Development of an L6 myoblast in vitro model of moniliformin toxicosis.
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 microgram/microliter) were compared to those observed in parallel cultures also containing one of the following compounds: selenium (0-0.004 ng/microliter), thiamine (0-0.3 microgram/microliter), or pyruvate (0-0.46 microgram/microliter). Marked dilation of the RER, membranous whorls, glycogen deposition, membrane-bound cytoplasmic inclusions and necrosis were observed in myoblasts exposed to 0.03-0.30 microgram moniliformin/microliter medium. Supplementation of medium with thiamine and pyruvate, or selenium, provided significant protection to cells exposed to 0.0-0.3 microgram/microliter or 0.0-0.15 microgram moniliformin/microliter, respectively. Dose-dependent differences in protein and ATP production were not detected. Myoblasts grown in medium containing 0-0.15 microgram moniliformin/microliter and 7.5-50.0 microM 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.
Reams
R
R
Dept. of Veterinary Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
Thacker
H L
HL
Novilla
M
M
Laska
D
D
Horn
J
J
Harrington
D
D
Greenlee
W
W
Vesonder
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003503:Cyclobutanes / Q000633:toxicity*; D007476:Ionophores / Q000633:toxicity; D008954:Models, Biological; D008985:Monensin / Q000633:toxicity; D009183:Mycotoxins / Q000633:toxicity*; D011201:Poultry Diseases / Q000209:etiology*; D014176:Protein Biosynthesis; D051381:Rats; D014422:Turkeys
D003503:Cyclobutanes; D007476:Ionophores; D009183:Mycotoxins; C008539:moniliformin; D000255:Adenosine Triphosphate; D008985:Monensin