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.
Department of Medicine and Surgery, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
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F
Lochner
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Sherban
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Sangiah
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Mauromoustakos
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