Please read Dr. Aleksunes’ article in the Journal of Hazardous Materials titled, “Mechanism-driven modeling of chemical hepatotoxicity using structural alerts and an in vitro screening assay.“
The liver plays a critical role in detoxification and metabolism, which makes it highly vulnerable to injury by exogenous compounds, such as environmental chemicals, commercial products, and drugs. Hepatotoxicity represents the acute and chronic liver injuries that are caused by chemicals. Hepatotoxicity is also the leading cause of drug failure in clinical trials and withdrawal from the market. Between 1975 and 2007, 32% of drug withdrawals were attributed to hepatotoxicity, causing significant losses in pharmaceutical companies. Testing for chemical hepatotoxicity is time-consuming and expensive, usually necessitating the administration of chemical candidates to large numbers of animals in safety studies. Often, animal models fail to detect the idiosyncratic hepatotoxicity subsequently observed in humans during clinical testing and post marketing surveillance. For example, a retrospective analysis revealed that animal testing missed 45% of hepatotoxicity cases during clinical trials. As alternatives to animal testing, in vitro approaches, particularly those developed by high-throughput screening (HTS) techniques, have been applied to evaluate drug toxicity. However, individual in vitro assays cannot fully replace in vivo testing as they address relatively simple toxicity mechanisms. To read the full article.
Mechanism-driven modeling of chemical hepatotoxicity using structural alerts and an in vitro screening assay. Jia X, Wen X, Russo DP, Aleksunes LM, Zhu H .J Hazard Mater. 2022 Aug 15;436:129193. PMID: 35739723 PMCID: PMC9262097 DOI: 1016/j.jhazmat.2022.129193 Epub 2022 May 20.