Global gene expression profile in the liver and blood of rats administered a toxic dose of acetaminophen

Abstract

The objective of the study was to compare global gene expression profile in the target organ (liver) and a surrogate tissue (blood) in rats administered a toxic dose of the hepatotoxic drug, acetaminophen (AP). Blood and liver were obtained from rats 24‐hours following administration of an acute toxic dose of AP. AP‐induced hepatotoxicity was evidenced from a significant elevation in the serum level of transaminases and the presence of centrilobular necrosis in the liver of the rats. Microarray analysis of global gene expression profile demonstrated significant differential expression of a large number of genes in the liver and blood of the AP administered rats compared with the controls. Genes belonging to several biological processes that are known to play definite role in the hepatotoxicity induced by AP were found differentially expressed both in the liver and blood of the rats. Cellular processes such as inflammatory response, oxidative stress, apoptosis, and energy metabolism were affected in the liver and blood of the AP‐administered rats. The significant similarity noticed in global gene expression profile between liver and blood of the AP administered rats demonstrated that blood gene expression profiling is an appropriate surrogate approach not only to detect target organ toxicity but also to understand the mechanisms underlying the toxicity induced by AP ‐ a model hepatotoxic chemical.