Oral treatment with an antioxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with Type II diabetes

Aims/hypothesis. To determine whether raxofelast, a new water soluble antio xidant decreases oxidative stress and improves endothelial function in men with Type II (non-insulin dependent) diabetes mellitus. Methods. We treated ten normotensive, normocholesterolaemic men with Type I I diabetes and as controls ten healthy men matched with them for age with r axofelast (600 mg twice daily) for 1 week. Plasma 8-epi-PGF(2 alpha), a non -enzymic oxidation product of arachidonic acid was measured by gas chromato graphy/mass spectrometry as an index of oxidative stress. Forearm vasodilat or responses to brachial artery infusion of acetylcholine (7.5, 15 and 30 m u g min(-1)) and of the nitric oxide donor nitroprusside (1, 3 and 10 mu g min(-1)) were measured by strain gauge plethysmography. Results. Plasma concentrations of 8-epi-PGF(2 alpha) were greater in diabet ic than in control men (0.99 +/- 0.20 vs 0.18 +/- 0.01 nmol l(-1), means +/ - SEM, p < 0.001) and fell after raxofelast (from 0.99 +/- 0.20 to 0.47 +/- 0.07 nmol l(-1), p < 0.05) in diabetic men but not in control men. Blood f low responses to acetylcholine were lower (p < 0.05) in diabetic than in co ntrol men (7.4 +/- 1.0 vs 12.9 +/- 2.3 ml.min(-1).100 ml(-1) for the highes t dose). In diabetic men, but not in control men, raxofelast increased (p < 0.05) blood now responses to acetylcholine (from 7.4 +/- 1.0 ml. min(-1).1 00 ml(-1) to 11.3 +/- 2.3 ml min(-1) 100 ml(-1) at highest dose). Blood flo w responses to nitroprusside were similar in control and diabetic men and i n both groups were similar before and after raxofelast, Conclusion/interpretation. Oral treatment with raxofelast for 1 week reduce s oxidative stress and improves endothelial function in men with Type II di abetes.