A recent study published in Science Translational Medicine uncovers how liver cells react after acute liver injuries from common painkillers and demonstrates a method to improve liver regeneration in animal models.
Acetaminophen is a drug that is commonly used to relieve pain, reduce fevers, and alleviate symptoms of the common cold. More commonly referred to as its brand names, Tylenol or Panadol, this drug is widely used and prescribed for a range of conditions. Although it is a common painkiller and usually seen as a relatively safe drug, liver injury and acute liver failure can result from consuming it in high doses or mixing it with alcohol.
Impaired liver regeneration from common painkillers
In normal conditions, the liver regenerates after acute liver injury through the replication of liver cells. However, when the cells fail to regenerate, liver injuries may lead to liver failure. A better understanding of the mechanisms behind why livers sometimes do not effectively regenerate will pave the way for new therapies that address acute liver injury, which can occur from taking common painkillers. A group of scientists in the UK explored how liver cells react to acute injuries and published their novel findings in Science Translational Medicine.
In their study, the authors first discovered evidence of liver cells in a state of halted growth, also known as senescence, in a liver sample from an acute liver failure patient. Next, scientists administered the common painkiller, acetaminophen, to mice as a model of acute liver injury and noted that their liver cells also became senescent, which has not been previously described in previous models of acute liver injury. Adding on to these findings, the group performed experiments showing that this phenomenon was spreading among liver cells through the release of an important molecule called TGF-b.
Inhibiting TGF-b signalling improves liver regeneration
To determine if this mechanism could be blocked to improve liver regeneration, the authors of the study tested a drug that inhibits the receptor for TGF-b in mouse models. Again, mice were treated with acetaminophen, which induced acute liver injury, but the drug inhibitor was able to diminish liver senescence and consequently improve liver regeneration and function.
Common painkillers have greatly improved the quality of care for many patients, but they also bring certain drawbacks, such as the risk of liver injury. Since acute liver injury can occur quickly and lead to devastating consequences, new treatments are necessary to improve the quality of care for patients who experience these injuries.
This study described how senescence of liver cells was contributing to impaired liver regeneration after acute liver injury. By uncovering this mechanism, scientists are more able to effectively target the pathways that are involved and develop treatments to combat this issue.
Written by Branson Chen, BHSc
Reference: Bird TG, Müller M, Boulter L, Vincent DF, Ridgway RA, Lopez-Guadamillas E, Lu WY, Jamieson T, Govaere O, Campbell AD, Ferreira-Gonzalez S. TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. Science Translational Medicine. 2018 Aug 15;10(454):eaan1230.