Studies on the Pharmacokinetics and Toxicopathy of Diacetoxyscirpenol and Deoxynivalenol in Swine, Cattle, and Dogs (Anguidine, Nsc-141537, Vomitoxin)
Coppock, Robert Walter
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https://hdl.handle.net/2142/71316
Description
Title
Studies on the Pharmacokinetics and Toxicopathy of Diacetoxyscirpenol and Deoxynivalenol in Swine, Cattle, and Dogs (Anguidine, Nsc-141537, Vomitoxin)
Author(s)
Coppock, Robert Walter
Issue Date
1984
Department of Study
Veterinary Medical Science
Discipline
Veterinary Medical Science
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Agriculture, Animal Pathology
Abstract
In these studies, swine were dosed with diacetoxyscirpenol (DAS) at 0.1, 0.5, and 1.0 mg/kg and deoxynivalenol (DON) at 0.5 mg/kg, whereas cattle and dogs were dosed with DAS at 0.5 mg/kg.
The pharmacokinetics of DAS (swine and cattle) and DON (swine) were monitored. Diacetoxyscirpenol was found to have a large V(,d) and total body clearance which suggested that it was widely distributed to and metabolized in the peripheral as well as the central compartment. Less than 1 percent of the dose of DAS was recovered in the urine of both species. High concentration of monoacetoxyscirpenol and scirpentriol were found in the plasma and urine suggesting that hepatic deacetylation of DAS is an important route of DAS biotransformation. Residues of DAS were found in skeletal muscle, liver, kidney, and lymphoid tissues at 8 hours following dosing. The T(, 1/2) of DON in plasma ranged from 2.0 to 3.7 hours and the 24-hour urinary excretion of DON ranged from 28.1 to 57.2 percent of the dose. Deoxynivalenol was both secreted and reabsorbed by the renal tubules. Residues of DON were not found in skeletal muscle 24 hours following dosing.
Diacetoxyscirpenol was destructive of proliferative and metabolically active tissues. Enterocytes in different anatomical regions of the bowel had differing susceptibilities to DAS. Diacetoxyscirpenol was preferentially more cytotoxic to B-lymphocytes as compred to T-lymphocytes. Diacetoxyscirpenol was cytotoxic to specialized ion pumps; namely, renal tubular, gastric parietal, and salivary ductular cells. Endothelial necrosis and hemorrhage were observed in the brain. Pancreatic acinar and islet cellular necrosis were observed in the DAS and DON-treated pigs.
Following exposure to DAS, hematologic changes were observed in swine, dogs, and cattle. These changes included marked disruption of granulocyte and lymphocyte kinetics. Bone marrow damage was observed in the DAS treated animals.
Changes in blood glucose were observed in all of the pigs dosed with DAS and DON, suggesting that under field conditions changes in intermediary metabolism appear to be an important aspect of the toxicity of the 12,13-epoxytrichothecenes.
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