DIFFERENTIAL EFFECTS OF ACETAMINOPHEN AND AFLATOXIN B1 ON EXPRESSION OF LIVER CLASS-P GLUTATHIONE S-TRANSFERASE IN GROWING RATS

Abstract

Glutathione S-transferase (GST) is a superfamily enzyme which plays a major role indetoxification 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 duringdevelopmental stages. Its activity is relatively high during embryogenesis and immediately after birth anddiminished 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 daysold) were divided into groups (n=5) and treated with both APAP (250 or 450 mg/kg B.W) and AFB1 (3mg/kg B.W). Livers were removed at different time intervals (2, 6, 12, 18 and 24 h) and processed for GSTand GST-P activity at protein and mRNA levels (RT-PCR). Administration of a single high dose of AFB1 (3mg/kg BW) and APAP (450 mg/kg BW) to weanling rats caused a significant (P< 0.05) induction in totalGST activity in developing rats. Based on the Western blotting technique and GST-P specific mRNAamplification 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 inresponse to the drugs at protein and mRNA levels.