Assessing the translatability of in vivo cardiotoxicity mechanisms to in vitro models using causal reasoning.

ABSTRACT: Drug-induced cardiac toxicity has been implicated in 31% of drug withdrawals in the USA. The fact that the risk for cardiac-related adverse events goes undetected in preclinical studies for so many drugs underscores the need for better, more predictive in vitro safety screens to be deployed early in the drug discovery process. Unfortunately, many questions remain about the ability to accurately translate findings from simple cellular systems to the mechanisms that drive toxicity in the complex in vivo environment. In this study, we analyzed translatability of cardiotoxic effects for a diverse set of drugs from rodents to two different cell systems (rat heart tissue-derived cells (H9C2) and primary rat cardiomyocytes (RCM)) based on their transcriptional response. To unravel the altered pat

SUBMITTER: Enayetallah AE 

PROVIDER: S-EPMC3846863 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature