Pyrrolizidine alkaloid-induced liver disease in horses: an early diagnosis.
Abstract: Nine adult horses were fed alfalfa hay cubes containing approximately 10% Senecio vulgaris until all horses had consumed approximately the same amount of toxic components of S vulgaris, pyrrolizidine alkaloids (PA). The amount of PA consumed was determined by the amount that induced clinical signs of PA toxicosis in 3 horses. The 6 other horses were given similar amounts per kilogram of body weight. An initial decrease of feed intake was observed when horses' diets were changed from alfalfa cubes to alfalfa/Senecio cubes, and feed intake was decreased further over 89 to 98 days. From 50 to 159 days, body weight decreased in all horses. Liver disease was induced in all 9 horses after they ate an average of 233 +/- 9.2 mg of PA/kg of body weight. Eight horses died or were euthanatized. Treatment with branched chain amino acids had no effect on mortality, but appeared to reduce neurologic problems. Clinical signs of PA-induced liver disease included ataxia, head pressing, and decreased feed intake. Other clinical signs of toxicosis were observed individual horses, but did not develop in most horses. Megalocytic hepatopathy developed. Liver abnormalities proceeded as PA was consumed and were severe in 8 of 9 horses before clinical signs of toxicosis appeared. Sulfobromophthalein sodium clearance did not decrease until PA-induced liver disease was advanced. Bile acid (BA) concentrations increased to greater than or equal to 50 mumol/L, in the 8 horses that died. One horse had hepatopathy and increased BA concentration, but survived. In this horse, BA concentration peaked at 33 mumol/L and then decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1988-04-01 PubMed ID: 3377320
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- Journal Article
Summary
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The research discusses the impact of pyrrolizidine alkaloids (PA) found in Senecio vulgaris on horses’ liver health, through an experiment where nine adult horses were fed alfalfa hay cubes containing the toxic component. All subjects showed significant liver disease, with most developing severe complications and eight dying or being euthanized. The study notably demonstrates that early signs in the form of dietary changes and weight loss appear before clinical signs of the resulting liver disease.
Study Setup
- The study involved nine adult horses being fed alfalfa hay cubes, containing about 10% of Senecio vulgaris, a plant species known for containing poisonous pyrrolizidine alkaloids (PA).
- The dosage of PA was established by a preliminary toxicosis approximation, where the amount that caused visible clinical symptoms in three horses was considered reference.
- This dosage was then adjusted according to each horse’s weight. Essentially, all horses consumed nearly the same amount of PA per kilogram of their body weight.
Resulting Dietary Changes and Weight Loss
- As soon as the horses’ diets were switched to the contaminated feed, a drop in feed intake was observed.
- This reduction in diet continued between 89 to 98 days of the experiment.
- All the horses experienced a decrease in body weight between 50 to 159 days, marking a significant directional change regarding their health status.
Liver Disease Development
- All nine horses developed liver disease after consuming an average of about 233 mg of PA/kg body weight.
- Initial indications of liver disease were ataxia (loss of control over body movements), decreased feed intake, and head pressing.
- Upon examination, megalocytic hepatopathy (an enlarged liver condition) was detected in the horses.
- The severity of liver abnormalities increased as more PA was consumed, and in most cases, these liver issues were significantly advanced before the appearance of the clinical signs of toxicity.
Mortality
- Eight of the nine horses either died naturally or had to be euthanized due to extreme suffering, indicating a high mortality rate from the intake of PA.
- No positive impact on survival was observed from treatment with branched-chain amino acids, although it appeared to reduce some neurological symptoms.
- Bile Acid (BA) concentrations in eight horses that died increased significantly. However, one horse, which developed hepatopathy and increased BA concentration, managed to survive with its BA concentration peaking at 33 mumol/L, before gradually reducing.
- The removal of a liver-detoxifying agent, sulfobromophthalein sodium, was not significantly impaired until the stage of advanced liver disease.
Cite This Article
APA
Mendel VE, Witt MR, Gitchell BS, Gribble DN, Rogers QR, Segall HJ, Knight HD.
(1988).
Pyrrolizidine alkaloid-induced liver disease in horses: an early diagnosis.
Am J Vet Res, 49(4), 572-578.
Publication
Researcher Affiliations
- Department of Animal Science, School of Veterinary Medicine, University of California, Davis 95616.
MeSH Terms
- Amino Acids, Branched-Chain / therapeutic use
- Animal Feed
- Animals
- Bile Acids and Salts / blood
- Body Weight
- Chemical and Drug Induced Liver Injury
- Eating
- Female
- Horse Diseases / chemically induced
- Horse Diseases / diagnosis
- Horse Diseases / drug therapy
- Horses
- Liver / pathology
- Liver Diseases / diagnosis
- Liver Diseases / drug therapy
- Liver Diseases / veterinary
- Liver Function Tests / veterinary
- Male
- Plants, Toxic
- Pyrrolizidine Alkaloids / toxicity
- Regression Analysis
- Senecio
- Sulfobromophthalein
Citations
This article has been cited 10 times.- Kopecka A, Novotna T, Svobodova Z, Drabkova Z. Senecio ovatus poisoning in a horse - A case report. Vet Med (Praha) 2024 Sep;69(9):329-336.
- Xiong A, Lu L, Jiang K, Wang X, Chen Y, Wang X, Zhang W, Zhuge Y, Huang W, Li L, Liao Q, Yang F, Liu P, Ding L, Wang Z, Yang L. Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Arch Toxicol 2024 Aug;98(8):2557-2576.
- Câmara ACL, de Sousa Argenta VL, de Moraes DDA, Fonseca EF, Fino TCM, Paludo GR, Soto-Blanco B. Hematological and Serum Biochemical Changes and Their Prognostic Value in Horses Spontaneously Poisoned by Crotalaria spectabilis. Front Vet Sci 2021;8:741530.
- Sroka L, Müller C, Hass ML, These A, Aboling S, Vervuert I. Horses' rejection behaviour towards the presence of Senecio jacobaea L. in hay. BMC Vet Res 2022 Jan 7;18(1):25.
- Waizenegger J, Glück J, Henricsson M, Luckert C, Braeuning A, Hessel-Pras S. Pyrrolizidine Alkaloids Disturb Bile Acid Homeostasis in the Human Hepatoma Cell Line HepaRG. Foods 2021 Jan 14;10(1).
- Quan NV, Dang Xuan T, Teschke R. Potential Hepatotoxins Found in Herbal Medicinal Products: A Systematic Review. Int J Mol Sci 2020 Jul 16;21(14).
- Xiong A, Yang F, Fang L, Yang L, He Y, Wan YJ, Xu Y, Qi M, Wang X, Yu K, Tsim KW, Wang Z. Metabolomic and genomic evidence for compromised bile acid homeostasis by senecionine, a hepatotoxic pyrrolizidine alkaloid. Chem Res Toxicol 2014 May 19;27(5):775-86.
- Moore RE, Knottenbelt D, Matthews JB, Beynon RJ, Whitfield PD. Biomarkers for ragwort poisoning in horses: identification of protein targets. BMC Vet Res 2008 Aug 8;4:30.
- de Lanux-Van Gorder V. Tansy ragwort poisoning in a horse in southern Ontario. Can Vet J 2000 May;41(5):409-10.
- Kaneko JJ, Rudolph WG, Wilson DW, Carlson GP. Bile acid fractionations by high-performance liquid chromatography in equine liver disease. Vet Res Commun 1992;16(3):161-72.
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