PDF《elder tree》

Descriptive Clinical Reports Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree S.

J. VALBERG*? , B. T. SPONSELLER? , A. D. HEGEMAN§ , J. EARING# , J. B. BENDER? , K. L. MARTINSON# , S. E. PATTERSON? and L. SWEETMAN? ? Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA ? Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA § Department of Horticultural Sciences, College of Food, Agricultural and Natural Resource Sciences, University of Minnesota, St Paul, Minnesota, USA # Department of Animal Science, College of Food, Agricultural and Natural Resource Sciences, University of Minnesota, St Paul, Minnesota, USA ? Center for Drug Design, Academic Health Center, University of Minnesota, St Paul, Minnesota, USA ? Institute of Metabolic Disease, Baylor Research Institute, Dallas, Texas, USA. *Correspondence email: [email protected];

Received: 17.07.12;

Accepted: 21.09.12 Summary Reasons for performing study: We hypothesised that seasonal pasture myopathy (SPM), which closely resembles atypical myopathy (AM), was caused by ingestion of a seed-bearing plant abundant in autumn pastures. Objectives: To identify a common seed-bearing plant among autumn pastures of horses with SPM, and to determine whether the toxic amino acid hypoglycin A was present in the seeds and whether hypoglycin metabolites were present in SPM horse serum or urine. Methods: Twelve SPM cases,

11 SPM pastures and

23 control farms were visited to identify a plant common to all SPM farms in autumn. A common seed was analysed for amino acid composition (n = 7/7) by GC-MS and its toxic metabolite (n = 4/4) identi?ed in conjugated form in serum [tandem mass spectrometry (MS/MS)] and urine [gas chromatography (GC) MS]. Serum acylcarnitines and urine organic acid pro?les (n = 7) were determined for SPM horses. Results: Seeds from box elder trees (Acer negundo) were present on all SPM and 61% of control pastures. Hypoglycin A, known to cause acquired multiple acyl-CoA dehydrogenase de?ciency (MADD), was found in box elder seeds. Serum acylcarnitines and urine organic acid pro?les in SPM horses were typical for MADD. The hypoglycin A metabolite methylenecyclopropylacetic acid (MCPA), known to be toxic in other species, was found in conjugated form in SPM horse serum and urine. Horses with SPM had longer turn-out, more overgrazed pastures, and less supplemental feeding than control horses. Potential relevance: For the ?rst time, SPM has been linked to a toxin in seeds abundant on autumn pastures whose identi?ed metabolite, MCPA, is known to cause acquired MADD, the pathological mechanism behind SPM and AM. Further research is required to determine the lethal dose of hypoglycin A in horses, as well as factors that affect annual seed burden and hypoglycin A content in Acer species in North America and Europe. Keywords: horse;

muscle;

rhabdomyolysis;

beta oxidation;

multiple acyl-coA dehydrogenase Introduction A highly fatal muscle disease termed seasonal pasture myopathy (SPM) has been described for many decades in horses on pastures in the Midwestern USA and eastern Canada [1C3]. A similar disorder called atypical myopathy (AM),notedwithincreasingfrequency,existsintheUKandNorthernEurope [4C6]. Outbreaks of SPM and AM vary from year to year and are seasonal, with most cases occurring in the autumn and fewer cases occurring in the subsequentspring[5,7].InNorthAmerica,onlyafewhorsesareaffectedon agivenpasture,whereasinEuropelargeoutbreaksoccurwithmanyhorses on the same premises being affected [2,5,6]. Horses that develop SPM and AM are usually kept on sparse pastures with an accumulation of dead leaves, deadwood and trees in or around the pastures [5,6], often without being fed supplemental hay or grain [2]. Affected horses develop severe acute myonecrosis involving respiratory and postural muscles, and myoglobinuria, which in at least 75% of cases leads to death within