ABSTRACT
Equine atypical myopathy (AM) is a severe environmental intoxication linked to the ingestion of protoxins contained in seeds and seedlings of the sycamore maple (Acer pseudoplatanus) in Europe. The toxic metabolites cause a frequently fatal rhabdomyolysis syndrome in grazing horses. Since these toxic metabolites can also be present in cograzing horses, it is still unclear as to why, in a similar environmental context, some horses show signs of AM, whereas others remain clinically healthy. Label-free proteomic analyses on the serum of 26 diseased AM, 23 cograzers, and 11 control horses were performed to provide insights into biological processes and pathways. A total of 43 and 44 differentially abundant proteins between "AM vs cograzing horses" and "AM vs control horses" were found. Disease-linked changes in the proteome of different groups were found to correlate with detected amounts of toxins, and principal component analyses were performed to identify the 29 proteins representing a robust AM signature. Among the pathway-specific changes, the glycolysis/gluconeogenesis pathway, the coagulation/complement cascade, and the biosynthesis of amino acids were affected. Sycamore maple poisoning results in a combination of inflammation, oxidative stress, and impaired lipid metabolism, which is trying to be counteracted by enhanced glycolysis.
ABSTRACT
Thoroughbred (TB) racehorses undergo rigorous conditioning programs to optimize their physical and mental capabilities through varied exercise sessions. While conventional investigations focus on limited hematological and biochemical parameters, this field study employed untargeted metabolomics to comprehensively assess metabolic responses triggered by exercise sessions routinely used in TB conditioning. Blood samples were collected pre- and post-exercise from ten racehorses, divided into two groups based on exercise intensity: high intensity (n = 6, gallop at ± 13.38 m/s, 1400 m) and moderate intensity (n = 4, soft canter at ± 7.63 m/s, 2500 m). Intensity was evaluated through monitoring of the speed, heart rate, and lactatemia. Resting and 30 min post-exercise plasma samples were analyzed using ultraperformance liquid chromatography coupled with high-resolution mass spectrometry. Unsupervised principal component analysis revealed exercise-induced metabolome changes, with high-intensity exercise inducing greater alterations. Following high-intensity exercise, 54 metabolites related to amino acid, fatty acid, nucleic acid, and vitamin metabolism were altered versus 23 metabolites, primarily linked to fatty acid and amino acid metabolism, following moderate-intensity exercise. Metabolomics confirmed energy metabolism changes reported by traditional biochemistry studies and highlighted the involvement of lipid and amino acid metabolism during routine exercise and recovery, aspects that had previously been overlooked in TB racehorses.
ABSTRACT
Equine atypical myopathy is a seasonal intoxication of grazing equids. In Europe, this poisoning is associated with the ingestion of toxins contained in the seeds and seedlings of the sycamore maple (Acer pseudoplatanus). The toxins involved in atypical myopathy are known to inhibit ß-oxidation of fatty acids and induce a general decrease in mitochondrial respiration, as determined by high-resolution respirometry applied to muscle samples taken from cases of atypical myopathy. The severe impairment of mitochondrial bioenergetics induced by the toxins may explain the high rate of mortality observed: about 74% of horses with atypical myopathy die, most within the first two days of signs of poisoning. The mechanism of toxicity is not completely elucidated yet. To improve our understanding of the pathological process and to assess therapeutic candidates, we designed in vitro assays using equine skeletal myoblasts cultured from muscle biopsies and subjected to toxins involved in atypical myopathy. We established that equine primary myoblasts do respond to one of the toxins incriminated in the disease.
