hypoglycin-a and Rhabdomyolysis

Intestinal absorption of hypoglycin A (HGA) and its metabolism are considered major prerequisites for atypical myopathy (AM). The increasing incidence and the high mortality rate of AM urgently necessitate new therapeutic and/or preventative approaches.. To identify a substance for oral administration capable of binding HGA in the intestinal lumen and effectively reducing the intestinal absorption of the toxin.. Experimental in vitro study.. Substances commonly used in equine practice (activated charcoal composition, di-tri-octahedral smectite, mineral oil and activated charcoal) were tested for their binding capacity for HGA using an in vitro incubation method. The substance most effective in binding HGA was subsequently tested for its potential to reduce intestinal HGA absorption. Jejunal tissues of 6 horses were incubated in Ussing chambers to determine mucosal uptake, tissue accumulation, and serosal release of HGA in the presence and absence of the target substance. Potential intestinal metabolism in methylenecyclopropyl acetic acid (MCPA)-conjugates was investigated by analysing their concentrations in samples from the Ussing chambers.. Activated charcoal composition and activated charcoal were identified as potent HGA binding substances with dose and pH dependent binding capacity. There was no evidence of intestinal HGA metabolism.. Binding capacity of adsorbents was tested in vitro using aqueous solutions, and in vivo factors such as transit time and composition of intestinal content, may affect adsorption capacity after oral administration.. For the first time, this study identifies substances capable of reducing HGA intestinal absorption. This might have major implications as a preventive measure in cograzers of AM affected horses but also in horses at an early stage of intoxication.

Topics: Acer; Adsorption; Animals; Antidotes; Charcoal; Drug Combinations; Horse Diseases; Horses; Hypoglycins; Kaolin; Plant Bark; Plant Poisoning; Quercus; Rhabdomyolysis; Seeds; Silicates; Silicon Dioxide

Equine atypical myopathy (AM) is a toxic rhabdomyolysis associated with ingestion of hypoglycin A, derived typically in Europe, from Acer pseudoplatanus tree. Despite the wide distribution of this tree species in the UK, the number of cases reported annually varies, and there has been an apparent increase in prevalence in recent years. Although AM was first recognised in the UK, epidemiological studies have never been conducted focused solely on this country.. To describe the spatiotemporal distribution, presentation, treatment and outcome of AM cases reported in the UK.. Retrospective case series.. British AM cases reported to the atypical myopathy alert website, between 2011 and 2015 were included (n = 224). Data were obtained via standardised epidemiological questionnaires from owners and veterinarians. Factors associated with survival were assessed using logistic regression.. Most cases reported were from England (87.9%). Survival was 38.6% (n = 73/189). Clinical factors associated with reduced odds of survival included, hypothermia (odds ratio [OR] 0.18; 95% confidence interval [CI] 0.06-0.57; P = 0.01), bladder distension (OR 0.11; CI 0.02-0.59; P = 0.01), tachycardia (OR 0.97; CI 0.94-0.99; P = 0.04) and serum creatine kinase activity >100,000 IU/L (OR 0.17; CI 0.04-0.68; P = 0.01) in the univariable analysis as well as recumbency. The latter was the only sign retained in multivariable analysis (OR = 0.19; CI 0.06-0.62; P = 0.006). Administration of vitamins during the disease was associated with survival (OR 3.75; CI 1.21-11.57; P = 0.02).. Reporting cases to the Atypical Myopathy Alert Group is voluntary; therefore, under-reporting will result in underestimation of AM cases; furthermore, direct owner-reporting could have introduced misdiagnosis bias.. Some areas of the UK reported AM cases more commonly. Clinical signs such as recumbency, rectal temperature, distended bladder and serum creatine kinase activity might be useful prognostic indicators though should be considered in the context of the clinical picture. Treatment with vitamins increases odds of survival.

Topics: Acer; Animals; Food Contamination; Horse Diseases; Horses; Hypoglycins; Logistic Models; Multivariate Analysis; Retrospective Studies; Rhabdomyolysis; Risk Factors; Time Factors; United Kingdom