Μetabοlοmic/Lipidοmic investigatiοns in equine atypical myοpathy and in vitrο screening οf nοn-pharmaceutical cοmpοunds

Atypical myopathy is a severe rhabdomyolysis caused by the ingestion of toxins found within the
horses’ environment. In the same toxic pasture, all horses are not prone to display clinical signs of atyp-
ical myopathy, despite the presence of toxins in their blood. The first objective aimed at improving the
physiopathology comprehension of the disease by investigating the horse blood metabolome. A study
comparing the metabolome of symptomatic and asymptomatic horses coming from the same pasture
had identified forty-six metabolites which belonged predominantly to fatty acid and amino acid chemical
classes. This study revealed characteristic metabolite changes in blood of affected horses and identified
several perturbed pathways (i.e. lipid, branched-chain amino acid and glycine metabolism). In addition,
five of these metabolites showed potential prognostic value. Then, a preliminary study focusing on blood
lipids revealed the potential of lipidomics in disease comprehension. Following metabolomic character-
ization, the subsequent objective aimed at preventing the occurrence of the disease by contributing to
the development of a feed complement. To do so, an in vitro intoxication model was developed enabling
the high-throughput screening of non-pharmaceutical compounds. In these experiments, an all-or-none
cytotoxicity’s response was observed with small concentration difference of toxic metabolite. The toxic
metabolite triggered the cell death by apoptosis. In addition, several non-pharmaceutical compounds had
shown potential in vitro protective effect. Altogether, these results provide new insights in the patho-
physiology which might ultimately help scientists and field veterinarians to detect, prognosticate and
manage atypical myopathy.