A clinical, histological and ultrastructural study of the toxic effects of Imidocarb dipropionate in goats : a dissertation /
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| Other Authors: | , |
| Format: | Thesis Book |
| Language: | English |
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[College Station, Tex.] :
[Texas A&M University],
[1974]
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| Abstract: | ABSTRACT: The toxic effects of Imidocarb dipropionate were studied in adult Angora goats following the intramuscular injection of a lethal dosage of the drug. The acute clinical signs of toxicosis were transient and included excessive salivation and diarrhea which were attributed to an apparent anticholinesterase activity of the drug. The severe clinical signs of toxicosis to include dyspnea, anorexia and inactivity were observed on days 4 to 8 post-injection (PI) during which time 7 of the goats died and 4 moribund goats were euthanatized. Associated with the severe signs of toxicosis were 1) renal lesions; 2) significant increases in the mean serum urea nitrogen concentrations and serum glutamic oxalacetic transaminase activity; and 3) significant increases in the number of neutrophils. Gross renal lesions included an increase in the size of the kidneys and the presence of alternating white and red streaks radiating from the renal medulla to the cortex. Other gross lesions included pulmonary congestion and edema and excessive fluid in the pleural and peritoneal cavities. Histological lesions in the kidneys progressed rapidly from pyknosis and karyorrhexis of the tubular epithelial nuclei observed at 6 and 12 hours PI to severe acute tubular necrosis of the proximal convoluted tubules on days 1 and 2 PI. The ultrastructural changes in the kidney corresponded with those observed histologically and were confined predominately to the epithelial cells of the proximal convoluted tubules. The ultrastructural changes observed at 3 hours PI included: disruption of the plasma membrane; dilation and proliferation of the endoplasmic reticulum; swollen electron dense mitochondria; and rarefaction of the cytoplasmic ground substance. The early ultrastructural changes probably resulted from the loss of membrane permeability with the subsequent influx of water into the cell. Rarefaction of the cytoplasmic ground substance and the dilation and proliferation of the endoplasmic reticulum resulting in the formation of numerous vesicular structures progressed rapidly from 3 to 12 hours PI. Complete disruption of the plasma membrane with fragmentation of the microvilli, loss of junctional complexes and cellular disjuntion was evident in most proximal tubular epithelial cells by 12 hours PI. Changes in mitochondrial configuration and volume continued with the formation of single or double membrane bounded structures containing fragmented cristae and clear vacuoles. Foci of electron dense, amorphous, flocculent material were first observed within the degenerating mitochondria at 6 hours PI. The foci of intramitochondrial flocculent material probably represented denatured, clumped, metrical protein. A second type of electron dense deposit was observed within the mitochondria and in the cytoplasm on day 1 PI and may have represented the formation of a calcium-protein complex and an early stage of clacificaiton. A moderate increase in the number of cytosomes occurred within the tubular epithelial cells. The basement membrane of the proximal convoluted tubules remained intact and provided support for regenerating epithelial cells. The ultrastructural and histological hepatic alterations observed were considered to be reversible, and were attributed to the mild hepatotoxic action of Imidocarb dipropionate. Gross and histological lesions were first observed in the respiratory system on day 4 PI and were attributed to renal failure and uremia rather than to the direct toxic action of Imidocarb dipropionate. Progressive decreases were observed in renal cortical succinic dehydrogenase and in ATPase activity beginning at 12 hours and on day 1 PI respectively. The occurrence of ultrastructural and histological changes prior to the decreases in enzymatic activity indicated the decrease in enzymatic activity was secondary to cellular injury. The loss of ability of the epithelial cells of the proximal convoluted tubules to regulate cellular volume was considered to be the initial event responsible for the subsequent ultrastructural, histological and histochemical changes observed following the injection of Imidocarb dipropionate. |
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| Item Description: | Vita. "Major Subject: Veterinary Pathology". "Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement for the degree of Doctor of Philosophy August 1974." |
| Physical Description: | xvi, 165 leaves : illustrations ; 28 cm |
| Bibliography: | Includes bibliographical references. |