Autonomous circadian rhythms in the human hepatocyte regulate hepatic drug metabolism and inflammatory responses

Circadian rhythms are crucial for liver homeostasis. In an in vitro liver system, primary human hepatocytes showed 24-hour oscillations, revealing dynamic gene expression related to inflammation, drug metabolism, and energy homeostasis. A treatment protocol was developed to reduce hepatotoxicity from atorvastatin and acetaminophen. Additionally, circadian phases significantly influenced pro-inflammatory cytokine induction in response to infections, highlighting their impact on drug efficacy and toxicity.