Histopathological and Immunological Analysis of the Effects of Butylated Antioxidants on Acetaminophen - Hepatotoxity in Rats

  • BOINDOGURONG Jinhua
    Laboratory of Food and Nutrition, Graduate School of Science and Technology, Chiba University
  • EGASHIRA Yukari
    Laboratory of Food and Nutrition, Graduate School of Science and Technology, Chiba University
  • SANADA Hiroo
    Laboratory of Food and Nutrition, Graduate School of Science and Technology, Chiba University

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Acetaminophen (APAP) is mostly eliminated at a therapeutic dose through glucuronidation and sulfatation, while a small fraction is oxidized by cytochromes P450 (CYP) into N-acetyl-P-benzoquinone-imine (NAPQI). NAPQI, a highly reactive metabolite of APAP is then conjugated with glutathione (GSH) and the product can be excreted into the urine. At an APAP overdose, glucuronidation and the sulfatation pathway are saturated and the production of NAPQI increases, resulting in a rapid depletion of the GSH concentration. Subsequently, NAPQI reacts with cellular macromolecules causing hepatic injury. Based on our previous studies, it was shown that APAP-induced hepatotoxity in rats was protected by butylated hydroxyanisol (BHA) and butylated hydroxytoluene (BHT), but the in protection mechanisms could be somewhat different. In this study, we have confirmed the protective effects of BHA and BHT against APAP-induced liver injury using histopathological and morphological observations of the rat liver. Rats were given BHA or BHT (0.5% each) as the ingredient added to their diets for 7 days, then APAP (500 mg / kg IP) was injected. On the other hand, BHA has almost no effects on the induction of hepatic heat shock proteins, but BHT depressed them in the rats administered APAP during 0-24 h. This means that the differences in the inhibition mechanisms of BHA and BHT are the induction of chaperones or other protein(s) and increasing the hepatic GSH accumulation or decreasing the degenerated protein in the hepatic cells by the putative protein conjugated with NAPQI in APAP-induced liver injury.<br>

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