Elucidating mechanism of drug induced toxicity

In fasted individuals with low hepatic glycogen content especially, hypoxia, mitochondrial inhibition and damage to mitochondrial DNA lead to hepatocellular necrosis.The liver synthesizes, concentrates, and secretes bile acids and excretes other toxicants, such as bilirubin.

Portal blood brings drugs and xenobiotics absorbed by the gut directly to the liver in concentrated form.The importance of vascular (Kupffer cells, neutrophils) and intracellular generation of reactive oxygen by mitochondria and xenobiotic-inducible enzymes (e.g., CYP 4502E1) will be discussed.Bile formation is an essential function of the liver, and failure of bile formation is a pathophysiologic process termed cholestasis.Drugs continue to be pulled from the market with disturbing regularity because of late discovery of hepatotoxicity.Such unexpected toxicities appear to be the consequence of the unique vascular, secretory, synthetic, and metabolic features of the liver.