8th week after STZ-injection, the microcirculation in the iris tissue was observed using intravital fluorescence videomicroscopy, and also leukocyte adhesion in the venule was examined for each group. Blood glucose (BG), lipid profiles, glycosylated hemoglobin (HbA1c) were measured in blood samples collected at the end of each experiment. The contents of liver malondialdehyde (MDA) were also quantified for each group. Feeding curcumin (STZ-cur) could decrease BG, HbA1c, dyslipidemia, and MDA significantly, compared to STZ. In cases of feedings curcumin with vitamin C, these results were more effective in all aspects, including leukocyte adhesion. In conclusion, curcumin might increase the effect of vitamin C in protecting the function of endothelial cells through its anti-oxidant with hypoglycemic and hypolipidemic actions.

Topics: Animals; Ascorbic Acid; Blood Glucose; Curcumin; Diabetes Complications; Diabetes Mellitus, Experimental; Dyslipidemias; Endothelium, Vascular; Hyperglycemia; Iris; Laser-Doppler Flowmetry; Leukocyte Rolling; Lipoproteins; Male; Microcirculation; Microscopy, Video; Rats; Rats, Inbred WF

The 22 supersetnd Hohenheim Consensus Workshop took place in at the University of Stuttgart-Hohenheim. The subject of this conference was vitamin C and its role in the treatment of endothelial dysfunction. Scientists, who had published and reviewed scientific and regulatory papers on that topic were invited, among them basic researchers, toxicologists, clinicians and nutritionists. The participants were presented with eleven questions, which were discussed and answered at the workshop, with the aim of summarising the current state of knowledge. The explicatory text accompanying the short answers was produced and agreed on after the conference and was backed up by corresponding references. The therapeutic relevance of administration of the physiological antioxidant vitamin C in high parenteral doses in Endothelial Dependent Pathophysiological Conditions (EDPC) was discussed. Endothelial dysfunction is defined as including disturbed endothelial dependant relaxation of resistance vessels, breakdown of the microvascular endothelial barrier and/or loss of anti-adhesive function. It occurs in severe burn injury, intoxications, acute hyperglycemia, sepsis, trauma, and ischemic-reperfusion tissue injury and is induced by oxidative stress. Reduced plasma ascorbate levels are a hallmark of oxidative stress and occur in severe burns, sepsis, severe trauma, intoxication, chemotherapy/radiotherapy and organ transplantation. Vitamin C directly enhances the activity of nitric oxide synthase, the acyl CoA oxidase system and inhibits the actions of proinflammatory lipids. There is experimental evidence that parenteral high-dose vitamin C restores endothelial function in sepsis. In vitro, supraphysiological concentrations (> 1mM) of ascorbate restore nitric oxide bioavailability and endothelial function. Only parenterally, can enough vitamin C be administered to combat oxidative stress. There is no evidence that parenteral vitamin C exerts prooxidant effects in humans. Theoretical concerns in relation to competitive interactions between vitamin C and glucose cellular uptake are probably only relevant for oxidised vitamin C (dehydroascorbate).

Topics: Acute Disease; Acyl-CoA Oxidase; Ascorbic Acid; Burns; Endothelium, Vascular; Glucose; Heart Failure; Humans; Hyperglycemia; Infusions, Parenteral; Myocardial Ischemia; Nitric Oxide Synthase Type III; Oxidative Stress; Poisoning; Reperfusion Injury; Sepsis

Clinical research has confirmed the efficacy of several photo-chemicals in modulating oxidative stress associated with diabetes mellitus. Here we investigate the effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on antioxidant status in streptozotocin-nicotinamide-induced diabetes in rats. A single dose of streptozotocin (65 mg kg(-1) bwt) resulted in decreased insulin, hyperglycemia, increased lipid peroxidation (thiobarbituric reactive substances, lipid hydroperoxides), and decreased antioxidant levels (vitamin C, vitamin E, reduced glutathione and ceruloplasmin). The oral administration of THC (80 mg kg(-1) bwt) for 45 days to diabetic rats significantly increased plasma insulin and plasma antioxidants and significantly decreased lipid peroxidation. The positive effects of THC were better that those achieved with curcumin. The results of the study indicate that in addition to its antidiabetic effect in type 2 diabetic rats, THC has an antioxidant effect.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Blood Glucose; Ceruloplasmin; Curcumin; Diabetes Mellitus, Experimental; Glutathione; Hyperglycemia; Insulin; Lipid Peroxidation; Male; Niacinamide; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Vitamin E

Observation shows diabetic patients to be more prone to oxidative stress because of hyperglycemia. The elevation of free radical production by this hyperglycemic production may exacerbate cardiovascular complication in diabetes. This study aims to investigate the oxidative stress related parameters in type 2 DM. Since the effects of glycemic control and cardiovascular complications in DM on these parameters has been not fully determined, the comparison between plasma MDA (malondialdehyde) and antioxidant nutrients with their age-matched normal healthy group may be used to determine the susceptibility of oxidative stress in this type of DM.. MDA and antioxidant nutrients (vitamin A, C, E and beta-carotene) were analyzed in plasma of 19 subjects with poorly controlled type 2 DM (fasting plasma glucose [FPG] > 180 mg/dl), 26 subjects with fairly controlled type 2 DM (FPG < or = 180 mg/dl), and 20 subjects with type 2 DM complicated coronary heart disease (CHD) who were matched for age and gender. Twenty healthy subjects with normal plasma glucose level (FPG < 110 mg/dl) and matched for age and gender served as a control group. In all groups of DM these oxidative stress parameters were compared to a normal group.. The plasma MDA levels were significantly higher in all types of DM compared to age-matched normal control. Plasma antioxidant vitamin C and E significantly lower only in poorly controlled and CHD complicated type 2 DM, respectively. The mean of plasma vitamin E level was lowest in type 2 DM complicated with CHD. No significant differences in both plasma vitamin A and beta-carotene were noted between any types of DM and age-matched normal healthy group. The positive correlation between MDA and FPG was demonstrated in most group of patients with their normal subjects except in fairly controlled type 2 DM and negative correlation between vitamin E and FPG was also demonstrated in type 2 DM with CHD.. These findings suggested that diabetic patients were susceptible to oxidative stress and higher plasma glucose level had an association with free radical-mediated lipid peroxidation. The lowest level of vitamin E in type 2 DM complicated with CHD indicated that oxidative stress played an important role in cardiovascular complication and vitamin E supplementation may be necessary for treatment and prevention in this group of diabetics.

Topics: Adult; Aged; Antioxidants; Arteriosclerosis; Ascorbic Acid; Blood Glucose; Case-Control Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Lipid Peroxidation; Male; Middle Aged; Nutritional Status; Oxidative Stress; Risk Factors; Vitamin E

Besides the classical cardiovascular diseases, high levels of blood glucose directly interfere with cardiomyocytes. The mechanisms responsible for this have not yet been explored in detail. This study aims to determine if hyperglycaemia has any impact on prominent signalling molecules and on the contractile function of cardiomyocytes. Freshly isolated cardiomyocytes from adult rats were treated with various concentrations of glucose. Formed free radicals were measured by DCF-fluorescence. TGFbeta expression and p38 MAP-kinase (MAPK) activation were measured by Western blotting. The contractile efficiency was determined by measurement of the maximal amount of cell shortening. Glucose (30 mM) caused an increase in formation of radicals, phosphorylation of p38 MAPK, and TGFbeta expression. Under conditions of low viscosity (1 cp), contractile responses to hyperglycaemia (15 mM) were not altered in contrast to control. However, enhancement of viscosity (400 cp) effected a limitation of contractile function. The responsiveness to beta-adrenoceptor stimulation did not change. Neither inhibition of p38 MAPK with SB 202190 (1 microM) nor inhibition of reactive oxygen species with vitamin C did alter these measured functional parameters. Diabetes mellitus directly influences the activation degree of prominent signalling molecules and the contractile function of adult ventricular cardiomyocytes, which results in facilitating in the development of diabetic cardiomyopathy.

Topics: Animals; Antioxidants; Ascorbic Acid; Cells, Cultured; Diabetes Mellitus; Electrophysiology; Glucose; Hyperglycemia; Imidazoles; Isoproterenol; Male; Muscle Contraction; Myocytes, Cardiac; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Kinase Inhibitors; Pyridines; Rats; Rats, Wistar; Reactive Oxygen Species; Receptors, Adrenergic, beta; Signal Transduction; Transforming Growth Factor beta

Studies on plasma nitrotyrosine (NT) levels, a measure of oxidative injury, in diabetes are limited and discordant; the amount of antioxidants might represent a possible explanation for the discordant results. The aim of this paper is to evaluate the association between plasma NT levels and glucose tolerance status, according to antioxidant vitamin intakes.. In three hundred men randomly selected from a population-based cohort, NT levels were measured and dietary intake assessed by a food-frequency questionnaire. Results NT values were similar in patients with diabetes (n = 34), impaired fasting glucose (n = 77) and normoglycaemic subjects (n = 189). However, in subjects with lower than recommended daily intakes of antioxidant vitamins C and A, NT levels were significantly higher in the diabetic patients. In a multiple regression model, after adjustments for age, body mass index (BMI) and smoking habits, NT levels were significantly associated with fasting glucose in patients with lower intakes of vitamin C (beta = 11.4; 95% CI 1.3-21.5) and vitamin A (beta = 14.9; 95% CI 3.9-25.9), but not in subjects with lower intake of vitamin E.. A significant positive correlation between NT levels and fasting glucose is evident only in the presence of a reduced intake of some antioxidant vitamins. These findings might explain, at least in part, the discrepant results of previous studies and, if confirmed by further studies, suggest a simple measure (a balanced diet) to alleviate the increased oxidative stress of diabetes.

Topics: Age Factors; Antioxidants; Ascorbic Acid; Blood Glucose; Body Mass Index; Cohort Studies; Diabetes Mellitus; Diet; Humans; Hyperglycemia; Male; Middle Aged; Smoking; Tyrosine; Vitamin A; Vitamin E; Vitamins

The onset of complications in Type 2 diabetes mellitus (DM) patients cannot be predicted in individuals. Evidence suggests a link between complications and hyperglycaemia, oxidative stress and antioxidants, but causality is unclear. This study investigated baseline (entry) fasting plasma ascorbic acid, lymphocytic DNA damage and glycaemic control in Type 2 DM as part of a long-term study, the aim of which is to explore a biomarker profiling approach to identify and improve outcome in high-risk subjects.. A cross-sectional study, in which DNA damage, glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and ascorbic acid (AA) were measured on fasting blood samples collected from 427 Type 2 DM subjects.. DNA damage was significantly (P < 0.0001) and directly correlated to both FPG (r = 0.540) and HbA(1c) (r = 0.282), and was significantly (P < 0.0001), independently and inversely correlated to plasma AA (r = -0.449). In those subjects with both poor glycaemic control and low AA (< 48 microm, the overall mean value for the study group), DNA damage was significantly (P < 0.005) higher compared with those subjects with a similar degree of hyperglycaemia but with AA above the mean.. The novel finding of a significant inverse relationship between plasma AA and DNA damage in Type 2 DM indicates that poorly controlled diabetic subjects might benefit from increased dietary vitamin C. The data also have important implications for biomarker profiling to identify those subjects who might benefit most from intensive therapy. Longer-term follow-up is underway.

Topics: Ascorbic Acid; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; DNA Damage; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Middle Aged; Oxidative Stress

The purpose of this study was to investigate the effect of regular meals on the daily profile of blood oxidative stress markers in type 2 diabetic patients with postprandial hyperglycaemia. %CoQ10, calculated as the ratio of ubiquinone-10 (oxidised form of coenzyme Q10) to ubiquinol-10 (reduced form), was used as a sensitive marker of oxidative stress. Blood samples were collected from patients before and 2 h after breakfast, lunch and supper, and at 10 p.m. Patients were selected for the study if their blood glucose levels were <7 mmol/l before breakfast and > or =11.1 mmol/l on at least one occasion after breakfast. %CoQ10 levels after breakfast and throughout the day were significantly higher than those before breakfast (p=0.006-0.04). In contrast to the wave-like changes in plasma glucose levels, %CoQ10 levels increased after breakfast and remained at high levels throughout the day. These results indicated that diabetic patients with postprandial hyperglycaemia were exposed to meal-induced periods of oxidative stress during the day. Postprandial hyperglycaemia therefore has the potential to increase the risk of atherosclerotic cardiovascular disease through induction of oxidative stress.

Topics: Ascorbic Acid; Biomarkers; Blood Glucose; Coenzymes; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Oxidative Stress; Patient Selection; Postprandial Period; Ubiquinone; Vitamin E

Metabolomics, or metabolic profiling, is an emerging discipline geared to providing information on a large number of metabolites, as a complement to genomics and proteomics. In the current study, a fluorine-labeled derivative of ascorbic acid (F-ASA), a major antioxidant- and UV-trapping molecule in the aqueous humor and the lens, was used to investigate the extent to which the lens accumulates potentially toxic degradation products of vitamin C.. Human lens epithelial cells (HLE-B3) and rat lenses were exposed to hyperglycemic or oxidative stress in vitro or in vivo and probed for accumulation of F-ASA, fluoro-dehydroascorbate (F-DHA), fluoro-2,3-diketogulonate (F-DKG), and their degradation products in protein-free extracts, by proton-decoupled 750-MHz (19)F-nuclear magnetic resonance (NMR) spectroscopy.. F-ASA and F-DHA were taken up into HLE B-3 cells by an Na(+)-dependent transporter. Their uptake was unexpectedly only slightly affected by hyperglycemia in vitro, unless glutathione was severely depleted. Glycemic stress catalyzed oxidation of F-ASA into a single novel F-compound at -212.4 ppm, whereas F-DHA and F-DKG were the major degradation products observed after GSH depletion. In contrast, F-ASA uptake was markedly suppressed in diabetic cataractous rat lenses, which accumulated both the F-DHA and the -212.4-ppm compound. In an unexpected finding, the latter formed only from F-ASA and not F-DHA or F-DKG, suggesting a novel pathway of in vivo F-ASA degradation. Both the cells and the intact rat and human lenses were permeable to several advanced F-ASA and F-DHA degradation products, except F-DKG. The unknown compound at -212.4 ppm was the only F-ASA degradation product that spontaneously formed in rabbit aqueous humor upon incubation with F-ASA.. These studies suggest the existence of a novel ascorbic-acid-degradation pathway in the lens and aqueous humor that is influenced by the nature of the oxidant stress. Under similar culture conditions, intact lenses are more prone to hyperglycemia-mediated oxidant stress than are lens epithelial cells, but both are permeable to various F-ASA degradation products, the structure and biological roles of which remain to be established.

Topics: 2,3-Diketogulonic Acid; Adult; Aged; Animals; Ascorbic Acid; Biological Transport; Buthionine Sulfoximine; Cataract; Cell Culture Techniques; Cytochalasin B; Dehydroascorbic Acid; Enzyme Inhibitors; Epithelial Cells; Fluorine Radioisotopes; Galactose; Glucose; Glutathione; Humans; Hyperglycemia; Lens, Crystalline; Magnetic Resonance Spectroscopy; Male; Middle Aged; Organ Culture Techniques; Oxidative Stress; Rabbits; Rats; Rats, Sprague-Dawley

The metabolic peturbations of diabetes cause functional and structural changes in the retinal microvasculature which are termed diabetic retinopathy. Exposure of the eye to ionising radiation results in retinal vascular damage with a clinical manifestation known as radiation retinopathy. Anecdotal studies have suggested that exposure to even low levels of ionising radiation may accelerate development of pathological changes in the retinal vessels of patients with diabetes. This in vitro study was designed to test the hypothesis that the combination of a high ambient glucose environment (mimicking hyperglycaemia and diabetes) along with exposure to ionising radiation would result in more accentuated damage to cultured retinal vascular cells.. Retinal microvascular endothelial cells and pericytes were propagated for 5 days in either 5 mM (euglycaemia) or 15 mM (hyperglycaemia) glucose. Cells were irradiated with 250, 500 or 1000 cGy of ionising radiation using a 6 MV beam photon accelerator which was used for radiotherapy. Similarly treated but unirradiated cells were used as controls. DNA damage was assessed using the single-cell gel electrophoresis (comet) assay.. Unirradiated control cells pre-exposed to glucose at either 5 mM or 15 mM for 5 days showed no significant difference in mean percentage tail DNA representing damage. However, in both pericytes and endothelial cells exposed to ionising radiation, cells cultured in 15 mM glucose showed significantly higher levels of DNA damage compared with those cultured in 5 mM glucose, with maximal differences being seen at the higher radiation doses (500 and 1000 cGy).. This study has demonstrated that retinal microvascular cells cultured in high glucose express more DNA damage when exposed ionising radiation. These findings have important implications for the management of patients with diabetes if they require radiotherapy for neoplastic disease.

Topics: Animals; Ascorbic Acid; Cattle; Cells, Cultured; Comet Assay; DNA Damage; Endothelium, Vascular; Glucose; Hyperglycemia; Pericytes; Radiation Tolerance; Radiation, Ionizing; Retinal Vessels; Tocopherols

S-nitrosoglutathione (GSNO) and S-nitroso-N-acetlypenicillamine (SNAP) are two of the most common sources of nitric oxide (NO) in the biomedical field. Vitamin C has been known to accelerate the decomposition of GSNO and SNAP increasing the release and availability of NO which is cytotoxic at non-physiological concentrations. The study investigates any potential detrimental effect of vitamin C and GSNO, vitamin C and SNAP on glucose metabolism in normotensive and normoglycemic dogs.. The results showed that administration of vitamin C (50 mg/kg) and GSNO (35 mg/kg & 50 mg/kg), or vitamin C (50 mg/kg) and SNAP (10 mg/kg) to overnight fasted dogs resulted in significant elevation of the blood glucose levels, attaining maximum level at the 2.0 or 2.5 h time point postprandially. The elevated blood glucose levels were due to significant reduction in plasma insulin levels in the dogs treated with vitamin C and GSNO, or vitamin C and SNAP (P < 0.05). The decreased insulin response was associated with significant elevation of nitric oxide produced from GSNO and SNAP co-administered with vitamin C, as assessed by plasma nitrate/nitrite levels.. The results indicate that enhanced NO release by vitamin C affects postprandial blood glucose and plasma insulin levels and the reduced glucose tolerance is mainly due to impaired insulin release. The clinical relevance of the findings of this study suggest that hypertensive diabetic patients treated with GSNO or SNAP, who are on vitamin C supplements may be more predisposed to further decrease in their glycemic control.

Topics: Animals; Ascorbic Acid; Blood Glucose; Dogs; Drug Synergism; Female; Hyperglycemia; Male; Models, Animal; S-Nitroso-N-Acetylpenicillamine; S-Nitrosoglutathione; Vasodilator Agents

The effects of dietary vitamin C supplementation on glucose homeostasis and insulin glycation were examined in adult lean and obese hyperglycemic (ob/ob) mice. In lean mice, supplementation of the drinking water with vitamin C (25 g/L) for 14 days did not affect food intake, fluid intake, glycated hemoglobin, plasma glucose, or plasma insulin concentrations. Total pancreatic insulin content and the percentage of glycated pancreatic insulin were also similar to control lean mice. In ob/ob mice, vitamin C supplementation caused significant reductions by 26% to 48% in food intake and fluid intake, glycated hemoglobin, plasma glucose, and insulin concentrations compared with untreated control ob/ob mice. The total insulin content and the extent of insulin glycation in the pancreas of ob/ob mice were also significantly decreased by 42% to 45% after vitamin C supplementation. This change was accompanied by a significant 80% decrease in the percentage of glycated insulin in the circulation of vitamin C-supplemented ob/ob mice. These data demonstrate that vitamin C supplementation can decrease insulin glycation and ameliorate aspects of the obesity-diabetes syndrome in ob/ob mice.

Topics: Animals; Ascorbic Acid; Blood Glucose; Body Weight; Dietary Supplements; Drinking Behavior; Energy Intake; Glycated Hemoglobin; Homeostasis; Hyperglycemia; Insulin; Insulin Secretion; Mice; Mice, Obese; Obesity; Reference Values

To examine the cross-sectional association between plasma vitamin C, self-reported diabetes, and HbA1c.. Data from a population-based study of diet, cancer, and chronic disease were analyzed. A total of 2,898 men and 3,560 women 45-74 years of age who were registered with general practices in Norfolk, U.K., were recruited to the European Prospective Investigation Into Cancer-Norfolk study between 1995 and 1998.. Mean plasma vitamin C levels were significantly higher in individuals with HbA1c levels < 7% than in those with self-reported diabetes or prevalent undiagnosed hyperglycemia (HbA1c > or = 7%). An inverse gradient of mean plasma vitamin C was found in both sexes across quintiles of HbA1c distribution < 7%. The odds ratio (95% CI) of having prevalent undiagnosed hyperglycemia per 20 micromol/l (or 1 SD) increase in plasma vitamin C was 0.70 (0.52-0.95) (adjusted for sex, age, BMI, waist-to-hip ratio, tertiary education, any use of dietary supplements, vegetarian diet, alcohol consumption, physical activity, dietary vitamin E, dietary fiber, dietary saturated fat, and smoking history). The unadjusted change in HbA1c per 20 micromol/l increase in vitamin C estimated by linear regression was -0.12% (-0.14 to -0.09) in men and -0.09% (-0.11 to -0.07) in women. After adjusting for the possible confounders, these values were -0.08% (-0.11 to -0.04) in men and -0.05% (-0.07 to -0.03) in women.. An inverse association was found between plasma vitamin C and HbA1c. Dietary measures to increase plasma vitamin C may be an important public health strategy for reducing the prevalence of diabetes.

Topics: Aged; Ascorbic Acid; Chronic Disease; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Diet; England; Europe; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Middle Aged; Neoplasms; Odds Ratio; Prevalence

Topics: Ascorbic Acid; Blood Glucose; Diagnosis, Differential; Dietary Supplements; Humans; Hyperglycemia; Male; Middle Aged

The present study investigates the pharmacological activity of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) on the plasma glucose and insulin levels in healthy normoglycemic dogs. The plasma nitrate and nitrite concentrations were measured by a commercial autoanalyzer and taken as the biochemical markers of in vivo nitric oxide formation. Plasma glucose levels were measured by the glucose oxidase method, while the insulin levels were determined by radioimmunoassay. The possible effect of the coadministration of ascorbic acid (vitamin C) and GSNO on plasma glucose levels was also examined. In healthy normoglycemic dogs, administration of 35 and 50 mg/kg of GSNO caused a dose-dependent increase in postprandial plasma glucose levels. The plasma glucose levels were significantly elevated at the 1.5-, 2.0-, and 2.5-h time intervals of the oral glucose tolerance test at both concentrations of GSNO (P < 0.05). These values were significantly higher than those obtained using captopril (control). Furthermore, coadministration of 35 mg/kg of GSNO and 50 mg/kg ascorbic acid enhanced the postprandial hyperglycaemic effect observed for the administration of only 35 mg/kg of GSNO. There was a 35-100% increase in plasma nitrate concentration on administration of both doses of GSNO. Intravenous administration of GSNO (35 mg/kg) and captopril (20 mg/kg) significantly decreased the mean arterial blood pressure and increased the heart rate. The blood pressure-lowering effect of these drugs was more pronounced on systolic than on diastolic blood pressure (P < 0.05). These results suggests that in healthy normoglycaemic dogs: (a) nitric oxide released from GSNO increases postprandial plasma glucose levels and inhibits glucose-stimulated insulin secretion, (b) ascorbic acid enhances the postprandial hyperglycaemic effect of GSNO, probably by increasing the release of NO, and (c) GSNO decreases mean arterial blood pressure and increase heart rate in normotensive dogs.

Topics: Animals; Ascorbic Acid; Blood Glucose; Blood Pressure; Captopril; Dogs; Female; Glutathione; Heart Rate; Hemodynamics; Hyperglycemia; Insulin; Male; Nitric Oxide Donors; Nitroso Compounds; Postprandial Period; Radioimmunoassay; S-Nitrosoglutathione

Chronic production of reactive oxygen species (ROS) and/or deficiency in the antioxidant defense system are observed in non-insulin-dependent diabetes mellitus (NIDDM) patients. As an adjunct to the usual indirect parameters for evaluating oxidative stress, we assessed the feasibility of oxyradicals detection in venous blood by electron spin resonance spectroscopy (ESR). Detection of the ascorbate pool was also performed using the validated ESR analysis of the ascorbyl free radial (AFR)-dimethyl sulfoxide (DMSO) complex.. Plasma lipoperoxidation was characterized by higher levels of total MDA (1.50 +/- 0.08 nmol/L), lower levels of GSH (0.54 +/- 0.02 mmol/L) and of vitamin A (2.13 +/- 0.52 mumol/L) in the NIDDM group than in the controls (0.75 +/- 0.05 nmol/L, 0.90 +/- 0.05 mmol/L, 3.52 +/- 1.04 mumol/L, respectively). Improvement of the ESR measurement of oxyradical adducts has been previously obtained by addition of a new sensitive nitrone (DEPMPO), which acts as a spin-trap. However, in our experiment the ESR signal-to-noise ratio was too low to detect significative oxyradicals adducts in total venous blood of NIDDM patients having a weak production of ROS. A significant difference (p < 0.002) was observed in DMSO/AFR index between controls (24.00 +/- 4.10 nmol/L) and NIDDM patients (7.28 +/- 2.36 nmol/L) suggesting ascorbate depletion related to the free radical production.. The DMSO/AFR index could be an interesting additional marker of oxidative stress during a chronic production of ROS.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Diabetes Mellitus, Type 2; Dimethyl Sulfoxide; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Glutathione; Humans; Hyperglycemia; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Spin Trapping; Vitamins

Latent scurvy is characterized by a reversible atherosclerosis that closely resembles the clinical form of this disease. Acute scurvy is characterized by microvascular complications such as widespread capillary hemorrhaging. Vitamin C (ascorbate) is required for the synthesis of collagen, the protein most critical in the maintenance of vascular integrity. We suggest that in latent scurvy, large blood vessels use modified LDL--in particular lipoprotein(a)--in addition to collagen to maintain macrovascular integrity. By this mechanism, collagen is spared for the maintenance of capillaries, the sites of gas and nutrient exchange. The foam-cell phenotype of atherosclerosis is identified as a mesenchymal genetic program, regulated by the availability of ascorbate. When vitamin C is limited, foam cells develop and induce oxidative modification of LDL, thereby stabilizing large blood vessels via the deposition of LDL. The structural similarity between vitamin C and glucose suggests that hyperglycemia will inhibit cellular uptake of ascorbate, inducing local vitamin C deficiency.

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Collagen; Diabetes Complications; Diabetes Mellitus; Foam Cells; Humans; Hyperglycemia; Lipoprotein(a); Metaplasia; Models, Biological; Scurvy

Sorbitol formation in rat lenses incubated with high levels of glucose was related to activation of aldose reductase (AR). The hyperglycaemia-activated aldose reductase was inhibited by alpha-lipoic (thioctic) acid, O-phenanthroline and aldose reductase inhibitors (ARIs) including Zeopolastat (ZPLS), Sorbinil (SBN) and AL-1576. This study also examined ARIs for the ability to chelate metal ions. We found that ARIs suppress copper-dependent ascorbate oxidation, lipid peroxidation and hydrogen peroxide production in erythrocytes. ARIs also increased partition of copper ions into noctanol, which indicates formation of lipophilic complexes. Our data support the hypothesis that transition metals may be involved in activation of the polyol (aldose reductase) pathway. Also, ARIs function as metal-chelating antioxidants that may contribute to their therapeutic role for diabetic complications.

Topics: 1-Octanol; Aldehyde Reductase; Animals; Ascorbic Acid; Chelating Agents; Copper; Enzyme Activation; Enzyme Inhibitors; Erythrocytes; Fluorenes; Glucose; Humans; Hydantoins; Hydrogen Peroxide; Hyperglycemia; Imidazoles; Imidazolidines; In Vitro Techniques; Ions; Lens, Crystalline; Lipid Peroxidation; NADP; Octanols; Oxidation-Reduction; Phenanthrolines; Rats; Thioctic Acid

It has been suggested earlier that the local deficiency of ascorbic acid in tissues could be responsible for development of various angiopathies in diabetes. Hyperglycemia is one of the factors which could contribute considerably to the development of local ascorbic acid deficiency. Therefore, the effect of glucose on uptake of L-[1-14C] ascorbic acid by fibroblasts was studied in vitro. The data clearly show that ascorbic acid uptake is inhibited instantly by glucose in a concentration dependent fashion. The results support the contention that local ascorbic acid deficiency in tissues could be a natural consequence of hyperglycemia of whatever cause. The rate of ascorbic acid uptake under various conditions suggests that additional supplements of ascorbic acid might be helpful to individuals in averting deleterious effects of hyperglycemia on tissue ascorbic acid supply.

Topics: Animals; Ascorbic Acid; Biological Transport; Cells, Cultured; Diabetes Mellitus; Fibroblasts; Glucose; Humans; Hyperglycemia; Mice; Skin

It has recently been reported that glucose and its analogues inhibit in vitro ascorbic acid transport across the cell membrane of polymorphonuclear leukocytes and fibroblasts. We have studied the effect of in vivo hyperglycemia on the intracellular ascorbic acid level of mononuclear leukocytes in normal and diabetic human subjects. Administration of an intravenous glucose load resulted in a prompt decrease of mononuclear leukocyte ascorbic acid level in the normal subjects. The rate of its decline correlated closely with the rate of change of plasma glucose. Among the NIDDM subjects in the fasting state, the plasma glucose was high and the leukocyte ascorbic acid level was low when compared with that of the normal subjects. The decrease in the leukocyte ascorbic acid level during disposition of the i.v. glucose load was not statistically significant in the diabetics. The hyperglycemia-induced intracellular depletion of ascorbic acid could be clinically important and requires further evaluation.

Topics: Adult; Aged; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Monocytes

To investigate the diabetogenic effect of pure dehydroascorbic acid, male Wister- and Sprague-Dawley rats received i.v. injections of the substance. No hyperglycemia and no decreased glucose tolerance were found. I.v. administration of the hydrolysis products of dehydroascorbic acid and of a solution containing monodehydroascorbate likewise did not increase blood glucose values. It is concluded that in previously performed experiments not dehydroascorbic acid itself but one or several impurities might have produced hyperglycemia in the rat. The electron transfer proteins tested (ascorbate:ferricytochrome b5 oxidoreductase, cytochrome b5, NADH:ferricytochrome b5 oxidoreductase, NADH:monodehydroascorbate oxidoreductase), which might participate in the reduction of dehydroascorbic acid, could not be induced in liver microsomes from Wistar rats by the injection of dehydroascorbic acid, its hydrolysis products, or monodehydroascorbate.

Topics: Animals; Ascorbic Acid; Blood Glucose; Dehydroascorbic Acid; Diabetes Mellitus, Experimental; Electron Transport; Hyperglycemia; Male; Microsomes, Liver; Oxidation-Reduction; Rats; Rats, Inbred Strains

Topics: Animals; Ascorbic Acid; Dehydroascorbic Acid; Erythrocytes; Glucose Tolerance Test; Glucosephosphate Dehydrogenase; Glutathione; Guinea Pigs; Hyperglycemia; Plasma

Topics: Animals; Ascorbic Acid; Biological Transport; Blood Glucose; Female; Guinea Pigs; Hyperglycemia; Maternal-Fetal Exchange; Placenta; Pregnancy; Pregnancy Complications

Topics: Acidosis; Ascorbic Acid; Blood; Cholesterol; Gastrointestinal Diseases; Glycosuria; Humans; Hydrogen-Ion Concentration; Hyperglycemia; Kidney Calculi; Oxalates; Prothrombin; Vitamin B 12

Topics: Animals; Antidepressive Agents; Antithyroid Agents; Ascorbic Acid; Basal Metabolism; Blood Glucose; Body Temperature; Body Temperature Regulation; Dinitrophenols; Glucose; Hyperglycemia; Hypoglycemic Agents; Hypothermia, Induced; Insulin; Liver Glycogen; Motor Activity; Oxygen Consumption; Rats; Time Factors; Tranquilizing Agents

Topics: Ascorbic Acid; Atrophy; Body Temperature Regulation; Burns; Fractures, Bone; Glycosuria; Humans; Hyperglycemia; Muscle Proteins; Nutritional Physiological Phenomena; Proteins; Wounds and Injuries

Topics: Age Factors; Alveolar Process; Ascorbic Acid; Avitaminosis; Blood Proteins; Bone Resorption; Glycosuria; Humans; Hyperglycemia; Hypoglycemia; Oral Health; Toothbrushing

Topics: Animals; Ascorbic Acid; Blood Glucose; Histamine; Histamine H1 Antagonists; Humans; Hyperglycemia; Rabbits

Topics: Animals; Ascorbic Acid; Glycogen; Guinea Pigs; Hyperglycemia; Liver Glycogen; Muscles; Rats; Research; Vitamins

Topics: Ascorbic Acid; Epinephrine; Hyperglycemia; Vitamins

Topics: Animals; Ascorbic Acid; Dehydroascorbic Acid; Hyperglycemia; Injections; Rats; Vitamins