Effects of allopurinol in experimental endotoxin shock in horses.
Abstract: The effect of allopurinol pretreatment 12 hours before an intraperitoneal challenge with a sublethal dose of Escherichia coli endotoxin (50 micrograms kg-1) was evaluated in 18 horses. The horses were divided among three equal groups: 1-endotoxin alone; 2-5 mg allopurinol kg-1 bodyweight plus endotoxin; and 3-50 mg allopurinol kg-1 bodyweight plus endotoxin. A variety of evaluation parameters were used. No differences among the groups were noted in rectal temperature, heart rate, respiration rate, haematological values, blood PaO2, blood PaCO2, blood pH or blood bicarbonate. Significant (P less than 0.05) differences between the groups were noted as regards the changes in capillary refill time, base excess, blood glucose, blood lactate, blood beta-glucuronidase and recumbency time. The protection afforded by 5 mg allopurinol kg-1 appeared to be superior to that with 50 mg allopurinol kg-1.
Publication Date: 1989-09-01 PubMed ID: 2678330
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research studied the impact of administering allopurinol, a medication usually used to treat gout, on horses that were induced with non-lethal E. coli endotoxin. The researchers found that after applying a variety of evaluation tools, administering allopurinol before inducing endotoxin shock resulted in significant changes in some parameters, including capillary refill time, base excess, blood glucose, blood lactate, and more. Interestingly, a dose of 5mg per kg bodyweight of allopurinol provided better protection than a larger 50mg per kg bodyweight dose.
Methods of the Study
- The study was performed on 18 horses. These horses were evenly divided into three groups.
- The first group was given endotoxin alone to indicate an untreated control group.
- The second and third groups were pre-treated with allopurinol at doses of 5 mg and 50 mg per kg body weight respectively, 12 hours before being challenged with the endotoxin, to examine the impact of allopurinol pretreatment.
- In order to compare the results across these different groups, various parameters were evaluated. These included rectal temperature, heart rate, respiration rate, haematological values, blood oxygen concentration (PaO2), blood carbon dioxide levels (PaCO2), blood pH level, and blood bicarbonate.
Results of the Study
- In the parameters mentioned above, no significant differences were found among the three groups of horses. Thus, allopurinol treatment did not seem to have an effect on these physiological and blood-based parameters.
- However, significant differences were found as regards capillary refill time, base excess, blood glucose levels, blood lactate levels, blood beta-glucuronidase levels, and recumbency time (recumbency time refers to the period a horse spends lying down and being non-responsive due to a severe illness).
- Interestingly, the group of horses that received the lower dose of allopurinol (5 mg per kg bodyweight) appeared to fare better than the one receiving the higher dose (50 mg per kg bodyweight). This indicates that a higher dose of the drug doesn’t necessarily lead to better outcomes, and in fact, the opposite may be true.
Significance of the Research
- This study provides valuable insights into the potential use of allopurinol in preventing or mitigating endotoxin-induced shock in horses. More generally, this model could be further used to study interventions in endotoxin shock for a variety of animal species, including humans.
- The finding that a lower dose of allopurinol might be more effective than a higher dose is intriguing and worth further investigation.
Cite This Article
APA
Lochner F, Sangiah S, Burrows G, Shawley R, McNew R, Walker J.
(1989).
Effects of allopurinol in experimental endotoxin shock in horses.
Res Vet Sci, 47(2), 178-184.
Publication
Researcher Affiliations
- Department of Medicine and Surgery, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
MeSH Terms
- Allopurinol / pharmacology
- Allopurinol / therapeutic use
- Animals
- Blood Gas Analysis / veterinary
- Blood Glucose / analysis
- Body Temperature / drug effects
- Disease Models, Animal
- Endotoxins
- Escherichia coli
- Female
- Glucuronidase / blood
- Heart Rate / drug effects
- Hematocrit / veterinary
- Horse Diseases / blood
- Horse Diseases / physiopathology
- Horse Diseases / prevention & control
- Horses
- Hydrogen-Ion Concentration
- Lactates / blood
- Leukocyte Count / drug effects
- Leukocyte Count / veterinary
- Lipopolysaccharides
- Male
- Respiration / drug effects
- Shock, Septic / blood
- Shock, Septic / physiopathology
- Shock, Septic / prevention & control
- Shock, Septic / veterinary
Citations
This article has been cited 1 times.- Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol.. Pharmacol Rev 2006 Mar;58(1):87-114.
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