Plasma ferulenol concentration and activity of clotting factors in sheep with Ferula communis variety brevifolia intoxication

Noursaid Tligui From the Department of Veterinary Pathology, Agronomique et Veterinaire Hassan I, I BP. 6202, Rabat, Morocco Institut (Tligui), and the Department of Veterinary Diagnostic Medicine College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108 (Ruth, Felice).

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George R. Ruth From the Department of Veterinary Pathology, Agronomique et Veterinaire Hassan I, I BP. 6202, Rabat, Morocco Institut (Tligui), and the Department of Veterinary Diagnostic Medicine College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108 (Ruth, Felice).

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Lawrence J. Felice From the Department of Veterinary Pathology, Agronomique et Veterinaire Hassan I, I BP. 6202, Rabat, Morocco Institut (Tligui), and the Department of Veterinary Diagnostic Medicine College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108 (Ruth, Felice).

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Summary

Dynamics of plasma ferulenol concentration and its effect on the vitamin K-dependent coagulation factors, prothrombin time (pt), and activated partial thromboplastin time (aptt) were determined in 4 sheep intoxicated individually with 600 g of powdered Ferula communis variety brevifolia (fcb) given in 8 doses at intervals of 6 hours. Ferulenol was detected in the plasma of all sheep at initial blood sample collection, 6 hours after the first dose of approximately 75 g of fcb was placed in the rumen. The last observed peak of approximately 20 μg/ml was detected at about 12 hours after the last of 8 doses, and the mean concentration then decreased to < 1 μg/ml during the next 70 hours. Maximal concentration of ferulenol and time for plasma clearance varied with individual sheep. The pt increased steadily to a maximum of 6 times normal about 70 hours after the last peak plasma ferulenol concentration and about 80 hours after fcb administration was stopped. The pt then returned to almost normal (ratio of 1.12) from the maximum (ratio of 6.12) within approximately 5 days. The aptt results generally paralleled the pt results, but the change was not as marked. Maximal pt and aptt ratios were animal - dependent and not always related to plasma ferulenol concentration. The activity of all the vitamin K-dependent coagulation factors was depressed, but the variations were unique to each factor. Factor V, a vitamin K-independent coagulation factor actually had a brief period of increased plasma activity. We concluded that the effects on P, T aptt, and vitamin K-dependent coagulation factors induced in sheep intoxicated with fcb were consistent with the coumarinic structure of ferulenol, the intoxicating compound in fcb, which seems to have a short-term anticoagulation effect.

Summary

Dynamics of plasma ferulenol concentration and its effect on the vitamin K-dependent coagulation factors, prothrombin time (pt), and activated partial thromboplastin time (aptt) were determined in 4 sheep intoxicated individually with 600 g of powdered Ferula communis variety brevifolia (fcb) given in 8 doses at intervals of 6 hours. Ferulenol was detected in the plasma of all sheep at initial blood sample collection, 6 hours after the first dose of approximately 75 g of fcb was placed in the rumen. The last observed peak of approximately 20 μg/ml was detected at about 12 hours after the last of 8 doses, and the mean concentration then decreased to < 1 μg/ml during the next 70 hours. Maximal concentration of ferulenol and time for plasma clearance varied with individual sheep. The pt increased steadily to a maximum of 6 times normal about 70 hours after the last peak plasma ferulenol concentration and about 80 hours after fcb administration was stopped. The pt then returned to almost normal (ratio of 1.12) from the maximum (ratio of 6.12) within approximately 5 days. The aptt results generally paralleled the pt results, but the change was not as marked. Maximal pt and aptt ratios were animal - dependent and not always related to plasma ferulenol concentration. The activity of all the vitamin K-dependent coagulation factors was depressed, but the variations were unique to each factor. Factor V, a vitamin K-independent coagulation factor actually had a brief period of increased plasma activity. We concluded that the effects on P, T aptt, and vitamin K-dependent coagulation factors induced in sheep intoxicated with fcb were consistent with the coumarinic structure of ferulenol, the intoxicating compound in fcb, which seems to have a short-term anticoagulation effect.

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