Drug-induced liver injury (DILI) is a prevalent drug side effect that ranks second behind cardiotoxicity in drug target organ toxicity. This injury is often a key factor in forced interruptions of drug development programs or withdrawal of drugs from the market. To delve deeper into DILI and its associated pharmacotoxicology, researchers rely on the Hepatotoxic Drug Database, a powerful resource. The database contains 1,395 chemicals known to cause liver damage, covering a wide range of categories from antitumor drugs to antibiotics, antipsychotics to cardiovascular drugs. The database provides a detailed record of each drug's chemical structure, CAS registration number, type of pharmacological action, as well as their performance in clinical applications and potential adverse effects. In addition, it meticulously describes the mechanisms by which each drug induces hepatic injury, which usually involve complex pathological processes including, but not limited to, direct disruption of liver structure and function (e.g., mitochondrial dysfunction); production of metabolites that affect hepatocyte structure and function; formation of active drug metabolites that can bind to hepatic proteins, which in turn generates new drug-protein complexes that are antigenic, and these new complexes are recognized as foreign by the immune system in the host body (semi-antigenic hypothesis) and trigger a systemic hypersensitivity reaction to liver damage (i.e., drug allergy). By systematically organizing and continuously updating this information, the database will be of inestimable value in unraveling the pathogenesis of DILI, discovering biomarkers for predicting its developmental trends, and ultimately realizing effective prevention and management of DILI.
