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Low dose of acetylsalicylic acid and oxidative stress-mediated endothelial dysfunction in diabetes: a short-term evaluation.

Tassone EJ, Perticone M, Sciacqua A, Mafrici SF, Settino C, Malara N, Mollace V, Sesti G, Perticone F - Acta Diabetol (2014)

Bottom Line: As expected, after 4 weeks of treatment, ASA induced a significant reduction of plasma thromboxane-A2, as a consequence of cyclooxygenase-1 inhibition.By contrast, ASA significantly increased the plasma and urine 8-iso-PGF2α, a well-known prothrombotic molecule, parallel to an increase of plasma NOX2 levels.The enhancement of this oxidative pathway is associated with a significant impairment of endothelial vasodilation, assessed by reactive hyperemia index (RHI).

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100, Catanzaro, Italy, eli.jo@alice.it.

ABSTRACT
Current guidelines suggest the use of low doses of acetylsalicylic acid (ASA) for patients with diabetes mellitus (DM) in primary prevention. However, the evidences demonstrating the beneficial effect of ASA in primary prevention are conflicting. In this pilot study, we evaluated in a group of diabetic patients, in primary prevention, the impact of ASA treatment on oxidative stress and vascular function. We enrolled 22 newly diagnosed diabetic patients, without any previous clinical evidence of cardiovascular disease, to receive, in primary prevention, ASA (100 mg/daily). We tested, in basal condition, after 4 weeks of ASA administration and after 4 weeks of pharmacological washout, the impact of ASA treatment on endothelial function, assessed by a semipletysmographic method, measuring the main oxidative stress parameters related to it. As expected, after 4 weeks of treatment, ASA induced a significant reduction of plasma thromboxane-A2, as a consequence of cyclooxygenase-1 inhibition. By contrast, ASA significantly increased the plasma and urine 8-iso-PGF2α, a well-known prothrombotic molecule, parallel to an increase of plasma NOX2 levels. The enhancement of this oxidative pathway is associated with a significant impairment of endothelial vasodilation, assessed by reactive hyperemia index (RHI). The pharmacological washout reverted all parameters to basal condition. Our findings suggest that ASA utilization for primary prevention in diabetic patients causes a significant increase of oxidative stress burden impairing the vascular function. Present data, if confirmed on a larger population, could permanently discourage the use of the ASA for the primary prevention in patients with DM.

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Related in: MedlinePlus

Diagram graphically reports the effects of ASA on vascular oxidative stress leading to endothelial dysfunction. COX1 inhibition triggers an escape pathway that is able to promote the production of isoprostanes that, in turn, contribute to impair the endothelium-dependent vasodilation
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Fig5: Diagram graphically reports the effects of ASA on vascular oxidative stress leading to endothelial dysfunction. COX1 inhibition triggers an escape pathway that is able to promote the production of isoprostanes that, in turn, contribute to impair the endothelium-dependent vasodilation

Mentions: In this study, we evaluated, in a group of newly diagnosed type 2 diabetic patients, the impact of ASA treatment in primary prevention on oxidative stress and vascular function. We demonstrated that ASA administration induces a significant increase in global oxidative burden, as shown by the increase of plasma and urine 8-iso-PGF2α, a well-known proaggregating and prothrombotic molecule [18]. As already speculated, the increase of 8-iso-PGF2α could be promoted, indirectly, by the ASA-induced inhibition of the COX1 enzyme that, in turn, leads to the triggering of an escape pathway of isoprostanes formation [16, 19]. Moreover, in diabetic patients, there is per se an increased activity of the NADPH oxidase that is responsible for the increased production of ROS [8], which are able to interact with arachidonic acid to form isoprostanes [20]. ASA treatment is also able to increase NOX2 levels, contributing to cellular oxidative burden in ROS production. In this way, the treatment with ASA, by selectively inhibiting COX1, prevents the arachidonic acid contribution to generate Tx-A2, favoring the switch of the substrate for the isoprostanes production [21]. According to this, our data show that ASA induces a significant reduction in plasma Tx-A2 and increases the plasma and urinary levels of 8-iso-PGF2α (Fig. 5). Of interest, Gonçalves and corkers recently reported that concomitant use of metformin and ASA in diabetic patients can reduce levels of urinary biomarkers of oxidative stress [22], offering new important therapeutic implications for antidiabetic drugs.Fig. 5


Low dose of acetylsalicylic acid and oxidative stress-mediated endothelial dysfunction in diabetes: a short-term evaluation.

Tassone EJ, Perticone M, Sciacqua A, Mafrici SF, Settino C, Malara N, Mollace V, Sesti G, Perticone F - Acta Diabetol (2014)

Diagram graphically reports the effects of ASA on vascular oxidative stress leading to endothelial dysfunction. COX1 inhibition triggers an escape pathway that is able to promote the production of isoprostanes that, in turn, contribute to impair the endothelium-dependent vasodilation
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4374120&req=5

Fig5: Diagram graphically reports the effects of ASA on vascular oxidative stress leading to endothelial dysfunction. COX1 inhibition triggers an escape pathway that is able to promote the production of isoprostanes that, in turn, contribute to impair the endothelium-dependent vasodilation
Mentions: In this study, we evaluated, in a group of newly diagnosed type 2 diabetic patients, the impact of ASA treatment in primary prevention on oxidative stress and vascular function. We demonstrated that ASA administration induces a significant increase in global oxidative burden, as shown by the increase of plasma and urine 8-iso-PGF2α, a well-known proaggregating and prothrombotic molecule [18]. As already speculated, the increase of 8-iso-PGF2α could be promoted, indirectly, by the ASA-induced inhibition of the COX1 enzyme that, in turn, leads to the triggering of an escape pathway of isoprostanes formation [16, 19]. Moreover, in diabetic patients, there is per se an increased activity of the NADPH oxidase that is responsible for the increased production of ROS [8], which are able to interact with arachidonic acid to form isoprostanes [20]. ASA treatment is also able to increase NOX2 levels, contributing to cellular oxidative burden in ROS production. In this way, the treatment with ASA, by selectively inhibiting COX1, prevents the arachidonic acid contribution to generate Tx-A2, favoring the switch of the substrate for the isoprostanes production [21]. According to this, our data show that ASA induces a significant reduction in plasma Tx-A2 and increases the plasma and urinary levels of 8-iso-PGF2α (Fig. 5). Of interest, Gonçalves and corkers recently reported that concomitant use of metformin and ASA in diabetic patients can reduce levels of urinary biomarkers of oxidative stress [22], offering new important therapeutic implications for antidiabetic drugs.Fig. 5

Bottom Line: As expected, after 4 weeks of treatment, ASA induced a significant reduction of plasma thromboxane-A2, as a consequence of cyclooxygenase-1 inhibition.By contrast, ASA significantly increased the plasma and urine 8-iso-PGF2α, a well-known prothrombotic molecule, parallel to an increase of plasma NOX2 levels.The enhancement of this oxidative pathway is associated with a significant impairment of endothelial vasodilation, assessed by reactive hyperemia index (RHI).

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100, Catanzaro, Italy, eli.jo@alice.it.

ABSTRACT
Current guidelines suggest the use of low doses of acetylsalicylic acid (ASA) for patients with diabetes mellitus (DM) in primary prevention. However, the evidences demonstrating the beneficial effect of ASA in primary prevention are conflicting. In this pilot study, we evaluated in a group of diabetic patients, in primary prevention, the impact of ASA treatment on oxidative stress and vascular function. We enrolled 22 newly diagnosed diabetic patients, without any previous clinical evidence of cardiovascular disease, to receive, in primary prevention, ASA (100 mg/daily). We tested, in basal condition, after 4 weeks of ASA administration and after 4 weeks of pharmacological washout, the impact of ASA treatment on endothelial function, assessed by a semipletysmographic method, measuring the main oxidative stress parameters related to it. As expected, after 4 weeks of treatment, ASA induced a significant reduction of plasma thromboxane-A2, as a consequence of cyclooxygenase-1 inhibition. By contrast, ASA significantly increased the plasma and urine 8-iso-PGF2α, a well-known prothrombotic molecule, parallel to an increase of plasma NOX2 levels. The enhancement of this oxidative pathway is associated with a significant impairment of endothelial vasodilation, assessed by reactive hyperemia index (RHI). The pharmacological washout reverted all parameters to basal condition. Our findings suggest that ASA utilization for primary prevention in diabetic patients causes a significant increase of oxidative stress burden impairing the vascular function. Present data, if confirmed on a larger population, could permanently discourage the use of the ASA for the primary prevention in patients with DM.

Show MeSH
Related in: MedlinePlus