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The effects of phenetyl isothiocyanate and benzyl isothiocyanate on acetaminophen metabolism and toxicity in freshly isolated rat hepatocytes in cell suspension / Yulianingsih Benitex

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Identifier	Thesis 1563
Author	Benitex, Yulianingsih
Title	The effects of phenetyl isothiocyanate and benzyl isothiocyanate on acetaminophen metabolism and toxicity in freshly isolated rat hepatocytes in cell suspension / Yulianingsih Benitex
Publisher	Central Connecticut State University
Date	1999
Resource Type	Master's Thesis
Notes	Acetaminophen is extensively used as an analgesic and antipyretic agent, but at high doses it causes liver damage. The major metabolic pathways of acetaminophen are glucuronidation and sulfation. In addition to these pathways, acetaminophen undergoes oxidation by cytochrome P-450 to the reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which, in turn, conjugates with hepatic glutathione. The conjugation of acetaminophen with glutathione represents an important detoxification reaction because NAPQI is a toxic species that could bind to critical nucleophiles such as protein and DNA. Overdoses of acetaminophen cause the glucuronidation and sulfation pathways to be saturated and, as a result, more metabolism to NAPQI occurs. Since the availability of glutathione is limited, excess generation of NAPQI leads to liver damage. Isothiocyanates such as benzyl isothiocyanate (BITC) and phenetyl isothiocyanate (PEITC) alter metabolism of many compounds and can reduce cellular damage. The purpose of the present study is to evaluate the effect of these isothiocyanates on the metabolism and toxicity of acetaminophen in isolated rat hepatocytes. The toxicity of acetaminophen, up to 2mM, was both time and dose-dependent as determined by cell killing and glutathione depletion. The extent of damage was accelerated in ethanol-pretreated hepatocytes compared to those treated by acetaminophen alone. When isolated rat hepatocytes were given PEITC prior to acetaminophen treatment, there was apparent inhibition of cell toxicity. The inhibitory effect of PEITC also exhibited a dose-dependent relationship. BITC was found ineffective in protecting hepatocytes from the toxic effect of acetaminophen. Neither PEITC nor BITC significantly affected the sulfation and glucuronidation pathways of acetaminophen metabolism in isolated rat hepatocytes.
Subject	Acetaminophen -- Toxicity testing Liver cells Toxicology, Experimental
Department	Department of Chemistry and Biochemistry
Advisor	Jones, Carol A.
Type	Text
Digital Format	application/pdf
Language	eng
OCLC number	45223984
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Home The effects of phenetyl isothiocyanate and benzyl isothiocyanate on acetaminophen metabolism and...

The effects of phenetyl isothiocyanate and benzyl isothiocyanate on acetaminophen metabolism and toxicity in freshly isolated rat hepatocytes in cell suspension / Yulianingsih Benitex

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