In Vitro Assays for the Assessment of Impaired Mitochondrial Bioenergetics in Equine Atypical Myopathy

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.

Impaired Mitochondrial Bioenergetics under Pathological Conditions

“…Therefore, measurement of mitochondrial bioenergetics by a new frozen respirometry protocol utilizing non-invasive analysis might facilitate the clinical monitoring of mitochondrial function in samples collected at remote sites [20]. In addition, mitochondrial oxidation and substrate oxidation measurement by in vitro myopathy assays was also considered a prognostic method for use on equine muscle biopsies [21].…”