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

The protective effect of onion against oxidative stress in streptozotosin-induced diabetic rats was investigated in comparison with that of quercetin aglycone. We measured oxidative stress biomarkers involving the susceptibility of the plasma against copper ion-induced lipid peroxidation, which was estimated by the amounts of thiobarbituric acid-reactive substances (TBARS) and cholesteryl ester hydroperoxides, and urine TBARS and 8-hydroxydeoxyguanosine contents. After the 12-week feeding period, plasma glucose levels and these biomarkers increased in diabetic rats compared to normal rats. In diabetic rats fed a 6.0% onion diet (quercetin equivalent: 0.023%), quercetin metabolites accumulated in the plasma at concentrations of approximately 35 microM. Onion intake decreased plasma glucose levels and lowered the oxidative stress biomarkers. On the other hand, quercetin metabolites in the plasma of rats fed a diet with 0.023% quercetin aglycone were found at lower concentrations (14.2 microM) than the rats fed the onion diet. Furthermore, oxidative stress biomarkers were higher in the quercetin diet group compared to the onion diet group. These results strongly suggest that onion intake suppresses diabetes-induced oxidative stress more effectively than the intake of the same amount of quercetin aglycone alone.
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PMID:Lowering effects of onion intake on oxidative stress biomarkers in streptozotocin-induced diabetic rats. 1818 15

Oxidative stress plays an important role in aging and various diseases such as cancer, cardiovascular diseases, diabetes mellitus and bronchial asthma. However, little is known about a potential role of oxidative stress in the pathogenesis of severe motor and intellectual disabilities (SMID) in terms of respiratory disturbance, which is the most common complication. In the present study, we examined the urinary levels of oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG), hexanoyl-lysine adduct (HEL) and acrolein-lysine adduct (ACR) in patients with SMID. The mean level of urinary 8-OHdG in SMID patients was significantly higher than that in normal controls (18.8 +/- 9.0 ng/mg Cre and 10.5 +/- 2.9 ng/mg Cre, respectively) (p < 0.01). There was no significant difference of the mean level of urinary HEL between patients with SMID and normal controls (81.9 +/- 40.3 pmol/mg Cre and 69.2 + /-37.7 pmol/mg Cre, respectively), while the mean level of ACR in patients with SMID was higher than that of normal controls (220.5 +/- 118.6 nmol/mg Cre and 144.9 +/- 62.0 nmol/mg Cre, respectively) (p < 0.05). In addition, the level of 8-OHdG was strongly correlated with the severity of respiratory disturbance evaluated as the respiratory disturbance score (RDS) (Spearman r = 0.73, n = 14, p < 0.01). In contrast, there was no correlation between the levels of these oxidative stress markers and age or medication of antiepileptic drugs. These results suggest that urinary 8-OHdG is a potentially useful biomarker for evaluating the severity of respiratory failure in patients with SMID.
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PMID:Oxidative stress as a biomarker of respiratory disturbance in patients with severe motor and intellectual disabilities. 1828 73

The effects of diabetes mellitus on male reproductive health have not been clearly defined. A previous publication from this group reported significantly higher levels of nuclear DNA fragmentation and mitochondrial DNA deletions in spermatozoa from men with type 1 diabetes. This study compared semen profiles, sperm DNA fragmentation and levels of oxidative DNA modification in spermatozoa of diabetic and non-diabetic men. Semen samples from 12 non-diabetic, fertile men and 11 type 1 diabetics were obtained and subjected to conventional light microscopic semen analysis. Nuclear DNA fragmentation was assessed using an alkaline Comet assay and concentrations of 7,8-dihydro-8-oxo-2-deoxyguanosine (8-OHdG), an oxidative adduct of the purine guanosine, were assessed by high-performance liquid chromatography. Conventional semen profiles were similar in both groups, whilst spermatozoa from type 1 diabetics showed significantly higher levels of DNA fragmentation (44% versus 27%; P < 0.05) and concentrations of 8-OHdG (3.6 versus 2.0 molecules of 8-OHdG per 10(5) molecules of deoxyguanosine; P < 0.05). Furthermore, a positive correlation was observed between DNA fragmentation and concentrations of 8-OHdG per 10(5) molecules of deoxyguanosine (rs = 0.7, P < 0.05). The genomic damage evident in spermatozoa of type 1 diabetics may have important implications for their fertility and the outcome of pregnancies fathered by these individuals.
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PMID:Increased concentrations of the oxidative DNA adduct 7,8-dihydro-8-oxo-2-deoxyguanosine in the germ-line of men with type 1 diabetes. 1833 65

This study examined whether oxidative DNA damage and its repair system contribute to the occurrence of diabetes in an experimental rat model. The changed morphological findings of the 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxoG-DNA glycosylase (OGG1) were examined in the pancreatic islets in streptozotocin-induced diabetic rats (60 mg/kg, i.p.). The patterns of immunolocalization were mainly observed in the periphery of the normal pancreatic islet: 8-OHdG in the nucleus and OGG1 in the cytoplasm. The altered immunolocalization of 8-OHdG and OGG1 were greatest in the first hours after streptozotocin injection, and then declined in parallel with the morphological observations of pancreatic beta cell destruction. These results suggested that increased oxidative DNA damage might play a role as the inducer of diabetes and that OGG1 may not successfully mediate DNA repair in streptozotocin-induced diabetic rat pancreas.
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PMID:Immunolocalization of 8-OHdG and OGG1 in pancreatic islets of streptozotocin-induced diabetic rats. 1867 9

Oxidative stress has been postulated to be involved in the development of diabetic nephropathy. In the present study, we evaluated the effect of taurine, an endogenous antioxidant, on diabetic nephropathy by mixing it with the daily drinking water (1%w/v) of streptozotocin-induced diabetic rats from the beginning of the fourth month after the induction of diabetes, during which the urinary protein excretion in untreated diabetic rats showed significant increase in comparison with nondiabetic rats. The taurine administration significantly suppressed further increase in urinary protein excretion in diabetic rats, accompanied by the reduction of mesangial extracellular matrix expansion and TGF-beta expression in the renal glomerulus. Immunohistochemical study showed that taurine administration suppressed the intensified stainings to the three different types of oxidative stress markers, such as 8-hydroxyl-2'-deoxyguanosine (8-OHdG), pentosidine, and nitrotyrosine observed in the renal tissues of untreated diabetic rats. These findings suggest that taurine has the ability to suppress the progression of diabetic nephropathy at least in part by its antioxidant property. Since this beneficial effect of taurine was obtained even if its administration was started after the time point when urinary protein excretion already became apparently higher than that of age-matched nondiabetic animals, taurine administration was potentially expected to be applied in clinical field to retard the development of nephropathy in diagnosed diabetic patients.
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PMID:Taurine administration after appearance of proteinuria retards progression of diabetic nephropathy in rats. 1877 7

Flavonoids are a class of secondary metabolites abundantly found in fruits and vegetables. In addition, flavonoids have been reported as potent antioxidants with beneficial effects against oxidative stress-related diseases such as cancer, aging, and diabetes. The present study was carried out to investigate the cytoprotective effects of morin (2',3,4',5,7-pentahydroxyflavone), a member of the flavonoid group, against hydrogen peroxide (H(2)O(2))-induced DNA and lipid damage. Morin was found to prevent the cellular DNA damage induced by H(2)O(2) treatment, which is shown by the inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation (a modified form of DNA base), inhibition of comet tail (a form of DNA strand breakage), and decrease of nuclear phospho histone H2A.X expression (a marker for DNA strand breakage). In addition, morin inhibited membrane lipid peroxidation, which is detected by inhibition of thiobarbituric acid reactive substance (TBARS) formation. Morin was found to scavenge the intracellular reactive oxygen species (ROS) generated by H(2)O(2) treatment in cells, which is detected by a spectrofluorometer, flow cytometry, and confocal microscopy after staining of 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA). Morin also induces an increase in the activity of catalase and protein expression. The results of this study suggest that morin protects cells from H(2)O(2)-induced damage by inhibiting ROS generation and by inducing catalase activation.
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PMID:Cellular protection of morin against the oxidative stress induced by hydrogen peroxide. 1879 23

Large, prospective, clinical trials have confirmed the efficacy of intensive blood-glucose control to prevent the onset and progression of diabetic complications. However, since it is difficult to maintain blood glucose concentrations close to the normal range, the effect of intensive therapy to prevent diabetic complications may be limited. Other approaches are therefore required to prevent the progression of diabetic complications based on the elucidation of the biological mechanisms. In this review, the impacts of mitochondrial reactive oxygen species (ROS) on diabetes-related complications are described. In endothelial cells, high glucose levels increase mitochondrial ROS, and the normalization of mitochondrial ROS production by inhibitors of mitochondrial metabolism, or by the overexpression of UCP-1 or MnSOD, prevents the glucose-induced accumulation of sorbitol, activation of protein kinase C, and formation of advanced glycation end products, all of which are believed to be major molecular mechanisms of diabetic complications. We also demonstrated that 8-hydroxydeoxyguanosine, which represents mitochondrial oxidative damage, was elevated in patients with either retinopathy, albuminuria, or the increased intima-media thickness of carotid arteries compared to patients without diabetic vascular complications. In addition, to investigate the impact of mitochondrial ROS on diabetic retinopathy in vivo, we established a novel transgenic mouse, which specifically expressed MnSOD in endothelial cells. By the introduction of diabetes, levels of urinary 8-hydroxydeoxyguanosine and expressions of VEGF and fibronectin mRNA in retinas were increased in wild type littermates; however, these observations were ameliorated in transgenic mice. Taking the results together, hyperglycemia could induce mitochondrial ROS production, associating it with the pathogenesis of diabetic vascular complications.
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PMID:[Investigation of a novel mechanism of diabetic complications: impacts of mitochondrial reactive oxygen species]. 1880 Jun 28

Arsenic (As) is an ubiquitous element in the environment for which the main route of human exposure is through consumption of drinking water. Reactive oxygen species generation (ROS) associated with As exposure is known to play a fundamental role in the induction of adverse health effects and disease (cancer, diabetes, hypertension, and cardiovascular and neurological diseases). However, the precise mechanisms of oxidative stress and damage from As exposure are not fully understood and moreover the use of non-invasive methods of measuring ROS generation and oxidative damage footprints in humans is no easy task. Although As induces adverse health effects not all exposed individuals develop degenerative chronic diseases or even manifest adverse effects or symptoms, suggesting that genetic susceptibility is an important factor involved in the human response to As exposure. This mini-review summarizes the literature describing the molecular mechanisms affected by As, as well as the most used biomarkers of oxidative stress and damage in human populations. The most reported biomarkers of oxidative DNA damage are the urinary excretion of 8-OHdG and the comet assay in lymphocytes, and more recently DNA repair mechanism markers from the base and nuclear excision repair pathways (BER and NER). Genetic heterogeneity in the oxidative stress pathways involved in As metabolism are important causative factors of disease. Thus further refinement of human exposure assessment is needed to reinforce study design to evaluate exposure-response relationships and study gene-environment interactions. The use of microarray-based gene expression analysis can provide better insights of the underlying mechanisms involved in As-induced diseases and could help to identify target genes that can be modulated to prevent disease.
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PMID:Biomarkers of oxidative stress and damage in human populations exposed to arsenic. 1898 63

Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.
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PMID:Additional renoprotective effects of azelnidipine combined with angiotensin receptor blockers in patients with diabetic nephropathy. 1900 May 38

Green tea (GT), through its antioxidant properties, may be useful to treat or prevent human diseases. Because several lines of evidence suggest that oxidative stress contributes to the pathogenesis of diabetic nephropathy, we tested the hypothesis that GT prevents diabetes and hypertension-related renal oxidative stress, attenuating renal injury. Spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes and nondiabetic SHR were treated daily with tap water or freshly prepared GT (13.3 g/L). After 12 wk, the systolic blood pressure did not differ between treated and untreated nondiabetic or diabetic rats. However, body weight was less (P < 0.05) and glycemia was greater in diabetic SHR rats than in nondiabetic rats. Renal oxidative stress variables such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine expression, NADPH oxidase-dependent superoxide generation, and the expression of renal cortex Nox4 were greater (P < 0.05) in diabetic rats that received water (DW) than in nondiabetic rats that received water (CW). The 8-OHdG and NADPH oxidase-dependent superoxide generation were significantly less in rats treated with GT. Nitrotyrosine and Nox4 expression were significantly less in diabetic rats that received GT (DGT) than in DW. Likewise, the indices of renal injury, albuminuria, and renal expression of collagen IV were significantly greater in DW than in CW. These differences were significantly less in DGT than in DW. GT reestablished the redox state and reduced the indicators of nephropathy without altering glycemia and blood pressure levels in diabetic SHR. These findings suggest that the consumption of GT may ameliorate nephropathy in diabetic hypertensive patients.
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PMID:Green tea (Camellia sinensis) attenuates nephropathy by downregulating Nox4 NADPH oxidase in diabetic spontaneously hypertensive rats. 1905 45


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