Original Research ArticleGlucose impairs aspirin inhibition in platelets through a NAD(P)H oxidase signaling pathway

- Glucose and lactate reduce the effect of aspirin on platelet aggregation.
- The effect of glucose/lactate is associated with the activation of NAD(P)H oxidase and the formation of reactive oxygen species in platelets.
- The effect of glucose/lactate is not caused by the activation of thromboxane A2 receptors.

Hyperglycemia has been suggested to play a role in the increased platelet resistance to antiplatelet therapy in patients with diabetes mellitus. Exposure to high glucose impairs platelet inhibition by aspirin. It has been found that antioxidant agents reduce the effect of glucose, confirming the involvement of reactive oxygen species (ROS) in the effect of glucose. The aim of the study was to examine the mechanism of ROS increase by high glucose in aspirin-treated platelets. Platelet aggregation was measured by the optical method, and the production of ROS was detected using luminol-dependent horseradish peroxidase-enhanced chemiluminescence. We found that glucose did not affect ADP-induced platelet aggregation. However, it reduced the effect of aspirin on platelet aggregation, which was accompanied by an increase in ROS generation. The inhibition of NAD(P)H oxidase (NOX) prevented the glucose effect and ROS generation. The same result was recorded after the inhibition of p38 mitogen-activated protein kinases (p38 MAPK), phospholipase A2 (PLA2) or 12-lipoxygenase (12-LOX). The inhibition of TxA2 receptor did not decrease the effect of glucose indicating that the effect was not caused by activation of TxA2 receptors.