We are analyzing https://link.springer.com/article/10.1007/s00418-007-0289-3.

Title:
Chromatin breakdown by deoxyribonuclease1 promotes acetaminophen-induced liver necrosis: an ultrastructural and histochemical study on male CD-1 mice | Histochemistry and Cell Biology
Description:
We analyzed in male wild-type (WT) and Dnase1 knockout (KO) CD-1 mice after acetaminophen (APAP)-intoxication the hepatolobular distribution of APAP-adducts in relation to DNA-damage by terminal deoxyribonucleotidyl-transferase dUTP nick end-labeling (TUNEL), the ultrastructural alterations of hepatocellular morphology and the intracellular localization of Dnase1. Treatment of WT-mice with 600 mg/kg APAP led to extensive pericentral necrosis. Electron microscopy (EM) demonstrated vesiculation of the rough endoplasmatic reticulum and swelling of mitochondria. Pericentral WT-hepatocyte nuclei exhibited pyknosis, karyorrhexis and karyolysis. In contrast, livers from treated KO-mice exhibited almost normal light microscopical structure and EM revealed only mild signs of hepatocellular damage. In WT-mice several layers of pericentral hepatocytes displayed APAP-adduct formation and subsequent DNA-damage, whereas in KO-animals only few cells were affected. Serum aminotransferases rose similarly in both mouse strains up to 12 h, thereafter increased only in WT-mice. Immunogold-EM revealed the translocation of Dnase1 from the rER into the nuclei of treated WT-mice. In KO-mice, APAP-adduct formation was retarded and less extensive suggesting that detoxification of APAP must have been more effective in KO-mice possibly due to the lack of energy depletion otherwise caused by Dnase1-induced DNA-damage in WT-mice.
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article, google, scholar, cas, pubmed, acetaminopheninduced, cell, necrosis, liver, mice, acetaminophen, toxicol, death, dnase, mannherz, napirei, hepatotoxicity, apoptosis, pharmacol, deoxyribonuclease, mouse, role, dna, jaeschke, sci, cells, hepatic, injury, ray, privacy, cookies, content, ultrastructural, jacob, wtmice, access, hinson, biol, data, publish, search, study, male, knockout, hepatocellular, microscopy, human, lupus, nature, bajt,

Topics {✒️}

n-acetyl-p-benzoquinone-imine parp-1 month download article/chapter dnase1-induced dna-damage acetaminophen-induced liver injury acetaminophen-induced hepatic necrosis acute acetaminophen-induced hepatotoxicity 600 mg/kg apap led mitochondrial permeability transition cell-cell tight junctions treated ko-mice exhibited cultured mouse hepatocytes ko-mice possibly due acetaminophen-induced hepatocellular apoptosis acute liver necrosis subsequent dna-damage full article pdf related subjects drug-protein adducts male wild-type acetaminophen-induced injury bcl-xl sensitive apoptosis apap-adduct formation acetaminophen-induced hepatotoxicity extensive pericentral necrosis privacy choices/manage cookies mouse liver cells toxicant-induced injury large genomic dna dnase1 knockout mouse human hepatic cells acetaminophen-induced programmed acetaminophen-induced cytotoxicity ray sd acetaminophen protein adduct cell biology aims rough endoplasmatic reticulum male cd-1 mice apoptosis-inducing factor human hepatoma cells human small intestine cell fine structure dna-damage treated wt-mice acetaminophen modulates expression article jacob article histochemistry intracellular adenosine triphosphate unprogrammed cell death systemic lupus erythematosus european economic area

Questions {❓}

Gujral JS, Knight TR, Farhood A, Bajt ML, Jaeschke H (2002) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis?

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