Restraint of Acetaminophen - Induced Liver Injury with Butylated Hydroxyanisole and Butylated Hydroxytoluene, and Its Effects on Hepatic Heat Shock Protein 25 and 70i

We examined the effects of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on acetaminophen - induced hepatotoxicity using two different administration methods; i.e, feeding rats with BAH- and BHT- added diets, and by direct oral administration. In the former case, BHA and BHT (0.5% each) were separately added to experimental diets which were given to rats for 7 days, and then after a 16 h - fast, APAP (500mg / kg) was intraperitneally given. The oral administration of BHA or BHT (125 mg / kg body weight) was carried out 2 h before the APAP treatment. The elevation of the plasma AST and ALT activities as an index of liver injury was significantly suppressed in the BHA- and BHT- fed groups at 24 h after the APAP treatment and significantly lower levels in the BHA oral pretreatment group were seen when compared with those in the APAP group. On the other hand, the BHT oral pretreatment group showed rather high AST and ALT activities. The restraint function was clarified when BHA and BHT were fed, and also when BHA was orally administered, although a similar function was not observed in case of the oral administration of BHT. The inductions of Hsp25 and Hsp70i by APAP were not depressed by the BHA administration, but were suppressed by the BHT except in the case of Hsp70i in the group orally given BHT. These results suggest that BHT blocks NAPQI to covalently bind to the cellular macromolecules, although BHA does not.