Liver toxicity is a major problem during development of new drugs. The liver has a close relationship with the gastrointestinal tract and will metabolize orally adminstered drugs. Almost 1000 drugs have been implicated as being hepatotoxic and liver toxicity is a common reason for drug attrition.
As described elsewhere on this website, liver diseases characterized by hepatocyte apoptosis lead to increase levels of caspase-cleaved CK18 in the circulation (see Application field Hepatology). Not unexpecedly, acetaminophen-induced liver toxicity leads to increased tissue reactivity to the M30 monoclonal antibody (Kass et al., 2003).
Caspase-cleaved and uncleaved forms of CK18 were recently demonstrated in the serum of acetaminophen-treated mice (Antoine et al., 2009). Serum CK18 showed strong correlation the time course of hepatotoxicity and was more sensitive than alanine aminotransferase activity. These findings show that circulating forms of CK18 are useful biomarkers for assessment of liver toxicity.
