Acetaminophen (AAP) overdose and the resulting hepatotoxicity is an important clinical
problem. In addition, AAP is widely used as a prototype hepatotoxin to study mechanisms of …

Several important drug classes show pre-clinical hepatotoxicity or, in some cases
hepatotoxicity in man in Phase III/IV not predicted by pre-clinical studies. This hepatotoxicity …

Intracellular sources of peroxynitrite formation and potential targets for this powerful oxidant
and nitrating agent have not been identified after acetaminophen (AAP) overdose …

BACKGROUND/AIMS: Although mitochondria have been demonstrated as primary targets in
acetaminophen hepatotoxicity, the mechanism for mitochondria-mediated toxicity has not …

Freshly isolated mouse hepatocytes were used to determine the role of mitochondrial
permeability transition (MPT) in acetaminophen (APAP) toxicity. Incubation of APAP (1 mM) …

The history of the development of the analgestic drug acetaminophen is reviewed with an
emphasis on the characteristics of its overdose toxicity. The P450-catalyzed oxidation of …

We hypothesized that superoxide from Kupffer cells (KC) contributes to
hepatocarcinogenesis. p47phox−/− mice, deficient in phagocyte NADPH oxidase and …

Mitochondrial aldehyde dehydrogenase (ALDH2) is responsible for the metabolism of
acetaldehyde and other toxic lipid aldehydes. Despite many reports about the inhibition of …

The pregnane X receptor (PXR) is a transcriptional regulator of xenobiotic metabolizing
enzymes, including cytochrome P450 3A (CYP3A), and transporters. Pretreatment of mice …

DNA fragmentation in hepatocytes occurs early after acetaminophen (AAP) overdose in
mice. DNA strandbreaks can induce excessive activation of poly (ADP-ribose) polymerases …