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Oxidant-induced damage to equine erythrocytes from exposure to Pistacia atlantica, Pistacia terebinthus, and Pistacia chinensis.

Abstract: Two horses were referred for methemoglobinemia and hemolytic anemia following 5 acute deaths in their herd from an unidentified toxin source. Horses have a greater risk than other mammalian species of developing methemoglobinemia and hemolytic anemia following ingestion of oxidizing toxins, due to deficiencies in the mechanisms that protect against oxidative damage in erythrocytes. Their susceptibility to oxidative erythrocyte damage is evident in the numerous cases of red maple (Acer rubrum) toxicosis. The suspected toxins causing A. rubrum toxicosis are tannic acid, gallic acid, and a metabolite of gallic acid, pyrogallol. These compounds can be found in a variety of plants, posing a risk to equine health. In order to quickly identify toxin sources, 2 rapid in vitro assays were developed to screen plant extracts for the ability to induce methemoglobin formation or cause hemolysis in healthy equine donor erythrocytes. The plant extract screening focused on 3 species of the genus Pistacia: P. atlantica, P. terebinthus, and P. chinensis, which were located in the horse pasture. Extracts of the seeds and leaves of each species induced methemoglobin formation and resulted in hemolysis, with seed extracts having greater potency. The in vitro assays used in the current study provide a useful diagnostic method for the rapid identification of oxidizing agents from unidentified sources. There is no effective treatment for oxidative erythrocyte damage in horses, making rapid identification and removal of the source essential for the prevention of poisoning.
Publication Date: 2014-09-16 PubMed ID: 25227420PubMed Central: PMC5390776DOI: 10.1177/1040638714550183Google Scholar: Lookup
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Summary

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This research investigates oxidizing toxins found in three species of the Pistacia genus – P. atlantica, P. terebinthus, and P. chinensis – that led to fatal anemia and methemoglobinemia in a horse herd. The research identified these toxins using two rapid in vitro assays developed to screen plant extracts.

Background of the Study

  • This study was prompted by the case of two horses that presented with methemoglobinemia and hemolytic anemia following five acute deaths in their herd due to unknown toxins.
  • Horses are especially susceptible to these conditions due to their weak defense mechanisms against oxidative damage in erythrocytes (red blood cells).
  • This vulnerability in horses is evidenced in numerous incidents of red maple toxicosis, an illness caused by ingesting tannic acid, gallic acid, and pyrogallol found in red maple and other plants.

Methodology

  • The researchers developed two in vitro assays to screen plant extracts for any ability to cause methemoglobin formation or induce hemolysis in healthy equine erythrocytes.
  • The extract screening focused on plants found in the horses’ pastures, specifically three species from the Pistacia genus: P. atlantica, P. terebinthus, and P. chinensis.

Findings

  • Extracts from the seeds and leaves of the three Pistacia species induced methemoglobin formation and caused hemolysis in the erythrocytes, with the seed extracts exhibiting greater potency.
  • The assays developed provided a useful method for the quick identification of oxidizing agents from unknown sources, an important tool given there is currently no effective treatment for oxidative erythrocyte damage in horses.
  • The expedient identification and removal of the toxin source become essential for preventing further poisoning.

Conclusion

  • The study successfully highlighted the potential harm caused by Pistacia species to horses and demonstrated an effective way of quickly identifying oxidizing toxins that can lead to methemoglobinemia and hemolytic anemia.
  • The next steps for research may involve the exploration of potential treatments for oxidative erythrocyte damage in horses or developing preventative measures to shield horses from these harmful toxins.

Cite This Article

APA
Walter KM, Moore CE, Bozorgmanesh R, Magdesian KG, Woods LW, Puschner B. (2014). Oxidant-induced damage to equine erythrocytes from exposure to Pistacia atlantica, Pistacia terebinthus, and Pistacia chinensis. J Vet Diagn Invest, 26(6), 821-826. https://doi.org/10.1177/1040638714550183

Publication

ISSN: 1943-4936
NlmUniqueID: 9011490
Country: United States
Language: English
Volume: 26
Issue: 6
Pages: 821-826

Researcher Affiliations

Walter, Kyla M
  • Department of Molecular Biosciences (Walter, Moore, Puschner), School of Veterinary Medicine, University of California, Davis, CAVeterinary Medical Teaching Hospital (Bozorgmanesh), School of Veterinary Medicine, University of California, Davis, CADepartment of Medicine and Epidemiology (Magdesian), School of Veterinary Medicine, University of California, Davis, CACalifornia Animal Health and Food Safety Laboratory System (Puschner, Woods), School of Veterinary Medicine, University of California, Davis, CA.
Moore, Caroline E
  • Department of Molecular Biosciences (Walter, Moore, Puschner), School of Veterinary Medicine, University of California, Davis, CAVeterinary Medical Teaching Hospital (Bozorgmanesh), School of Veterinary Medicine, University of California, Davis, CADepartment of Medicine and Epidemiology (Magdesian), School of Veterinary Medicine, University of California, Davis, CACalifornia Animal Health and Food Safety Laboratory System (Puschner, Woods), School of Veterinary Medicine, University of California, Davis, CA.
Bozorgmanesh, Rana
  • Department of Molecular Biosciences (Walter, Moore, Puschner), School of Veterinary Medicine, University of California, Davis, CAVeterinary Medical Teaching Hospital (Bozorgmanesh), School of Veterinary Medicine, University of California, Davis, CADepartment of Medicine and Epidemiology (Magdesian), School of Veterinary Medicine, University of California, Davis, CACalifornia Animal Health and Food Safety Laboratory System (Puschner, Woods), School of Veterinary Medicine, University of California, Davis, CA.
Magdesian, K Gary
  • Department of Molecular Biosciences (Walter, Moore, Puschner), School of Veterinary Medicine, University of California, Davis, CAVeterinary Medical Teaching Hospital (Bozorgmanesh), School of Veterinary Medicine, University of California, Davis, CADepartment of Medicine and Epidemiology (Magdesian), School of Veterinary Medicine, University of California, Davis, CACalifornia Animal Health and Food Safety Laboratory System (Puschner, Woods), School of Veterinary Medicine, University of California, Davis, CA.
Woods, Leslie W
  • Department of Molecular Biosciences (Walter, Moore, Puschner), School of Veterinary Medicine, University of California, Davis, CAVeterinary Medical Teaching Hospital (Bozorgmanesh), School of Veterinary Medicine, University of California, Davis, CADepartment of Medicine and Epidemiology (Magdesian), School of Veterinary Medicine, University of California, Davis, CACalifornia Animal Health and Food Safety Laboratory System (Puschner, Woods), School of Veterinary Medicine, University of California, Davis, CA.
Puschner, Birgit
  • Department of Molecular Biosciences (Walter, Moore, Puschner), School of Veterinary Medicine, University of California, Davis, CAVeterinary Medical Teaching Hospital (Bozorgmanesh), School of Veterinary Medicine, University of California, Davis, CADepartment of Medicine and Epidemiology (Magdesian), School of Veterinary Medicine, University of California, Davis, CACalifornia Animal Health and Food Safety Laboratory System (Puschner, Woods), School of Veterinary Medicine, University of California, Davis, CA bpuschner@ucdavis.edu.

MeSH Terms

  • Anemia, Hemolytic / chemically induced
  • Anemia, Hemolytic / diagnosis
  • Anemia, Hemolytic / veterinary
  • Animals
  • Erythrocytes / drug effects
  • Horse Diseases / chemically induced
  • Horse Diseases / diagnosis
  • Horses
  • Methemoglobinemia / chemically induced
  • Methemoglobinemia / diagnosis
  • Methemoglobinemia / veterinary
  • Pistacia / chemistry
  • Pistacia / poisoning
  • Plant Extracts / analysis
  • Plant Extracts / poisoning
  • Plant Extracts / toxicity
  • Plant Leaves / chemistry
  • Plant Leaves / poisoning
  • Seeds / chemistry
  • Seeds / poisoning
  • Species Specificity

Grant Funding

  • T32 ES007314 / NIEHS NIH HHS

Conflict of Interest Statement

. The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

This article includes 19 references
  1. Acker JP, M Croteau I, Yi QL. An analysis of the bias in red blood cell hemolysis measurement using several analytical approaches.. Clin Chim Acta 2012 Nov 12;413(21-22):1746-52.
    pubmed: 22750731doi: 10.1016/j.cca.2012.06.028google scholar: lookup
  2. Agar NS, Gruca M, Harley JD. studies on glucose-6-phosphate dehydrogenase, glutathione reductase and regeneration of reduced glutathione in the red blood cells of various mammalian species.. Aust J Exp Biol Med Sci 1974 Aug;52(4):607-14.
    pubmed: 4447499doi: 10.1038/icb.1974.59google scholar: lookup
  3. Agrawal K, Ebel JG, Altier C, Bischoff K. Identification of protoxins and a microbial basis for red maple (Acer rubrum) toxicosis in equines.. J Vet Diagn Invest 2013 Jan;25(1):112-9.
    pubmed: 23242665doi: 10.1177/1040638712468588google scholar: lookup
  4. Al-Saghir MG. Phylogenetic analysis of the genus Pistacia L. (Anacardiaceae) based on morphological data.. Asian J Plant Sci 2010;9:28–35.
  5. Alward A, Corriher CA, Barton MH, Sellon DC, Blikslager AT, Jones SL. Red maple (Acer rubrum) leaf toxicosis in horses: a retrospective study of 32 cases.. J Vet Intern Med 2006 Sep-Oct;20(5):1197-201.
  6. Baskurt OK, Meiselman HJ. Susceptibility of equine erythrocytes to oxidant-induced rheologic alterations.. Am J Vet Res 1999 Oct;60(10):1301-6.
    pubmed: 10791945
  7. Boyer JD, Breeden DC, Brown DL. Isolation, identification, and characterization of compounds from acer rubrum capable of oxidizing equine erythrocytes.. Am J Vet Res 2002 Apr;63(4):604-10.
    pubmed: 11939327doi: 10.2460/ajvr.2002.63.604google scholar: lookup
  8. Bozorgi M, Memariani Z, Mobli M, Salehi Surmaghi MH, Shams-Ardekani MR, Rahimi R. Five Pistacia species (P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus): a review of their traditional uses, phytochemistry, and pharmacology.. ScientificWorldJournal 2013;2013:219815.
    pmc: PMC3876903pubmed: 24453812doi: 10.1155/2013/219815google scholar: lookup
  9. George LW, Divers TJ, Mahaffey EA, Suarez MJ. Heinz body anemia and methemoglobinemia in ponies given red maple (acer rubrum L.) leaves.. Vet Pathol 1982 Sep;19(5):521-33.
    pubmed: 7147611doi: 10.1177/030098588201900507google scholar: lookup
  10. HARBOE M. A method for determination of hemoglobin in plasma by near-ultraviolet spectrophotometry.. Scand J Clin Lab Invest 1959;11:66-70.
    pubmed: 13646603doi: 10.3109/00365515909060410google scholar: lookup
  11. Harvey JW. The erythrocyte: physiology, metabolism, and biochemical disorders.. Clinical biochemistry of domestic animals 6. Academic Press; San Diego, CA: 2008. pp. 173–240.
  12. Harvey JW, Stockham SL, Scott MA, Johnson PJ, Donald JJ, Chandler CJ. Methemoglobinemia and eccentrocytosis in equine erythrocyte flavin adenine dinucleotide deficiency.. Vet Pathol 2003 Nov;40(6):632-42.
    pubmed: 14608016doi: 10.1354/vp.40-6-632google scholar: lookup
  13. Landau S, Azaizeh H, Muklada H, Glasser T, Ungar ED, Baram H, Abbas N, Markovics A. Anthelmintic activity of Pistacia lentiscus foliage in two Middle Eastern breeds of goats differing in their propensity to consume tannin-rich browse.. Vet Parasitol 2010 Oct 29;173(3-4):280-6.
    pubmed: 20705396doi: 10.1016/j.vetpar.2010.07.006google scholar: lookup
  14. Mahaffey E, Smith JE. Species differences in erythrocyte glutathione reduction rates after oxidation with t-butyl hydroperoxide.. Int J Biochem 1975;6:853–854.
  15. Medeiros LO, Nürmberger R Jr, Medeiros LF. The special behavior of equine erythrocytes connected with the methemoglobin regulation.. Comp Biochem Physiol B 1984;78(4):869-71.
    pubmed: 6467915doi: 10.1016/0305-0491(84)90201-3google scholar: lookup
  16. Poppenga RH, Puschner B. Toxicology.. Equine emergencies: treatment and procedures 4. Saunders Elsevier; St. Louis, MO: 2012. pp. 604–605.
  17. Robin H, Harley JD. Regulation of methaemoglobinaemia in horse and human erythrocytes.. Aust J Exp Biol Med Sci 1967 Feb;45(1):77-88.
    pubmed: 4382737doi: 10.1038/icb.1967.4google scholar: lookup
  18. Smith JE, Kiefer S, Lee M. Glutathione reduction and other enzyme activities in equine erythrocytes.. Comp Biochem Physiol B 1972 Oct 15;43(2):413-7.
    pubmed: 4659578doi: 10.1016/0305-0491(72)90301-xgoogle scholar: lookup
  19. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management.. Ann Emerg Med 1999 Nov;34(5):646-56.
    pubmed: 10533013doi: 10.1016/s0196-0644(99)70167-8google scholar: lookup

Citations

This article has been cited 1 times.
  1. Bozorgmanesh R, Magdesian KG, Rhodes DM, Von Dollen KA, Walter KM, Moore CE, Puschner B, Woods LW, Torrisi K, Voss ED. Hemolytic anemia in horses associated with ingestion of Pistacia leaves.. J Vet Intern Med 2015 Jan;29(1):410-3.
    doi: 10.1111/jvim.12532pubmed: 25619527google scholar: lookup