DIFFERENTIAL EFFECTS OF ACETAMINOPHEN AND AFLATOXIN B1 ON EXPRESSION OF&

Glutathione S-transferase (GST) is a superfamily enzyme which plays a major role in detoxification of xenobiotic compounds by catalyzing the conjugation of xenobiotic to cellular glutathione (GSH). GST-P is an important class of GSTs which is expressed during the early stage of life and during developmental stages. Its activity is relatively high during embryogenesis and immediately after birth and diminished in normal adult rat liver. To investigate the effects of hepatotoxic agents such as acetaminophen (APAP) and aflatoxin B1 (AFB1) on liver GST-P in rats during postnatal age, suckling rats age (14±2 days old) were divided into groups (n=5) and treated with both APAP (250 or 450 mg/kg B.W) and AFB1 (3 mg/kg B.W). Livers were removed at different time intervals (2, 6, 12, 18 and 24 h) and processed for GST and GST-P activity at protein and mRNA levels (RT-PCR). Administration of a single high dose of AFB1 (3 mg/kg BW) and APAP (450 mg/kg BW) to weanling rats caused a significant (P< 0.05) induction in total GST activity in developing rats. Based on the Western blotting technique and GST-P specific mRNA amplification by RT-PCR, the GST-pi protein level and its expression were not affected by APAP or AFB1. Despite the inducible effects of AFB1 and APAP on liver total GST activity, GST-P remained unaffected in response to the drugs at protein and mRNA levels.