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Development of an L6 myoblast in vitro model of moniliformin toxicosis

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Abstract

L6 myoblasts were used as an in vitro model to investigate the role of moniliformin and its interaction with monensin in turkey knockdown syndrome and sudden death syndromes in poultry. Cell viability and microscopic and ultrastructural alterations noted in L6 myoblasts cultured in the presence of moniliformin (0.0–0.3 μg/μl) were compared to those observed in parallel cultures also containing one of the following compounds: selenium (0–0.004 ng/μl), thiamine (0–0.3 μg/μl), or pyruvate (0–0.46 μg/μl). Marked dilation of the RER, membranous whorls, glycogen deposition, membrane-bound cytoplasmic inclusions and necrosis were observed in myoblasts exposed to 0.03/2-0.30 μg moniliformin/μl medium. Supplementation of medium with thiamine and pyruvate, or selenium, provided significant protection to cells exposed to 0.0–0.3 μg/μl or 0.0–0.15 μg moniliformin/μl, respectively. Dose-dependent differences in protein and ATP production were not detected. Myoblasts grown in medium containing 0–0.15 μg moniliformin/μl and 7.5–50.0 μM A23187, beauvericin or monensin had degrees of cytotoxicity similar to parallel cultures receiving only an ionophore. L6 myoblasts were a useful model of moniliformin toxicosis. The findings of this study suggest cytotoxicity due to moniliformin in L6 myoblasts may be due in part to oxidative damage and altered pyruvate metabolism, and that moniliformin does not predispose myoblasts to ionophore toxicosis. This study supports the results of in vivo investigations in poultry that moniliformin and monensin do not act synergistically to induce knockdown or monensin toxicosis.

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References

  1. Abbas HK, Mirocha CJ, Vesonder RF, Gunther R. Acute toxic effects of an isolate of moniliformin-producing Fusarium oxysporum and purified moniliformin on rats. Arch Environ Contam Toxicol 1990; 19: 433–436.

    Article  CAS  PubMed  Google Scholar 

  2. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. The plasma membrane. In: Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (eds). The Cell. New York, NY: Garland Publishing, Inc., 1989: 275–340.

    Google Scholar 

  3. Blass JP, Kark RAP, Engel WK. Clinical studies of a patient with pyruvate decarboxylase deficiency. Arch Neurol 1971; 25: 449–460.

    CAS  PubMed  Google Scholar 

  4. Burka LT, Doran J, Wilson BJ. Enzyme inhibition and the toxic action of moniliformin and other vinylogous a ketoacids. Biochem Pharmacol 1982; 31: 79–84.

    Article  CAS  PubMed  Google Scholar 

  5. Burmeister HR, Ciegler A, Vesonder RF. Moniliformin, a metabolite of Fusarium moniliforme NRRL 6322: Purification and toxicity. Appl Environ Microbiol 1979; 37: 11–13.

    CAS  PubMed  Google Scholar 

  6. Burmeister HR, Grove MD, Kwolek WF. Moniliformin and butenolide: Effect on mice of high-level, long-term oral intake. Appl Environ Microbiol 1980; 40: 1142–1144.

    CAS  PubMed  Google Scholar 

  7. Cardona CJ, Galey FD, Bickford AA, Charlton BR, Cooper GL. Skeletal muscle myopathy produced with experimental dosing of turkeys with monensin. Avian Dis 1993; 37: 107–117.

    Article  CAS  PubMed  Google Scholar 

  8. Chen L, Tian X, Yang B. A study on the inhibition of rat myocardium glutathione peroxidase and glutathione reductase by moniliformin. Mycopathologia 1990; 110: 119–124.

    Article  CAS  PubMed  Google Scholar 

  9. Cheville NF. Blockade of metabolic pathways. In: Cheville NF (ed.), Ultrastructural pathology. Ames, Iowa: Iowa State University Press. 1994: 126–191.

    Google Scholar 

  10. Cheville NF. Interpretation of acute cellular injury and degeneration. In: Cheville NF (ed), Ultrastructural patholog. Ames, Iowa: Iowa State University Press, 1994: 51–76.

    Google Scholar 

  11. Cole RJ, Kirksey JW, Cutler HG, Doupnik BL, Peckham JC. Toxin from Fusarium moniliforme: effects on plants and animals. Science 1973; 179: 1324–1326.

    Article  CAS  PubMed  Google Scholar 

  12. Dawson M. Initiation and maintenance of cultures. In: Butler M, Dawson M (eds), Cell Culture. Oxford, UK: Bios Scientific Publishers Limited, 1992: 25–42.

    Google Scholar 

  13. DeVivo DC. The expanding clinical spectrum of mitochondrial disease. Brain Develop 1993; 15: 1–22.

    Article  CAS  Google Scholar 

  14. Deyu Z, Qi F, Xianghzen Y, Chenghe L, Yan P, Qin C. Ultrastructural study of moniliformin induced lesions of myocardium in rats and mice. Biomed Environ Sci 1993; 6: 37–44.

    Google Scholar 

  15. DuBourdieu DJ, Shier WT. Sodium- and calcium-dependent steps in the mechanism of neonatal rat cardiac myocyte killing by ionophores. II. The calcium-carrying ionophore, A23187. Toxicol Appl Pharmacol 1992; 116: 47–56.

    Article  CAS  PubMed  Google Scholar 

  16. Emeteria Y, Roddy F, Yount RG, Metzler DE. The catalytic decarboxylation of pyruvate by thiamine. J Biol Chem 1958; 234: 733–737.

    Google Scholar 

  17. Engelhardt JA, Carlton WW, Tuite JF. Toxicity of Fusarium moniliforme var. subglutinans in chicks, ducklings and turkey poults. Avian Dis 1989; 33: 357–360.

    Article  CAS  PubMed  Google Scholar 

  18. Frank RK, Newman J, Ruth GR. Lesions of perirenal hemorrhagic syndrome in growing turkeys. Avian Dis 1991; 35: 523–534.

    Article  CAS  PubMed  Google Scholar 

  19. Gathercole PS, Thiel PG, Hofmeyr JHS. Inhibition of pyruvate dehydrogenase complex by moniliformin. Biochem J 1986; 233: 719–723.

    CAS  PubMed  Google Scholar 

  20. Jeffrey JS, Croual R, Meteyer CU, Galey FD, Kinde H, Medina H. Recurrent transient paresis in a turkey flock. Avian Dis 1992; 36: 760–765.

    Article  CAS  PubMed  Google Scholar 

  21. Joffe AZ. Fusariotoxicoses in laboratory animals. In: Fusarium species: their biology and toxicology. New York: John Wiley and Sons, 1986: pp. 300–344.

    Google Scholar 

  22. Joffe AZ. Principal toxins produced by Fusarium sp. In: Fusarium Species: Their Biology and Toxicology. New York: John Wiley and Sons, 1986: 79–163.

    Google Scholar 

  23. Joffe AZ. Toxic Fusarium species and varieties in nature and in laboratory conditions. In: Fusarium Species: Their Biology and Toxicology. New York: John Wiley and Sons, 1986: 9–24.

    Google Scholar 

  24. Kriek NPJ, Marasas WFO, Steyn PS, van Rensburg SJ, Steyn M. Toxicity of a moniliformin-producing strain of Fusarium moniliforme var. subglutinans isolated from maize. Fd Cosmet Toxicol 1977; 15: 578–587.

    Article  Google Scholar 

  25. Laska DA, Williams PD, Reboulet JT, Morris RW. The L6 muscle cell line as a tool to evaluate parenteral products for irritation. J Parenter Sci Technol 1991; 45: 77–82.

    CAS  PubMed  Google Scholar 

  26. Ledoux DR, Bermudez AJ, Rottinghaus GE, Broomhead J, Bennett GA. Effects of feeding Fusarium fujikuroi culture material, containing known levels of moniliformin, in young broiler chicks. Poultry Sci 1995; 74: 297–305.

    CAS  Google Scholar 

  27. Novilla MN. The veterinary importance of the toxic syndrome induced by ionophores. Vet Hum Toxicol 1992; 34: 66–70.

    CAS  PubMed  Google Scholar 

  28. Norred WP, Bacon CW, Porter JK, Voss KA. Inhibition of protein synthesis in rat primary hepatocytes by extracts of Fusarium moniliforme-contaminated corn. Fd Chem Toxciol 1990; 28: 89–94.

    Article  CAS  Google Scholar 

  29. Passonneau JV, Lowry OH. A collection of metabolite assays. In: Enzymatic analysis. Totowa, NJ: Humana Press. 1993; 111–228.

    Google Scholar 

  30. Rabie CJ, Marasas WFO, Thiel PG, Lubben A, Vleggaar R. Moniliformin production and toxicity of different Fusarium species from southern Africa. Appl Environ Microbiol 1982; 43: 517–521.

    CAS  PubMed  Google Scholar 

  31. Shier WT, DuBourdieu DJ. Sodium- and calcium-dependent steps in the mechanism of neonatal rat cardiac myocyte killing by ionophores. I. The sodium-carrying ionophore, monensin. Toxicol Appl Pharmacol 1992; 116: 38–46.

    Article  CAS  PubMed  Google Scholar 

  32. Slauson DO, Cooper BJ. Disease at the cellular level. In: Pine JW, Napora L (eds), Mechanisms of disease, 2nd ed. Baltimore, MD: Williams and Wilkings, 1990: 19–88.

    Google Scholar 

  33. Squires EF, Summers JD. A consideration of comparative metabolic aspects of the aetiology of sudden death syndrome and ascites in broilers. Br Vet J 1993; 149: 285–294.

    CAS  PubMed  Google Scholar 

  34. Thiel PG. A molecular mechanism for the toxic action of moniliformin, a mycotoxin produced by Fusarium moniliforme. Biochem Pharmacol 1978; 27: 483–486.

    Article  CAS  PubMed  Google Scholar 

  35. Vesonder RF, Gasdorf H, Peterson RE. Comparison of the cytotoxicities of Fusarium metabolites and Alternaria metabolite AAL-Toxin to cultured mammalian cell lines. Arch Environ Contam Toxicol 1993; 24: 473–477.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang H, Li JL. Mechanism of toxicity of moniliformin. Proc Japn Assoc Mycotox 1988; Suppl. 1: 109–110.

    Google Scholar 

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Authors and Affiliations

  1. Dept. of Veterinary Pathobiology and the Animal Disease Diagnostic Laboratory, Purdue University, 47907, West Lafayette, IN

    R. Reams, H. L. Thacker & D. Harrington

  2. Dept. of Pharmacology and Toxicology, Purdue University, 47907, West Lafayette, IN

    W. Greenlee

  3. Eli Lilly and Company, 46140, Greenfield, IN

    M. Novilla, D. Laska & J. Horn

  4. USDA, NCAUR, ARS, 61604, Peoria, IL, USA

    R. Vesonder

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  1. R. Reams
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  2. H. L. Thacker
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  3. M. Novilla
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  4. D. Laska
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  7. W. Greenlee
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  8. R. Vesonder
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Reams, R., Thacker, H.L., Novilla, M. et al. Development of an L6 myoblast in vitro model of moniliformin toxicosis. Mycopathologia 133, 105–114 (1996). https://doi.org/10.1007/BF00439121

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  • DOI: https://doi.org/10.1007/BF00439121

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