Current Research and Scholarly Interests
Acetaminophen – N-acetyl-p-amino-phenol (APAP) , Tylenol™ - is an over the counter drug used for its analgesic, antipyretic and peripheral anti-inflammatory effects. APAP is the most widely studied of all drugs known to have hepatotoxic potentials. Its regioisomer N-acetyl-m-amino-phenol (AMAP) cause no injury to the liver and appears to be relatively safe. APAP overdose has been reported to cause liver injury, necrosis acute liver failure and over 450 deaths yearly in the United State. Implicated in these series of adverse effect is N-acetyl-p-benzoquinone imine (NAPQI) the reactive metabolite formed from a fraction of APAP metabolism by cytochrome p450 enzymes. Conjugation of NAPQI with glutathione (GSH) leads to its biliary excretion. Subsequent GSH depletion and accumulation of NAPQI, results in NAPQI preferential binding to cellular proteins and other macromolecules. NAPQI -protein binding is implicated in APAP toxicity. Consequently, activation of Kupffer cells (KC) and neutrophil recruitment exacerbate these situation. N-acetyl cysteine (NAC) from inception in the 1970’s as a antidote of APAP toxicity, still finds relevance in the management of accidental or suicidal APAP overdose.