Thursday, April 25, 2024

Circadian rhythms of the liver can influence drugs’ effectiveness

Amazing stuff! Take your pills on time or your liver will not forgive it! 😊

The influence of the circadian rhythms on all kinds of bodily function has been known for decades. Here is more about it!

"Using tiny, engineered livers derived from human patients, ... researchers found that more than 300 liver genes are under circadian control. These circadian variations affect how much of a drug is available and how effectively the body can break it down. ...
The study also revealed that the liver is more susceptible to infections such as malaria at certain points in the circadian cycle, when fewer inflammatory proteins are being produced. ...
It is estimated that about 50 percent of human genes follow a circadian cycle ...
Most of these genes clustered in two groups — about 70 percent of the genes peaked together, while the remaining 30 percent were at their lowest point when the others peaked. These included genes involved in a variety of functions, including drug metabolism, glucose and lipid metabolism, and several immune processes. ..."

From the abstract:
"Critical aspects of physiology and cell function exhibit self-sustained ~24-hour variations termed circadian rhythms. In the liver, circadian rhythms play fundamental roles in maintaining organ homeostasis. Here, we established and characterized an in vitro liver experimental system in which primary human hepatocytes display self-sustained oscillations. By generating gene expression profiles of these hepatocytes over time, we demonstrated that their transcriptional state is dynamic across 24 hours and identified a set of cycling genes with functions related to inflammation, drug metabolism, and energy homeostasis. We designed and tested a treatment protocol to minimize atorvastatin- and acetaminophen-induced hepatotoxicity. Last, we documented circadian-dependent induction of pro-inflammatory cytokines when triggered by LPS, IFN-β, or Plasmodium infection in human hepatocytes. Collectively, our findings emphasize that the phase of the circadian cycle has a robust impact on the efficacy and toxicity of drugs, and we provide a test bed to study the timing and magnitude of inflammatory responses over the course of infection in human liver."

Circadian rhythms can influence drugs’ effectiveness | MIT News | Massachusetts Institute of Technology MIT researchers find circadian variations in liver function play an important role in how drugs are broken down in the body.


Fig. 1. Primary human hepatocytes display a circadian rhythm in culture.


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