Effects of allopurinol on endotoxin-induced increase in serum xanthine oxidase in the horse.
Using a modified bovine milk enzyme kinetic assay, xanthine oxidase activity of serum collected from 34 adult, healthy horses of both sexes was determined. Enzyme activity varied from 0 to 126 mU litre-1 with a mean of 44.95 +/- 21.05 mU litre-1. The optimal pH and temperature for maximal activity were 7.8 and 28 degrees C, respectively. Freezing the serum for four days at -70 degrees C did not destroy the enzyme activity. Various doses (25, 50 and 75 micrograms kg-1, intraperitoneally) of endotoxin (lipopolysaccharide D1 Escherichia coli O26:B6) previously known to have caused moderate to severe systemic clinical signs of endotoxaemia in horses produced a significant dose related increase in serum xanthine oxidase activity. Pretreatment (12 hours) with allopurinol (5 and 50 mg kg-1, intravenously [corrected]) significantly reduced the rise in xanthine oxidase activity in endotoxin (50 micrograms kg-1, intraperitoneally) treated horses. The results of this study suggest that xanthine oxidase catalysed production of superoxide radicals may play a role in the pathogenesis of endotoxaemia and that allopurinol, an alternate substrate, should be further evaluated for its therapeutic potential in endotoxin related systemic diseases in horses.
Lochner
F
F
Department of Medicine and Surgery, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
Sherban
D G
DG
Sangiah
S
S
Mauromoustakos
A
A
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D005615:Freezing; D006736:Horses / Q000097:blood*; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D013696:Temperature; D014969:Xanthine Oxidase / Q000097:blood*
D004731:Endotoxins; D008070:Lipopolysaccharides; D000493:Allopurinol; D014969:Xanthine Oxidase