Journal article
Acetaminophen hepatotoxicity: influence of phenobarbital and beta-naphthoflavone treatment in obese and lean Zucker rats
Toxicology and applied pharmacology, Vol.123(2), pp.219-225
12/1993
DOI: 10.1006/taap.1993.1240
PMID: 8248929
Abstract
The effect of phenobarbital (PB) and beta-naphthoflavone (beta-NF) on acetaminophen (APAP)-induced hepatotoxicity was evaluated in obese and lean Zucker rats. In addition, the consequences of APAP overdose on hepatic CYP2B1/2B2 enzyme activities following PB treatment were assessed. A single oral dose of APAP 3 g/kg (total body weight) was administered to both littermates 24 hr after the last dose of PB or beta-NF. Histologic evidence of hepatocellular necrosis and serum hepatic aminotransferase enzymes 48 hr after APAP administration was utilized to evaluate hepatic damage. Hepatic microsomal total cytochrome P450 concentrations, alkoxyresorufin O-dealkylase activities, and 16 beta-testosterone hydroxylase activities were determined to evaluate the effect of APAP overdose on cytochrome P450 enzyme-substrate activities in the presence and absence of PB treatment. APAP overdose produced lower hepatotoxicity in the obese Zucker rat compared to lean controls. A similar trend was observed in animals treated with PB prior to APAP administration. In contrast, beta-NF treatment produced potentiation of APAP toxicity and/or death of both obese and lean Zucker rats. Generally, APAP overdose produced reduction of hepatic cytochrome P450 enzyme-substrate activities. However, obese Zucker rats retained a higher percentage of their pre-APAP-treated enzyme activities which is consistent with the observation that obese Zucker rats are less affected by the hepatotoxic effects of APAP overdosage.
Details
- Title: Subtitle
- Acetaminophen hepatotoxicity: influence of phenobarbital and beta-naphthoflavone treatment in obese and lean Zucker rats
- Creators
- Somsong Tuntaterdtum - Graduate Center for Toxicology, University of Kentucky, Lexington 40536-0082Inder P ChaudharyMichael CibullLarry W RobertsonRobert A Blouin
- Resource Type
- Journal article
- Publication Details
- Toxicology and applied pharmacology, Vol.123(2), pp.219-225
- Publisher
- United States
- DOI
- 10.1006/taap.1993.1240
- PMID
- 8248929
- ISSN
- 0041-008X
- eISSN
- 1096-0333
- Grant note
- GM 42058 / NIGMS NIH HHS
- Language
- English
- Date published
- 12/1993
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002422102771
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