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Case-control exercise challenge study on the pathogenesis of high serum gamma-glutamyl transferase activity in racehorses.
Abstract: High serum γ-glutamyl-transferase (GGT) activity syndrome in racehorses has been associated with maladaption to exercise. Investigation of affected horses before and immediately after standard exercise may provide critical insight into the syndrome's pathophysiology. Objective: To investigate blood biomarker changes in actively competing racehorses with high GGT activity associated with an exercise challenge. Methods: Case-control study. Methods: High GGT case (age: 2-3 years) and normal GGT control (age: 2-7 years) pairs (3 Thoroughbred, 4 Standardbred pairs) at least 3 months into their training/racing season were included. Horses with a recent history of high GGT activity (≥50 IU/L) without additional biochemical evidence of liver disease were identified by veterinarians. Horses were tested again in the week prior to a planned exercise challenge to confirm persistent increases in GGT activity. Controls from the same stable with similar training/racing intensity and serum GGT activity ≤36 IU/L were matched with each case. Blood samples were obtained immediately before, 15 and 120 min after exercise. Pre-exercise serum samples were analysed for baseline select serum chemistries, selenium and vitamin E concentrations. Cortisol concentration and markers of oxidative status were measured in serum or plasma for all time points. Individual serum bile acid and coenzyme Q10 concentrations, plasma lipid mediator (fatty acids, oxylipids, isoprostanes) concentrations and targeted metabolomics analyses were performed using liquid chromatography-mass spectrometry. Serum viral PCR for equine hepaci- and parvovirus was performed in each animal. Results: Cases had higher baseline concentrations of total glutathione, taurocholic acid, cortisol and cholesterol concentrations and higher or lower concentrations of specific oxylipid and isoprostane mediators, but there were no case-dependent changes after exercise. Conclusions: Small sample size. Conclusions: Results indicated that glutathione metabolism was altered in high GGT horses. Enhanced glutathione recycling and mild cholestasis are possible explanations for the observed differences.
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Publication Date: 2022-05-25 PubMed ID: 35491961DOI: 10.1111/evj.13584Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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This research investigated the changes in blood biomarkers in racehorses with high gamma-glutamyl transferase (GGT) activity in relation to an exercise challenge. It identified unusual glutathione metabolism in affected horses, suggesting enhanced glutathione recycling and mild cholestasis as possible explanations for observed differences.
Research Objective and Methodology
- The research aimed to explore the blood biomarker changes in racehorses affected by high GGT activity syndrome after regular exercise. GGT activity syndrome has previously been linked with a horse’s poor adaptation to exercise.
- A case-control study was conducted involving horses with high GGT activity and those with normal GGT activity. The former were between two and three years old while the latter ranged from two to seven years old. This selection aids in providing a reasonably comparative study perspective, given the horses are of similar ages and life stage.
- Horses with a recorded history of high GGT activity, but without additional biochemical indications of liver disease, were identified and selected by veterinarians. These horses were tested again just before an exercise challenge to confirm continual high GGT activity.
- Control horses, which had normal GGT activity, were selected from the same stables. The selection helped ensure that other environmental factors outside the intended variables—like feeding, weather conditions, and exercise routine—remained constant across cases and controls.
Procedure and Measurements
- Blood samples were extracted immediately before, and then 15 and 120 minutes after exercise. The blood samples were taken at various intervals to note any changes in the biomarkers due to exercise.
- Baseline serum samples were analyzed for various chemistries, selenium and vitamin E concentrations, which serve as crucial data for interpreting the health status of the horses.
- The research also explored cortisol concentration and signs of oxidative status in all serum or plasma samples.
- Liquid chromatography-mass spectrometry was used to measure individual serum bile acid and coenzyme Q10 concentrations, and plasma lipid mediator concentrations. This technique provided a comprehensive understanding of the metabolic status of the horses.
Results and Conclusions
- Findings revealed that horses with high GGT displayed higher baseline concentrations of total glutathione, taurocholic acid, cortisol, and cholesterol. Interestingly, there were no evident changes in these biomarkers post-exercise.
- Some specific oxylipid and isoprostane mediators were found in higher or lower concentrations in the cases, but the difference was not significant after exercise.
- One primary conclusion is that the metabolism of glutathione—a primary antioxidant in the body—is changed in horses with high GGT.
- The results point towards enhanced glutathione recycling or mild cholestasis as possible explanations for the differences observed between the normal and high GGT cohorts.
Cite This Article
APA
Mann S, Abuelo A, Stokol T, Wakshlag JJ, Bayly W, Reed S, Gandy J, Ramsay JD, Divers TJ.
(2022).
Case-control exercise challenge study on the pathogenesis of high serum gamma-glutamyl transferase activity in racehorses.
Equine Vet J, 55(2), 182-193.
https://doi.org/10.1111/evj.13584 Publication
Researcher Affiliations
- Cornell University Department of Population Medicine and Diagnostic Sciences, Cornell College of Veterinary Medicine, Ithaca, New York, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
- Cornell University Department of Population Medicine and Diagnostic Sciences, Cornell College of Veterinary Medicine, Ithaca, New York, USA.
- Cornell University Department of Clinical Sciences, Cornell College of Veterinary Medicine, Ithaca, New York, USA.
- Department of Veterinary Clinical Science, Washington State University, Pullman, Washington, USA.
- Rood & Riddle Equine Hospital, Lexington, Kentucky, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
- Cornell University Department of Clinical Sciences, Cornell College of Veterinary Medicine, Ithaca, New York, USA.
MeSH Terms
- Horses
- Animals
- Case-Control Studies
- Hydrocortisone
- gamma-Glutamyltransferase
- Physical Conditioning, Animal / physiology
Grant Funding
- 84870-2017 / Grayson-Jockey Club Research Foundation
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