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2012 | 15 | 4 | 24-30
Article title

The influence of single application of paracetamol and/or N-acetylcysteine on rats in subchronic exposition to trichloroethylene vapours. III. Effect on some isoforms of cytochrome P450 in liver

Title variants
Wpływ pojedynczej dawki paracetamolu i/lub N-acetylocysteiny na szczury przewlekle eksponowane na trichloroetylen. III. Wpływ na wybrane izoformy cytochromu P450 w wątrobie
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Background: 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. Materials
and method: 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 of
CYP1A2. 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
Wstęp: W przypadku przedawkowania paracetamolu,
zdolność wątroby do detoksykacji zostaje wysycona i następuje
akumulacja toksycznego metabolitu, jaki jest NAPQI.
Główne izoformy CYP, uważane za odpowiedzialne za bioaktywację
APAP-u i sprzyjające w ten sposób zatruciom
wątrobowym, to CYP2E1, CYP1A2 oraz CYP3A4 a u zwierząt
dodatkowo izoformy 2B1/2. Celem pracy było zbadanie
wpływu paracetamolu i/lub trichloroetylenu na skład
wątrobowych izoform cytochromu P450. Materiał i metody:
Badania wykonano na szczurach, które traktowano
trichloroetylenem, paracetamolem i/lub N-acetylocysteiną.
We frakcji mikrosomalnej wątroby oznaczano zawartość
trzech izoform cytochromu P450, tj., CYP2E1, CYP2B1/2
oraz CYP1A2. Wyniki: Paracetamol lekko stymulował
CYP2E1 obniżając równocześnie poziom CYP1A2. Trichloroetylen
stymulował CYP2B1/2. N-acetylocysteina miała
stymulujący wpływ na wszystkie badane izoformy P450.
N-acetylocysteina podawana łącznie z badanymi ksenobiotykami
prowadziła do wyraźnych wzrostów CYP. Wnioski:
N-acetylocysteina wykazywała ochronny wpływ na
poziomy badanych izoform cytochromu P450, szczególnie,
jeśli została podana zaraz po zaprzestaniu ekspozycji na
  • Department of Histology, Medical University of Silesia, Katowice
  • Department of Proteomics, Medical University of Silesia, Sosnowiec
  • Department of Toxicology, Medical University, Poznań
  • Department of Toxicology, Medical University, Poznań
  • Department of Toxicology, Medical University, Poznań
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