Canine hepatic slices as a model for studying drug toxicity and metabolism /

Bibliographic Details
Main Author: Scott, Maya Millicent, 1974-
Other Authors: Boothe, Dawn M. (Thesis advisor), Safe, Stephen H. (Thesis advisor)
Format: Thesis eBook
Language:English
Published: [College Station, Tex.] : [Texas A&M University], [2006]
Subjects:
Online Access:Link to OAK Trust copy

MARC

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099 |a 2005  |a Dissertation  |a S34 
100 1 |a Scott, Maya Millicent,  |d 1974- 
245 1 0 |a Canine hepatic slices as a model for studying drug toxicity and metabolism /  |c by Maya Millicent Scott. 
264 1 |a [College Station, Tex.] :  |b [Texas A&M University],  |c [2006] 
336 |a text  |b txt  |2 rdacontent 
337 |a computer  |b c  |2 rdamedia 
338 |a online resource  |b cr  |2 rdacarrier 
500 |a "Major Subject: Toxicology" 
500 |a Title from author supplied metadata (automated record created on Sep. 15, 2006.) 
500 |a Vita. 
500 |a Abstract. 
502 |b Ph. D.  |c Texas A&M University  |d 2005. 
504 |a Includes bibliographical references. 
516 |a Text (Dissertation). 
520 3 |a Tissue slices can be made from organs, such as liver, kidney, brain, and heart, and from various species including humans, dogs, non-human primates, rats and mice. It has been demonstrated that human and rat liver slices are viable for up to 2 days, and liver slices have been extensively used as an in vitro method to study hepatic drug metabolism and toxicity in humans. The objective of this study was to determine the utility of canine hepatic slices as an in vitro model for studying drug metabolism and hepatotoxicity in dogs. Canine hepatic slices were incubated in media containing various drugs to determine the hepatotoxicity of the agents and the ability of the slices to metabolize the drugs. The toxicity of phenobarbital, primidone, lidocaine and carprofen to canine hepatic slices was assessed by determining changes in supernatant concentrations of potassium ions and adenosine triphosphate (ATP); histologic lesions were determined as necrosis, extent of vacuolation and severity of vacuolation. Xenobiotic drug metabolizing enzymatic activity was investigated by determining the metabolism of lidocaine to monoethylglycinexylidide (MEGX), and administration of phenobarbital plus primidone was used as a positive control for hepatotoxicity in dogs. The function of drug-metabolizing enzymes was demonstrated by the successful metabolism of lidocaine to MEGX. Carprofen, a drug which causes idiosyncratic hepatic disease in dogs, did not show any hepatotoxicity at concentrations of 10, 50 and 100 [mu]g/ml using potassium ion levels, ATP concentrations and histology as indicators of hepatotoxicity. Slices incubated in media without drug showed no toxicity over 24 hours based on potassium ion and ATP supernatant concentrations while significant increases in histologic lesions were noted at 8, 12 and 24 hours. Canine hepatic slices were a useful model for examining drug metabolism and toxicity for up to 24 hours. 
538 |a Mode of access: World Wide Web. 
538 |a System requirements: World Wide Web access and Adobe Acrobat Reader. 
500 |a Electronic resource. 
650 4 |a Major toxicology. 
653 |a liver slices 
653 |a drug toxicity 
653 |a hepatic slices 
653 |a drug metabolism 
700 1 |a Boothe, Dawn M.,  |e thesis advisor. 
700 1 |a Safe, Stephen H.,  |e thesis advisor. 
856 4 0 |u http://hdl.handle.net/1969.1/3731  |z Link to OAK Trust copy  |t 0 
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952 f f |a Texas A&M University  |b College Station  |c Electronic Resources  |d Available Online  |t 0  |e 2005 Dissertation S34  |g Electronic  |h Other scheme 
998 f f |a 2005 Dissertation S34  |t 0  |l Available Online