Why can the most commonly used antipyretic analgesic cause liver damage?Preliminary declassification of a joint study by the People’s Hospital of Wuhan University

2022-09-10 0 By

(Correspondent Yang Cen) Acetaminophen (APAP) is one of the most commonly used antipyretic and analgesic drugs, but its overuse is the most common drug poisoning, and also the main cause of acute liver failure in the world, and its mechanism remains unknown.Recently, a team of interdisciplinary researchers from two schools of Wuhan University joined hands to solve the mystery.On March 21, Hepatology, a leading international journal of Hepatology,IF=17.425) “Loss of Sam50 in induces cardiolipin-dependent mitochondrial membrane reconstruction resulting in mitochondrial DNA release and liver injury” was published online by Jieqing Song, Professor, School of Life Sciences, Wuhan University, and Qingtao Meng, Professor, Renmin Hospital of Wuhan University, as co-corresponding authorThe hepatocyte induces cardiolipin-dependent mitochondrial membrane remodeling to triggermtDNArelease and liver injury “.The results show that cardiolipin externalization due to loss (or reduction) of SAM50, a mitochondrial outer membrane translocation enzyme, is a signal for the release of mitochondrial DNA (mtDNA) from hepatocytes and induces liver injury.This result provides a new potential target and theoretical basis for the treatment of hepatic toxicity of acetaminophen (APAP), and also provides a new idea for the molecular mechanism and prevention and treatment of multiple organ dysfunction.Meng Qingtao introduced that people are exposed to more than 30,000 kinds of drugs and health care products in daily life, among which more than 1,000 kinds of drugs clearly can cause liver damage.Therefore, drug-induced liver injury has become a serious public health problem that cannot be ignored.Previous studies have found that excessive paracetamol (APAP) can cause oxidative stress and dysfunction of human mitochondria, and eventually lead to liver cell necrosis and liver damage.Although there is increasing evidence for the role of mitochondria in APAP-induced liver injury, the mechanism by which APAP causes DAMP (damage-related molecular pattern) release and subsequent liver injury remains unclear.Professor Xia Zhongyuan (left), Director of the Department of Anesthesiology, Renmin Hospital of Wuhan University, and Professor Meng Qingtao (right), deputy director of the Department of Anesthesiology, Renmin Hospital of Wuhan University, found that SAM50 plays a key role in maintaining the integrity of mitochondrial membrane and the stability of mitochondrial DNA of hepatocytes in this “life science + Medicine” joint study.In mouse models, loss of SAM50 leads to cardiolipin migration (intima to outer membrane) and ultimately to liver damage in mice.In addition, in the model study of liver injury caused by acetaminophen overdose, if the Sam50 protein is significantly upregulated, the release of mtDNA can be reduced, thus alleviating the liver injury caused by acetaminophen overdose.This research was supported by the General program of The National Natural Science Foundation of China and the Key RESEARCH and Development Program of the Ministry of Science and Technology, and it also deepened and extended the preliminary research results of the Department of Anesthesiology, People’s Hospital of Wuhan University.It is reported that the People’s Hospital of Wuhan University attaches great importance to promoting the development of people’s health through scientific and technological innovation.Recent close exchanges and cooperation with related wuhan university college hospital, set up medical professionals fusion research, translational medicine research institute, institute of innovation, planning established molecular medicine research institute, institute of medical research institute of remote sensing information, urged discipline integration, aimed at fusion technology advantage, high-end talent research urgently needs to solve clinical problems.This research achievement is also the first important scientific research achievement of the Department of Anesthesiology, Renmin Hospital of Wuhan University, in response to the “crossover and integration” strategy, which is demand-oriented and application-oriented, in cooperation with the School of Life Sciences, School of Chemistry and School of Physics of Wuhan University.