Total Radical-Trapping Antioxidant Parameter in NIDDM Patients

Ceriello, Antonio; Bortolotti, Nadia; Falleti, Edmondo; Taboga, C.; Tonutti, Laura; Crescentini, Adriana; Motz, Enrico; Lizzio, Sebastiano; Russo, Assunta; Bartoli, Ettore

doi:10.2337/diacare.20.2.194

Cited by 148 publications

(85 citation statements)

References 20 publications

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“…There is ample clinical and experimental evidence showing diabetes per se as a state of oxidative stress (14,(37)(38)(39)(40). Likewise, diabetic pregnancy is associated with oxidative stress (41)(42)(43), and the assumption that diabetic embryopathy may be induced by enhanced ROS metabolism is supported by several studies.…”

Section: Discussionmentioning

confidence: 99%

Maternal Diabetes In Vivo and High Glucose In Vitro Diminish GAPDH Activity in Rat Embryos

2003

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The aim of the present study was to investigate whether diabetic embryopathy may be associated with the inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) resulting from an excess of reactive oxygen species (ROS) in the embryo. Recent demonstrations of enhanced ROS production in mitochondria of bovine aortic endothelial cells exposed to high glucose have supported the idea that the pathogenesis of diabetic complications may involve ROS-induced GAPDH inhibition. We investigated whether a teratogenic diabetic environment also inhibits embryonic GAPDH activity and alters GAPDH gene expression and whether antioxidants diminish such GAPDH inhibition. In addition, we determined whether the inhibition of GAPDH with iodoacetate induces dysmorphogenesis, analogous to that caused by high glucose concentration, and whether antioxidants modulated the putative teratogenic effect of such direct GAPDH inhibition. We found that embryos from diabetic rats and embryos cultured in high glucose concentrations showed decreased activity of GAPDH (by 40 -60%) and severe dysmorphogenesis on gestational days 10.5 and 11.5. GAPDH mRNA was decreased in embryos of diabetic rats compared to control embryos. Supplementing the high-glucose culture with the antioxidant N-acetylcysteine (NAC) increased GAPDH activity and diminished embryonic dysmorphogenesis. Embryos cultured with iodoacetate showed both decreased GAPDH activity and dysmorphogenesis; supplementing the culture with NAC increased both parameters toward normal values. In conclusion, dysmorphogenesis caused by maternal diabetes is correlated with ROS-induced inhibition of GAPDH in embryos, which could indicate that inhibition of GAPDH plays a causal role in diabetic embryopathy. Diabetes

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Section: Discussionmentioning

confidence: 99%

Maternal Diabetes In Vivo and High Glucose In Vitro Diminish GAPDH Activity in Rat Embryos

2003

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“…The thiol group of cysteinyl side chains in proteins is particularly susceptible to oxidative modification (13). In fact, the concentration of plasma protein-bound thiols was found to be lower in type 2 diabetic patients than in control individuals (14). Alternatively, cellular protection against oxidative damage of proteins involves two thiol-disulfide oxidoreductase systems, i.e., the thioredoxin (Trx) and glutaredoxin (Grx) systems (13,15).…”

Section: Introductionmentioning

confidence: 99%

Methylglyoxal Causes Dysfunction of Thioredoxin and Thioredoxin Reductase in Endothelial Cells

et al. 2009

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Abstract. Methylglyoxal (MG), a reactive dicarbonyl produced during glucose metabolism, induces oxidative stress and apoptosis. Under hyperglycemic conditions, the abnormal accumulation of MG is related to the development of diabetic complications. We examined the effects of MG on thioredoxin (Trx) and glutaredoxin (Grx) systems, two thiol-disulfide oxidoreductase systems that protect against oxidative damage of proteins, in bovine aortic endothelial cells (BAECs). The levels of protein carbonyls as markers of protein oxidation increased in BAECs exposed to MG at 5 mM, resulting in the loss of cell viability. Western blot analysis demonstrated that Trx protein level decreased when BAECs were exposed to 5 mM MG. MG also inactivated Trx reductase, which maintains Trx in the reduced/active state. Moreover, peroxiredoxin, which is dependent on Trx and Trx reductase to maintain its reduced state, was oxidized by 5 mM MG. No significant difference in the levels of Trx, Trx reductase, or peroxiredoxin was observed in BAECs exposed to MG at 1 mM; this concentration had little effect on protein carbonyl formation and cell viability. MG failed to decrease Grx activity, indicating that Trx is more susceptible to MG than Grx. Taken together, these findings suggest that MG causes dysfunction of the Trx system, including Trx and Trx reductase, in BAECs.

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“…The alterations of hemostatic and thrombotic parameters are among the principal causes for the cardiovascular risk increase in diabetic patients (3). It has also been suggested that oxidative stress can contribute to diabetic vascular complications (4), and lower antioxidant defenses in diabetes have been described (5).…”

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confidence: 99%

Primary Prevention of Cardiovascular Events With Low-Dose Aspirin and Vitamin E in Type 2 Diabetic Patients

et al. 2003

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OBJECTIVE -We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes. RESEARCH DESIGN AND METHODS -The Primary Prevention Project (PPP) is arandomized, open trial with a two-by-two factorial design aimed to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors. The primary end point was a composite end point of cardiovascular death, stroke, or myocardial infarction. A total of 1,031 people with diabetes in the PPP, aged Ն50 years, without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics.RESULTS -The PPP trial was prematurely stopped (after a median of 3.7 years) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors. In diabetic patients, aspirin treatment was associated with a nonsignificant reduction in the main end point (relative risk [RR] ϭ 0.90, 95% CI 0.50 -1.62) and in total cardiovascular events (0.89, 0.62-1.26) and with a nonsignificant increase in cardiovascular deaths (1.23, 0.69 -2.19). In nondiabetic subjects, RRs for the main end point, total cardiovascular events, and cardiovascular deaths were 0.59 (0.37-0.94), 0.69 (0.53-0.90), and 0.32 (0.14 -0.72), respectively. No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects. CONCLUSIONS -Our data suggest a lower effect of primary prevention of cardiovascular disease (CVD) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors. If confirmed, these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation, thus making the balance between benefits and harms of aspirin treatment unfavorable. Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed.

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Total Radical-Trapping Antioxidant Parameter in NIDDM Patients

Cited by 148 publications

References 20 publications

Maternal Diabetes In Vivo and High Glucose In Vitro Diminish GAPDH Activity in Rat Embryos

Maternal Diabetes In Vivo and High Glucose In Vitro Diminish GAPDH Activity in Rat Embryos

Methylglyoxal Causes Dysfunction of Thioredoxin and Thioredoxin Reductase in Endothelial Cells

Primary Prevention of Cardiovascular Events With Low-Dose Aspirin and Vitamin E in Type 2 Diabetic Patients

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