Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury.
Objectives: The efficacy of long-term opioid therapy (LTOT) in treating patients with chronic non-cancer pain (CnCP) is questionable, and the potential risks of adverse effects are well established. The aims were as follows: (1) compare characteristics in patients exposed to LTOT vs non-exposed. (2) Regarding opioid-exposed patients, describe characteristics of patients with risk factors for opioid use disorder or overdose in relation to opioid dosage.
Acute liver failure (ALF) is defined as the loss of hepatic function in conjunction with hepatic encephalopathy and coagulopathy. There is histological evidence of profound hepatocyte damage. If it is not aggressively managed, ALF can be fatal within a few days.
Acute liver failure (ALF) is a rare and dynamic syndrome occurring as a sequela of severe acute liver injury (ALI). Its mortality ranges from 50% to 75% based on the aetiology, patients age and severity of encephalopathy at admission. With improvement in intensive care techniques, transplant-free survival in ALF has improved over time.
Paracetamol has antipyretic and analgesic properties and it is widely used for fever and pain. However, paracetamol is partially metabolized to N-acetyl-p-benzoquinoneimine, which in overdose leads to liver necrosis, urging for safer paracetamol analogues. As the latter, new para-aminophenol derivatives containing fragments of acetic acid, saturated fatty acids and monoethanolamine were synthesized.
Background: Acetaminophen (APAP)-induced acute liver injury (AILI) is the most prevalent cause of acute liver failure and mitochondrial dysfunction plays a dominant role in the pathogenesis of AILI. Mitochondrial transcription factor A (TFAM) is an important marker for maintaining mitochondrial functional homeostasis, but its functions in AILI are unclear. This study aimed to investigate the function of TFAM and its regulatory molecular mechanism in the progression of AILI.
