Protective Effect of Butylated Hydroxyanisole and Butylated Hydroxytoluene against Acetaminophen-Induced Hepatotoxicity in Rats

Abstract

We assessed the protective effect of the dietary antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) against acetaminophen (APAP)-induced hepatotoxicity. After giving diets containing BHA (0.5%), BHT (0.5%) to male Wistar rats for 7 days, they were fasted for 16 h and then intraperitoneally injected with APAP (0.5g/kg). The severity of the hepatic injury was inferred from the plasma alanine aminotransferase and aspartate aminotransaferase levels 24 h later. The results indicated that BHA and BHT significantly protected the rats against APAP hepatotoxicity. Upon investigating the mechanism of the protective action of BHA and BHT, the hepatic glutathione (GSH) levels decreased to the same degree in the APAP, BHA + APAP, and BHT + APAP groups 2 h after the injection of APAP, while the GSH levels started to recover in all groups at 6 h, but increasing faster in the BHA + APAP and BHT + APAP groups than in the APAP group. As compared with the control group, the hepatic cytochrome P450 (CYP) 2E1 levels tended to be about 20% higher in the BHA + APAP group from 2 to 24 h, and about 30% higher in the BHT + APAP group only at 24 h. These results suggest that the protection against APAP-induced hepatotoxicity provided by BHA and BHT is partly due to rapid recovery of the hepatic glutathione levels but does not involve changes in the CYP2E1 levels.