Oral treatment with an antioxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with type II diabetes.
OBJECTIVE
To determine whether raxofelast, a new water soluble antioxidant 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 II diabetes and as controls ten healthy men matched with them for age with raxofelast (600 mg twice daily) for 1 week. Plasma 8-epi-PGF(2a), a non-enzymic oxidation product of arachidonic acid was measured by gas chromatography/mass spectrometry as an index of oxidative stress. Forearm vasodilator responses to brachial artery infusion of acetylcholine (7.5, 15 and 30 microg min(-1)) and of the nitric oxide donor nitroprusside (1, 3 and 10 microg min(-1)) were measured by strain gauge plethysmography.


RESULTS
Plasma concentrations of 8-epi-PGF(2a), were greater in diabetic than in control men (0.99 +/- 0.20 vs 0.18 +/- 0.01 nmol 1(-1), means +/- SEM, p < 0.001) and fell after raxofelast (from 0.99 +/- 0.20 to 0.47 +/- 0.07 nmol 1(-1), p < 0.05) in diabetic men but not in control men. Blood flow responses to acetylcholine were lower (p < 0.05) in diabetic than in control men (7.4 +/- 1.0 vs 12.9 +/- 2.3 ml min(-1) x 100 ml(-1) for the highest dose). In diabetic men, but not in control men, raxofelast increased (p < 0.05) blood flow responses to acetylcholine (from 7.4 +/- 1.0 m x min(-1) x 100 ml(-1) to 11.3 +/- 2.3 ml x min(-1) x 100 ml(-1) at highest dose). Blood flow responses to nitroprusside were similar in control and diabetic men and in both groups were similar before and after raxofelast.


CONCLUSIONS
Oral treatment with raxofelast for 1 week reduces oxidative stress and improves endothelial function in men with Type II diabetes.
Chowienczyk
P J
PJ
Department of Clinical Pharmacology, Centre for Cardiovascular Biology and Medicine, King's College, London, UK.
Brett
S E
SE
Gopaul
N K
NK
Meeking
D
D
Marchetti
M
M
Russell-Jones
D L
DL
Anggård
E E
EE
Ritter
J M
JM
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001572:Benzofurans / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000975:Antioxidants; D001572:Benzofurans; D015415:Biomarkers; D020030:Nitric Oxide Donors; D014810:Vitamin E; D009599:Nitroprusside; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D000109:Acetylcholine; C071049:Raxofelast