FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1992105600> ?p ?o ?g. }

• W1992105600 endingPage "336" @default.
• W1992105600 startingPage "326" @default.
• W1992105600 abstract "Acetaminophen (APAP) overdose is a frequent cause of drug-induced liver injury and the most frequent cause of acute liver failure in the Western world. Previous studies with mouse models have revealed that impairment of mitochondrial respiration is an early event in the pathogenesis, but the exact mechanisms have remained unclear, and therapeutic approaches to specifically target mitochondria have been insufficiently explored. Here, we found that the reactive oxidative metabolite of APAP, N-acetyl-p-benzoquinoneimine (NAPQI), caused the selective inhibition of mitochondrial complex II activity by >90% in both mouse hepatic mitochondria and yeast-derived complexes reconstituted into nanoscale model membranes, as well as the decrease of succinate-driven adenosine triphosphate (ATP) biosynthesis rates. Based on these findings, we hypothesized that methylene blue (MB), a mitochondria-permeant redox-active compound that can act as an alternative electron carrier, protects against APAP-induced hepatocyte injury. We found that MB (<3 µM) readily accepted electrons from NAPQI-altered, succinate-energized complex II and transferred them to cytochrome c, restoring ATP biosynthesis rates. In cultured mouse hepatocytes, MB prevented the mitochondrial permeability transition and loss of intracellular ATP without interfering with APAP bioactivation. In male C57BL/6J mice treated with APAP (450 mg/kg, intraperitoneally [IP]), MB (10 mg/kg, IP, administered 90 minutes post-APAP) protected against hepatotoxicity, whereas mice treated with APAP alone developed massive centrilobular necrosis and increased serum alanine aminotransferase activity. APAP treatment inhibited complex II activity ex vivo, but did not alter the protein expression levels of subunits SdhA or SdhC after 4 hours. Conclusion: MB can effectively protect mice against APAP-induced liver injury by bypassing the NAPQI-altered mitochondrial complex II, thus alleviating the cellular energy crisis. Because MB is a clinically used drug, its potential application after APAP overdose in patients should be further explored. (Hepatology 2015;61:326–336)" @default.
• W1992105600 created "2016-06-24" @default.
• W1992105600 creator A5033699246 @default.
• W1992105600 creator A5055599271 @default.
• W1992105600 creator A5074067636 @default.
• W1992105600 creator A5077512138 @default.
• W1992105600 creator A5079050868 @default.
• W1992105600 date "2014-12-15" @default.
• W1992105600 modified "2023-09-30" @default.
• W1992105600 title "Targeting mitochondria with methylene blue protects mice against acetaminophen‐induced liver injury" @default.
• W1992105600 cites W1479794699 @default.
• W1992105600 cites W1482264334 @default.
• W1992105600 cites W1516582678 @default.
• W1992105600 cites W1541799695 @default.
• W1992105600 cites W185276893 @default.
• W1992105600 cites W1863232447 @default.
• W1992105600 cites W1986862254 @default.
• W1992105600 cites W1990355599 @default.
• W1992105600 cites W1991418253 @default.
• W1992105600 cites W1992543987 @default.
• W1992105600 cites W1997037955 @default.
• W1992105600 cites W1997878364 @default.
• W1992105600 cites W2009705589 @default.
• W1992105600 cites W2013832046 @default.
• W1992105600 cites W2022827665 @default.
• W1992105600 cites W2026239829 @default.
• W1992105600 cites W2026599956 @default.
• W1992105600 cites W2027397755 @default.
• W1992105600 cites W2039632673 @default.
• W1992105600 cites W2056309362 @default.
• W1992105600 cites W2058056447 @default.
• W1992105600 cites W2059775504 @default.
• W1992105600 cites W2061945989 @default.
• W1992105600 cites W2062684221 @default.
• W1992105600 cites W2065715946 @default.
• W1992105600 cites W2071276901 @default.
• W1992105600 cites W2072445126 @default.
• W1992105600 cites W2073224154 @default.
• W1992105600 cites W2074545478 @default.
• W1992105600 cites W2076372222 @default.
• W1992105600 cites W2078116832 @default.
• W1992105600 cites W2078788856 @default.
• W1992105600 cites W2079118329 @default.
• W1992105600 cites W2079762064 @default.
• W1992105600 cites W2080577934 @default.
• W1992105600 cites W2081086157 @default.
• W1992105600 cites W2084621494 @default.
• W1992105600 cites W2084675528 @default.
• W1992105600 cites W2088602491 @default.
• W1992105600 cites W2110572140 @default.
• W1992105600 cites W2112882492 @default.
• W1992105600 cites W2129354263 @default.
• W1992105600 cites W2133899059 @default.
• W1992105600 cites W2163790438 @default.
• W1992105600 cites W250102117 @default.
• W1992105600 cites W4250743572 @default.
• W1992105600 doi "https://doi.org/10.1002/hep.27385" @default.
• W1992105600 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25142022" @default.
• W1992105600 hasPublicationYear "2014" @default.
• W1992105600 type Work @default.
• W1992105600 sameAs 1992105600 @default.
• W1992105600 citedByCount "73" @default.
• W1992105600 countsByYear W19921056002015 @default.
• W1992105600 countsByYear W19921056002016 @default.
• W1992105600 countsByYear W19921056002017 @default.
• W1992105600 countsByYear W19921056002018 @default.
• W1992105600 countsByYear W19921056002019 @default.
• W1992105600 countsByYear W19921056002020 @default.
• W1992105600 countsByYear W19921056002021 @default.
• W1992105600 countsByYear W19921056002022 @default.
• W1992105600 countsByYear W19921056002023 @default.
• W1992105600 crossrefType "journal-article" @default.
• W1992105600 hasAuthorship W1992105600A5033699246 @default.
• W1992105600 hasAuthorship W1992105600A5055599271 @default.
• W1992105600 hasAuthorship W1992105600A5074067636 @default.
• W1992105600 hasAuthorship W1992105600A5077512138 @default.
• W1992105600 hasAuthorship W1992105600A5079050868 @default.
• W1992105600 hasBestOaLocation W19921056001 @default.
• W1992105600 hasConcept C13591479 @default.
• W1992105600 hasConcept C181199279 @default.
• W1992105600 hasConcept C185592680 @default.
• W1992105600 hasConcept C190283241 @default.
• W1992105600 hasConcept C202751555 @default.
• W1992105600 hasConcept C23265538 @default.
• W1992105600 hasConcept C2776200302 @default.
• W1992105600 hasConcept C2776637226 @default.
• W1992105600 hasConcept C2778722691 @default.
• W1992105600 hasConcept C2779564974 @default.
• W1992105600 hasConcept C28859421 @default.
• W1992105600 hasConcept C31573885 @default.
• W1992105600 hasConcept C55493867 @default.
• W1992105600 hasConcept C86803240 @default.
• W1992105600 hasConcept C98274493 @default.
• W1992105600 hasConceptScore W1992105600C13591479 @default.
• W1992105600 hasConceptScore W1992105600C181199279 @default.
• W1992105600 hasConceptScore W1992105600C185592680 @default.
• W1992105600 hasConceptScore W1992105600C190283241 @default.
• W1992105600 hasConceptScore W1992105600C202751555 @default.

• next