Methylenecyclopropylglycine and hypoglycin A intoxication in three Pére David's Deers (<i>Elaphurus davidianus</i>) with atypical myopathy

Bochnia, Mandy; Ziemssen, Eva; Sander, Johannes; Stief, Birgit; Zeyner, Annette

doi:10.1002/vms3.406

Cited by 11 publications

(18 citation statements)

References 24 publications

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“…Methylenecyclopropylglycine (MCPrG), a lower homologue of HGA, was also linked to suspected cases of hypoglycemic encephalopathy, similar to Jamaican vomiting disease in humans [13] as well as to AM cases in horses [14]. In ruminants, AM cases were reported for captured David's deer (Elaphurus davidianus) after ingestion of huge quantities of seeds and seedlings [15] as well as leaves and branches [16], respectively, from pruned maple trees. The presence of MCPrG and metabolites of HGA and MCPrG in the kidney and liver of dead David's deer [16] and HGA in the muscle [17] and hair [18] of affected horses (MCPrG and its metabolites are not investigated in this study), might serve as evidence for the possibility of SM toxin transfer from feed into the tissues of both horses and ruminants.…”

Section: Introductionmentioning

confidence: 99%

“…In ruminants, AM cases were reported for captured David's deer (Elaphurus davidianus) after ingestion of huge quantities of seeds and seedlings [15] as well as leaves and branches [16], respectively, from pruned maple trees. The presence of MCPrG and metabolites of HGA and MCPrG in the kidney and liver of dead David's deer [16] and HGA in the muscle [17] and hair [18] of affected horses (MCPrG and its metabolites are not investigated in this study), might serve as evidence for the possibility of SM toxin transfer from feed into the tissues of both horses and ruminants. This is in line with in vitro results showing that HGA is remarkably resistant during inoculation to equine gastric [19] as well as bovine [20] and ovine rumen content [19], and thus potentially available for absorption.…”

Section: Introductionmentioning

confidence: 99%

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Hypoglycin A in Cow’s Milk—A Pilot Study

Bochnia

Ziegler

Glatter

et al. 2021

Toxins

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Hypoglycin A (HGA) originating from soapberry fruits (litchi, and ackee) seeds or seedlings from the sycamore maple (SM) tree (related to Sapindaceae) may cause Jamaican vomiting sickness in humans and atypical myopathy in horses and ruminants. A possible transfer into dairy cow’s milk cannot be ruled out since the literature has revealed HGA in the milk of mares and in the offal of captured deer following HGA intoxication. From a study, carried out for another purpose, bulk raw milk samples from four randomly selected dairy farms were available. The cows were pastured in the daytime. A sycamore maple tree was found on the pasture of farm No. 1 only. Bulk milk from the individual tank or milk filling station was sampled in parallels and analyzed for HGA by LC-ESI-MS/MS. Measurable concentrations of HGA occurred only in milk from farm No. 1 and amounted to 120 and 489 nmol/L. Despite low and very variable HGA concentrations, the results indicate that the ingested toxin, once eaten, is transferred into the milk. However, it is unknown how much HGA the individual cow ingested during grazing and what amount was transferred into the bulk milk samples. As a prerequisite for a possible future safety assessment, carry-over studies are needed. Furthermore, the toxins’ stability during milk processing should also be investigated as well.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoglycin A in Cow’s Milk—A Pilot Study

Bochnia

Ziegler

Glatter

et al. 2021

Toxins

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“…These amino acids are abundantly formed in some plants of the family Sapindaceae such as lychee and ackee (especially in unripe fruits) [ 2 – 6 ] as well as in the seeds, leaves and seedlings/young shoots of some maple trees ( Acer species) including sycamore maple ( Acer pseudoplatanus ) [ 7 – 11 ] and box elder maple ( Acer negundo ) [ 11 , 12 ]. HGA and MCPrG are known to be toxic to many species, and their consumption has been associated with outbreaks of potentially fatal diseases such as hypoglycemic encephalopathy [ 13 , 14 ] and Jamaican vomiting sickness [ 15 – 19 ] in humans and atypical myopathy in horses [ 20 – 24 ] and deers [ 25 , 26 ]. Maple trees are especially abundant in central Europe and the USA, which may pose a risk of animal intoxication following ingestion of maple seeds and seedlings.…”

Section: Introductionmentioning

confidence: 99%

A sensitive LC–MS/MS method for the quantification of the plant toxins hypoglycin A and methylenecyclopropylglycine and their metabolites in cow’s milk and urine and application to farm milk samples from Germany

2023

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Hypoglycin A (HGA) and its homologue methylenecyclopropylglycine (MCPrG) are present in ackee and lychee as well as seeds, leaves, and seedlings of some maple (Acer) species. They are toxic to some animal species and humans. The determination of HGA, MCPrG, and their glycine and carnitine metabolites in blood and urine is a useful tool for screening for potential exposure to these toxins. In addition, HGA, MCPrG, and/or their metabolites have been detected in milk. In this work, simple and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) methods without derivatization were developed and validated for the quantification of HGA, MCPrG, and their metabolites in cow’s milk and urine. An extraction procedure from milk samples has been developed, whereas a dilute-and-shoot approach was implemented for urine samples. For quantification, the MS/MS analysis was performed in multiple reaction monitoring mode. The methods were validated according to the European Union guidelines using blank raw milk and urine as matrices. The limit of quantification presented here for HGA in milk (1.12 µg/L) is noticeably lower than the lowest published limit of detection (9 µg/L). Acceptable values for recovery (89–106% and 85–104% in milk and urine, respectively) and precision (≤ 20%) were obtained for all the quality control levels. The stability of HGA and MCPrG in frozen milk over a period of 40 weeks has been demonstrated. The method was applied to 68 milk samples from 35 commercial dairy farms and showed the absence of any quantifiable amounts of HGA, MCPrG, and their metabolites. Graphical Abstract

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“…However, to our knowledge, there is neither a direct proof that dairy cows ingest sycamore seedlings nor are there data on metabolism and excretion of maple toxins by dairy cows available. For ruminants in general, toxic effects caused by HGA/MCPrG have only been demonstrated in the browsing Père David’s deer, gnus, and Bactrian camels, − while there are no known cases of poisoning in grazers like sheep or intermediate types like goats. , Gonzalez-Medina et al detected HGA in serum samples from ewes and their lambs and also MCPA conjugates in one ewe at 0, 2, and 7 days after grazing on a pasture with sycamore seedlings. No animal in this case showed any adverse effects, suggesting a low (or even no) sensitivity for the toxins in sheep.…”

Section: Introductionmentioning

confidence: 99%

Detection of Hypoglycin A and MCPrG Metabolites in the Milk and Urine of Pasture Dairy Cows after Intake of Sycamore Seedlings

Engel

El‐Khatib

Klevenhusen

et al. 2023

J. Agric. Food Chem.

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Hypoglycin A (HGA), methylenecyclopropylglycine (MCPrG), hypoglycin B (HGB), and γ-glutamyl-α-(methylenecyclopropyl) glycine (γ-glutamyl-MCPrG) are secondary plant metabolites occurring in sycamore maple (Acer pseudoplatanus) as well as several other Sapindaceae (e.g., Blighia sapida). By interfering with energy metabolism, they may cause severe intoxication in humans and other species. However, to date, there is not enough data available concerning the intake, metabolism, or excretion of sycamore maple toxins in dairy cows. In May 2022, five cows were observed over four days, when they had first access to a pasture with two sycamore maples. Grazing of their seedlings that grew numerously in between the pasture plants was monitored by direct observation. Milk samples were drawn both from individual cows and from the bulk tank. Spontaneous urine samples were collected from all cows on day 3 after access to the pasture. Seedlings (100 g) were sampled on the pasture and analyzed, together with milk and urine samples, for sycamore toxins and their metabolites using liquid chromatography− tandem mass spectrometry and liquid chromatography-high-resolution mass spectrometry. Cows ingested sycamore seedlings while grazing. Values of HGA in milk were below the limit of quantification. However, metabolites of HGA and MCPrG were detected in individual milk samples already at the end of the first day of grazing. Urine samples of all five cows showed higher concentrations of conjugated HGA and MCPrG metabolites than in milk. Observations suggest that dairy cows may have a low susceptibility toward sycamore maple toxins. However, whether this could be attributed to foregut fermenting species in general requires further elucidation.

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Methylenecyclopropylglycine and hypoglycin A intoxication in three Pére David's Deers (Elaphurus davidianus) with atypical myopathy

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 11 publications

References 24 publications

Hypoglycin A in Cow’s Milk—A Pilot Study

Hypoglycin A in Cow’s Milk—A Pilot Study

A sensitive LC–MS/MS method for the quantification of the plant toxins hypoglycin A and methylenecyclopropylglycine and their metabolites in cow’s milk and urine and application to farm milk samples from Germany

Detection of Hypoglycin A and MCPrG Metabolites in the Milk and Urine of Pasture Dairy Cows after Intake of Sycamore Seedlings

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