RESEARCH PAPER
Wpływ pojedynczej dawki paracetamolu i/lub N-acetylocysteiny
na szczury przewlekle eksponowane na trichloroetylen.
III. Wpływ na wybrane izoformy cytochromu P450 w wątrobie
1
Department of Histology, Medical University of Silesia, Katowice.
Head of Department: R. Wiaderkiewicz MD, PhD, associated professor
2
Department of Proteomics, Medical University of Silesia, Sosnowiec. Head of Department: Prof. A. Plewka MD PhD
3
Department of Toxicology, Medical University, Poznań. Head of Department: Prof. J. Jodynis-Liebert PhD
Corresponding author
Andrzej Plewka
Department of Proteomics, Medical University of Silesia, ul. Ostrogórska 30 41-200 Sosnowiec tel./fax +48 32 364-14-40 e-mail: aplewka@sum.edu.pl
Department of Proteomics, Medical University of Silesia, ul. Ostrogórska 30 41-200 Sosnowiec tel./fax +48 32 364-14-40 e-mail: aplewka@sum.edu.pl
Med Srod. 2012;15(4):24-30
KEYWORDS
ABSTRACT
Introduction:
In case of overdose of paracetamol the,ability of hepatic biotransformation is saturated and accumulation,of toxic metabolite – NAPQI takes place. Main,CYP isoforms considered to be responsible for bioactivation,of APAP and promoting the same liver intoxication are,CYP2E1, CYP1A2, CYP3A4 and in animals 2B1/2 isoforms additionally. Purpose of this work was examination of paracetamol influence and/or trichloroethylene on the composition of hepatic cytochrome P450 isoforms.
Material and Methods:
Tests were carried out on rats which were treated with trichloroethylene, paracetamol and/or N-acetylcysteine. In the microsomal fraction content of three isoforms of cytochrome P450 i.e. CYP2E1, CYP2B1/2 and CYP1A2 were determined.
Results:
Paracetamol slightly stimulated CYP2B1/2 lowering simultaneously level ofCYP1A2. Trichloroethylene stimulated CYP2B1/2. N-acetylcysteine stimulated all tested P450 isoforms. N-acetylcysteine given together with examinated xenobiotics induced studied P450 isoforms.
Conclusions:
N-acetylcysteine demonstrated a protective effect on studied CYP isoforms especially when was given upon termination of xenobiotics exposure.
In case of overdose of paracetamol the,ability of hepatic biotransformation is saturated and accumulation,of toxic metabolite – NAPQI takes place. Main,CYP isoforms considered to be responsible for bioactivation,of APAP and promoting the same liver intoxication are,CYP2E1, CYP1A2, CYP3A4 and in animals 2B1/2 isoforms additionally. Purpose of this work was examination of paracetamol influence and/or trichloroethylene on the composition of hepatic cytochrome P450 isoforms.
Material and Methods:
Tests were carried out on rats which were treated with trichloroethylene, paracetamol and/or N-acetylcysteine. In the microsomal fraction content of three isoforms of cytochrome P450 i.e. CYP2E1, CYP2B1/2 and CYP1A2 were determined.
Results:
Paracetamol slightly stimulated CYP2B1/2 lowering simultaneously level ofCYP1A2. Trichloroethylene stimulated CYP2B1/2. N-acetylcysteine stimulated all tested P450 isoforms. N-acetylcysteine given together with examinated xenobiotics induced studied P450 isoforms.
Conclusions:
N-acetylcysteine demonstrated a protective effect on studied CYP isoforms especially when was given upon termination of xenobiotics exposure.
FUNDING
This work was supported by Ministry of Health grants
KBN - 4 P05D 021 15
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