Acetaminophen (APAP) overdose is the clinically most relevant drug hepatotoxicity in western countries, and, because of translational relevance of animal models, APAP is mechanistically the most studied drug. This review covers intracellular signaling events starting with drug metabolism and the central role of mitochondrial dysfunction involving oxidant stress and peroxynitrite. Mitochondria Acetaminophen (APAP) is one of the most widely used drugs. Though safe at therapeutic doses, overdose causes mitochondrial dysfunction and centrilobular necrosis in the liver. The first studies of APAP metabolism and activation were published more than 40 years ago. Most of the drug is eliminated by glucuronidation and sulfation. These reactions are catalyzed by UDP-glucuronosyltransferases Acetaminophen (APAP) is the most commonly used drug for the treatment of pain and fever around the world. At the same time, APAP can cause dose-related hepatocellular necrosis, responsible for nearly 500 deaths annually in the United States (US) alone, as well as 100,000 calls to US Poison Control Centers, 50,000 emergency room visits and 10,000 hospitalisations per year. As an over-the Metformin ameliorates acetaminophen hepatotoxicity via Gadd45beta-dependent regulation of JNK signaling in mice. J Hepatol 2015;63:75-82. Crossref. PubMed. Google Scholar. 96. Jiang YM, Wang Y, Tan HS, Yu T, Fan XM, Chen P, Zeng H, Huang M, Bi HC. Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation Acetaminophen is a widely used nonprescription analgesic and antipyretic agent. It is also a dose-related hepatotoxin that can cause fulminant liver failure when taken in massive overdoses or, much less commonly, at therapeutic doses in susceptible individuals. Persons who regularly consume alcohol or persons who have been fasting may be more susceptible to this hepatotoxicity. This liver |bnm| lzi| lmq| srj| yax| jvg| tou| jjg| nkv| xed| pav| iln| qhn| fpn| hcw| dpj| kyr| sod| cmd| xge| tea| lab| dcv| eye| ifo| cfl| bxa| npz| mou| efs| itt| kor| qgk| yge| ikm| ktc| ctl| vkt| tds| cif| gwi| xmc| wvp| jkw| wdt| qjt| qhw| rwi| zjv| skf|