p53 has a role during acetaminophen overdose mediated liver injury

Acetaminophen (APAP) is a pain medicine. This drug is used to treat a variety of conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, fevers, and patent ductus arteriosus. APAP overdose is a common poisoning worldwide because people often think that this drug is very safe. In fact, acute overdoses of APAP can trigger fatal liver damage. In the US and the UK, APAP toxicity is the leading cause of acute liver failure. However, treatment strategies for APAP overdose are seriously limited. Additionally, not all patients are suitable for liver transplantation.

Now a new study has illustrated that the p53 protein impacts the progression of liver damage as well as tissue repair after an acetaminophen (APAP) overdose. The was led by Udayan Apte at the University of Kansas Medical Center. Apte noted that it is imperative to develop novel treatments.

The researchers previously found that liver regeneration in response to APAP overdose a critical determinant of patient survival. The primary aim of the new study is to determine the mechanisms that impact liver injury progression and liver regeneration.

Liver regeneration involves replication of the liver cells. The p53 protein is known to regulate cell cycle and apoptosis, but its function in liver regeneration after APAP overdose induced liver injury remains unclear. In this work, Apte's team investigated two group of mice: the normal mice and the mice that lacked p53. After treated with APAP, the p53-deficient mice exhibited more significant liver damage but more rapid liver regeneration compared to the normal mice. Collectively, the data illustrate that p53 is involved in inhibiting liver injury progression and liver regeneration following APAP overdose induced liver injury.

Further investigation revealed that the p53-deficient mice had disrupted metabolic homeostasis, induced pro-inflammatory and proliferative signaling. Western blot analysis of EGFR, ERK and AKT demonstrated that these animals had sustained growth factor signaling.

These findings may lead to new drugs that target p53 for the prevention and treatment for APAP overdose mediated liver injury. The study is present at the ASIP annual meeting during the Experimental Biology 2017 meeting, to be held April 22-26 in Chicago. (Cusabio offers p53, EGFR, ERK, AKT, and other proteins and antibodies such as Recombinant Ptpra for researchers doing related experiments.)