Toxicology
Assessment of Hepatotoxicity Using the Non-Invasive M30 Apoptosense® ELISA
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 1 000 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 increased levels of caspase-cleaved K18 in the circulation (see Application field Hepatology). Not unexpectedly, acetaminophen-induced liver toxicity leads to increased tissue reactivity to the M30 monoclonal antibody (Kass et al., 2003).
Caspase-cleaved and uncleaved forms of K18 were recently demonstrated in the serum of acetaminophen-treated mice (Antoine et al., 2009). Serum K18 showed strong correlation with the time course of hepatotoxicity and was more sensitive than alanine aminotransferase activity. These findings show that circulating forms of K18 are useful biomarkers for assessment of liver toxicity.
» Brochure: M30 Apoptosense ELISA and M65 EpiDeath ELISA - Serum Biomarkers for Toxic Liver Injury
Literature
| » | Greystoke A, O'Connor JP, Linton K, Taylor MB, Cummings J, Ward T, Maders F, Hughes A, Ranson M, Illidge TM, Radford J, Dive C Assessment of circulating biomarkers for potential pharmacodynamic utility in patients with lymphoma Br J Cancer. 2011, 104:719-25 |
