Acetaminophen-Induced Hepatotoxicity: Still an Impor- tant Issue

Abbreviations: ALT, alanine aminotransferase; APAP, acetaminophen; CoQ10, oxidized coenzyme Q10; CoQ9H2, reduced coenzyme Q9; CoQ10H2, reduced coenzyme Q10; CYP, cytochrome P450; GSH, reduced glutathione; GSSG, oxidized glutathione; HSP, heat shock protein; MEOS, microsomal ethanol oxidizing system; NAC, N-acetylcysteine; NAPQI, N-acetyl-p-benzoquinoneimine; ROS, reactive oxygen species; SAMC, S-allylmercaptocysteine; TBARS, thiobarbituric acid-reactive substance; α-Toc, α-tocopherol Acetaminophen (N-acetyl-p-aminophenol, APAP), also referred to as paracetamol, is widely used as an analgesic and antipyretic drug throughout the world. In the United Kingdom, about 3.2 × 10 tablets of APAP are consumed every year, which is equivalent to an average of 55 tablets/person (Jones, 1998). As an over-the-counter drug, it can be readily obtained without prescription. Although APAP is generally harmless at therapeutic doses, overdose causes hepatotoxicity (Davidson and Eastham, 1966; Mitchell, 1988). In addition, susceptibility to APAP-induced hepatotoxicity is modified by various factors such as alcohol abuse, fasting and concomitant drug use. In Japan, APAP has usually been consumed as combination tablets or granules and rarely used alone except as a suppository. However, since recent reports that the use of salicylic acid in combination cold remedies is associated with Acetaminophen-Induced Hepatotoxicity: Still an Important Issue