FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3020943404> ?p ?o ?g. }

• W3020943404 endingPage "2748" @default.
• W3020943404 startingPage "2733" @default.
• W3020943404 abstract "Abstract Many drugs have the potential to cause drug-induced liver injury (DILI); however, underlying mechanisms are diverse. The concept of adverse outcome pathways (AOPs) has become instrumental for risk assessment of drug class effects. We report AOPs specific for immune-mediated and drug hypersensitivity/allergic hepatitis by considering genomic, histo- and clinical pathology data of mice and dogs treated with diclofenac. The findings are relevant for other NSAIDs and drugs undergoing iminoquinone and quinone reactive metabolite formation. We define reactive metabolites catalyzed by CYP monooxygenase and myeloperoxidases of neutrophils and Kupffer cells as well as acyl glucuronides produced by uridine diphosphoglucuronosyl transferase as molecular initiating events (MIE). The reactive metabolites bind to proteins and act as neo-antigen and involve antigen-presenting cells to elicit B- and T-cell responses. Given the diverse immune systems between mice and dogs, six different key events (KEs) at the cellular and up to four KEs at the organ level are defined with mechanistic plausibility for the onset and progression of liver inflammation. With mice, cellular stress response, interferon gamma-, adipocytokine- and chemokine signaling provided a rationale for the AOP of immune-mediated hepatitis. With dogs, an erroneous programming of the innate and adaptive immune response resulted in mast cell activation; their infiltration into liver parenchyma and the shift to M2-polarized Kupffer cells signify allergic hepatitis and the occurrence of granulomas of the liver. Taken together, diclofenac induces divergent immune responses among two important preclinical animal species, and the injury pattern seen among clinical cases confirms the relevance of the developed AOP for immune-mediated hepatitis." @default.
• W3020943404 created "2020-05-13" @default.
• W3020943404 creator A5036671376 @default.
• W3020943404 creator A5068092189 @default.
• W3020943404 creator A5089631740 @default.
• W3020943404 date "2020-05-05" @default.
• W3020943404 modified "2023-10-05" @default.
• W3020943404 title "An adverse outcome pathway for immune-mediated and allergic hepatitis: a case study with the NSAID diclofenac" @default.
• W3020943404 cites W1528348540 @default.
• W3020943404 cites W1974541930 @default.
• W3020943404 cites W1976620258 @default.
• W3020943404 cites W1979278210 @default.
• W3020943404 cites W1979456235 @default.
• W3020943404 cites W1982058771 @default.
• W3020943404 cites W1989125414 @default.
• W3020943404 cites W1989300686 @default.
• W3020943404 cites W1989530674 @default.
• W3020943404 cites W1990506447 @default.
• W3020943404 cites W1991588322 @default.
• W3020943404 cites W1998189366 @default.
• W3020943404 cites W2000089305 @default.
• W3020943404 cites W2003181581 @default.
• W3020943404 cites W2003520527 @default.
• W3020943404 cites W2003689725 @default.
• W3020943404 cites W2006563647 @default.
• W3020943404 cites W2006830260 @default.
• W3020943404 cites W2008820962 @default.
• W3020943404 cites W2010965956 @default.
• W3020943404 cites W2015942708 @default.
• W3020943404 cites W2017946433 @default.
• W3020943404 cites W2019148564 @default.
• W3020943404 cites W2020053961 @default.
• W3020943404 cites W2023485739 @default.
• W3020943404 cites W2025259786 @default.
• W3020943404 cites W2026488328 @default.
• W3020943404 cites W2026880056 @default.
• W3020943404 cites W2028132386 @default.
• W3020943404 cites W2029415268 @default.
• W3020943404 cites W2033260525 @default.
• W3020943404 cites W2034179129 @default.
• W3020943404 cites W2035867345 @default.
• W3020943404 cites W2037698110 @default.
• W3020943404 cites W2038304359 @default.
• W3020943404 cites W2039154639 @default.
• W3020943404 cites W2046387493 @default.
• W3020943404 cites W2049151398 @default.
• W3020943404 cites W2054657715 @default.
• W3020943404 cites W2058139653 @default.
• W3020943404 cites W2060663196 @default.
• W3020943404 cites W2068853602 @default.
• W3020943404 cites W2070535546 @default.
• W3020943404 cites W2072367079 @default.
• W3020943404 cites W2075221169 @default.
• W3020943404 cites W2076228685 @default.
• W3020943404 cites W2087852901 @default.
• W3020943404 cites W2092800788 @default.
• W3020943404 cites W2092907887 @default.
• W3020943404 cites W2093006946 @default.
• W3020943404 cites W2093565689 @default.
• W3020943404 cites W2093855402 @default.
• W3020943404 cites W2095131091 @default.
• W3020943404 cites W2101116633 @default.
• W3020943404 cites W2101750864 @default.
• W3020943404 cites W2102035695 @default.
• W3020943404 cites W2107738379 @default.
• W3020943404 cites W2115294057 @default.
• W3020943404 cites W2117119768 @default.
• W3020943404 cites W2119798433 @default.
• W3020943404 cites W2121000910 @default.
• W3020943404 cites W2123759002 @default.
• W3020943404 cites W2124137719 @default.
• W3020943404 cites W2130837075 @default.
• W3020943404 cites W2137520462 @default.
• W3020943404 cites W2141720488 @default.
• W3020943404 cites W2144158174 @default.
• W3020943404 cites W2155792000 @default.
• W3020943404 cites W2160809569 @default.
• W3020943404 cites W2164476527 @default.
• W3020943404 cites W2167716314 @default.
• W3020943404 cites W2179184442 @default.
• W3020943404 cites W2257881775 @default.
• W3020943404 cites W2295865638 @default.
• W3020943404 cites W2296788119 @default.
• W3020943404 cites W2331036577 @default.
• W3020943404 cites W2335463517 @default.
• W3020943404 cites W2526239166 @default.
• W3020943404 cites W2541345182 @default.
• W3020943404 cites W2577678628 @default.
• W3020943404 cites W2589117823 @default.
• W3020943404 cites W2593074975 @default.
• W3020943404 cites W2725319743 @default.
• W3020943404 cites W2725822996 @default.
• W3020943404 cites W2757961091 @default.
• W3020943404 cites W2763020520 @default.
• W3020943404 cites W2770186994 @default.
• W3020943404 cites W2783428982 @default.
• W3020943404 cites W2790791401 @default.
• W3020943404 cites W2790950004 @default.

• next