Effect of allopurinol on the formation of reactive oxygen species during intense exercise in the horse.
Allopurinol was administered to six horses in a cross-over study to determine the relative contribution of xanthine oxidase (XO) activity to the formation of reactive oxygen species (ROS) in the horse during intense exercise. Exercise increased the mean (SEM) plasma lipid hydroperioxide concentration to a maximum of 492.7 (33.4) microM within one minute of exercise completion and maximum levels of both oxidised glutathione (GSSG) in haemolysates of red blood cells and the glutathione redox ratio (GRR) occurred 20 minutes after exercise (87.2 [12.2] microM and 8.9 [0.9] per cent, respectively). Allopurinol significantly reduced lipid hydroperoxides, GSSG and the GRR at the corresponding maximal times after exercise measured during control exercise (217.5 [32.1] microM. 63.8 [8.6] microM and 6.8 [0.7] per cent, respectively). Significantly higher levels of hypoxanthine and xanthine were measured after exercise in the plasma of horses that received allopurinol than in control horses, although uric acid levels remained constant. In control horses, plasma uric acid concentrations increased after exercise to a maximum 20 minutes after exercise of 28.1 (2.6) microM, significantly higher than in horses given allopurinol (9.6 [1.3] microM). The results show that the inhibition of XO by allopurinol leads to a decrease in the formation of ROS during exercise, and thus a reduction in oxidative stress.
Mills
P C
PC
Physiology Unit, Equine Centre, Animal Health Trust, Suffolk.
Smith
N C
NC
Harris
R C
RC
Harris
P
P
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005080:Exercise Test / Q000662:veterinary; D005260:Female; D005978:Glutathione / Q000097:blood; D006736:Horses / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D019271:Hypoxanthine / Q000097:blood; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D018384:Oxidative Stress; D010117:Oxypurinol / Q000097:blood; D010805:Physical Conditioning, Animal / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology*; D011685:Purine Nucleotides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D014527:Uric Acid / Q000097:blood; D019820:Xanthine; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000502:physiology; D014970:Xanthines / Q000097:blood
D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D011685:Purine Nucleotides; D017382:Reactive Oxygen Species; D014970:Xanthines; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D000493:Allopurinol; D014969:Xanthine Oxidase; D010117:Oxypurinol; D005978:Glutathione