Effects of allopurinol on endotoxin-induced increase in serum xanthine oxidase in the horse.
Abstract: 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.
Publication Date: 1990-07-01 PubMed ID: 2200092
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates the effects of allopurinol, a medication typically used for gout, on endotoxin-induced serum xanthine oxidase activity in horses. It indicates that allopurinol may potentially help in reducing the increase in xanthine oxidase activity due to endotoxin exposure in horses.
About the Research
- The research was conducted on 34 adult, healthy horses of both sexes. The enzyme activity in the serum of these horses was determined using a modified bovine milk enzyme kinetic assay.
- Xanthine oxidase is an enzyme that plays a key role in the purine catabolism pathway, a metabolic pathway that leads to the formation of uric acid. This enzyme has been implicated in the pathogenesis of certain diseases due to its ability to form reactive oxygen species, such as superoxide radicals.
Main Findings and Experiment Design
- The optimal conditions for the maximal activity of the enzyme were a pH of 7.8 and a temperature of 28 degrees Celsius.
- The serum was frozen for four days at -70 degrees Celsius without any loss in enzyme activity.
- The horses were also given various doses (25, 50, and 75 micrograms per kg body weight, intraperitoneally) of endotoxin (lipopolysaccharide D1 Escherichia coli O26:B6), which had been previously shown to cause moderate to severe systemic clinical signs of endotoxemia in horses. This endotoxin significantly increased the serum xanthine oxidase activity in a dose-related manner.
- When horses were pre-treated with allopurinol (5 and 50 mg/kg, intravenously), it significantly reduced this endotoxin-induced increase in xanthine oxidase activity.
Implications and Significance
- The results of this study suggest that xanthine oxidase may be involved in the development of endotoxemia, a condition characterized by the presence of endotoxins in the blood, which can potentially lead to sepsis.
- The researchers also propose that allopurinol may have potential therapeutic value in managing endotoxin related systemic diseases in horses, as it has been shown to reduce the increase in serum xanthine oxidase activity resulting from endotoxin administration.
- The researchers recommend further evaluation of allopurinol for its potential therapeutic application in managing systemic diseases related to endotoxins in horses.
Cite This Article
APA
Lochner F, Sherban DG, Sangiah S, Mauromoustakos A.
(1990).
Effects of allopurinol on endotoxin-induced increase in serum xanthine oxidase in the horse.
Res Vet Sci, 49(1), 104-109.
Publication
Researcher Affiliations
- Department of Medicine and Surgery, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
MeSH Terms
- Allopurinol / pharmacology
- Animals
- Drug Interactions
- Endotoxins / pharmacology
- Escherichia coli
- Female
- Freezing
- Horses / blood
- Hydrogen-Ion Concentration
- Lipopolysaccharides / pharmacology
- Male
- Temperature
- Xanthine Oxidase / blood
Citations
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