Pharmacologic cholinesterase inhibition in a mouse model of acetaminophen-induced acute liver failure

Acetaminophen is one of the most widely used analgesics. Taken in overdoses, acetaminophen causes acute liver failure (ALF) with widespread hepatocellular necrosis and parenchymal inflammation leading to a systemic inflammatory syndrome. The nervous system, through the vagus nerve, can down-regulate inflammation by decreasing the release of tumor necrosis factor a (TNF-a) by endotoxin-stimulated macrophages. This anti-inflammatory effect is mediated by an interaction between acetylcholine, the principal neurotransmitter of the vagus nerve, and cholinergic nicotinic acetylcholine receptors on macrophages. Here we…