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- W3132321824 abstract "Trovafloxacin (TVX) is associated with idiosyncratic drug-induced liver injury (iDILI) and inflammation-mediated hepatotoxicity. However, the inflammatory stress-regulated mechanisms in iDILI remain unclear. Herein, we elucidated the novel role of tumor-necrosis factor alpha (TNFα), an inflammatory stress factor, in TVX-induced in vitro hepatotoxicity and synergistic toxicity. TVX specifically induced synergistic toxicity in HepG2 cells with TNFα, which inhibits autophagy. TVX-treated HepG2 cells induced protective autophagy by inhibiting the expression of mTOR signaling proteins, while ATG5 knockdown in HepG2 cells, responsible for the impairment of autophagy, enhanced TVX-induced toxicity due to the increase in cytochrome C release and JNK pathway activation. Interestingly, the expression of mTOR signal proteins, which were suppressed by TVX, disrupted the negative feedback of the PI3K/AKT pathway and TNFα rebounded p70S6K phosphorylation. Co-treatment with TVX and TNFα inhibited protective autophagy by maintaining p70S6K activity, which enhanced TVX-induced cytotoxicity. Phosphorylation of p70S6K was inhibited by siRNA knockdown and rapamycin to restore TNFα-inhibited autophagy, which prevented the synergistic effect on TVX-induced cytotoxicity. These results indicate that TVX activates protective autophagy in HepG2 cells exposed to toxicity and an imbalance in negative feedback regulation of autophagy by TNFα synergistically enhanced the toxicity. The finding from this study may contribute to a better understanding of the mechanisms underlying iDILI associated with inflammatory stress." @default.
- W3132321824 created "2021-03-01" @default.
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- W3132321824 date "2021-05-01" @default.
- W3132321824 modified "2023-09-22" @default.
- W3132321824 title "TNFα enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy" @default.
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- W3132321824 cites W1979952830 @default.
- W3132321824 cites W1983835791 @default.
- W3132321824 cites W1985366099 @default.
- W3132321824 cites W1995966034 @default.
- W3132321824 cites W2002636911 @default.
- W3132321824 cites W2008553918 @default.
- W3132321824 cites W2009813640 @default.
- W3132321824 cites W2013381376 @default.
- W3132321824 cites W2019181491 @default.
- W3132321824 cites W2028348804 @default.
- W3132321824 cites W2033617878 @default.
- W3132321824 cites W2039193709 @default.
- W3132321824 cites W2049789320 @default.
- W3132321824 cites W2057614743 @default.
- W3132321824 cites W2060793088 @default.
- W3132321824 cites W2061030289 @default.
- W3132321824 cites W2065237367 @default.
- W3132321824 cites W2066851223 @default.
- W3132321824 cites W2067019627 @default.
- W3132321824 cites W2067656165 @default.
- W3132321824 cites W2068696470 @default.
- W3132321824 cites W2069744105 @default.
- W3132321824 cites W2073820873 @default.
- W3132321824 cites W2076769172 @default.
- W3132321824 cites W2078184757 @default.
- W3132321824 cites W2085025875 @default.
- W3132321824 cites W2085143181 @default.
- W3132321824 cites W2087835012 @default.
- W3132321824 cites W2089827602 @default.
- W3132321824 cites W2101020543 @default.
- W3132321824 cites W2101220947 @default.
- W3132321824 cites W2115888489 @default.
- W3132321824 cites W2116935685 @default.
- W3132321824 cites W2120595804 @default.
- W3132321824 cites W2123759002 @default.
- W3132321824 cites W2124857644 @default.
- W3132321824 cites W2126028929 @default.
- W3132321824 cites W2129585918 @default.
- W3132321824 cites W2129712803 @default.
- W3132321824 cites W2131333624 @default.
- W3132321824 cites W2138418865 @default.
- W3132321824 cites W2153214289 @default.
- W3132321824 cites W2159632264 @default.
- W3132321824 cites W2160444874 @default.
- W3132321824 cites W2160736876 @default.
- W3132321824 cites W2163553267 @default.
- W3132321824 cites W2169144885 @default.
- W3132321824 cites W2295124356 @default.
- W3132321824 cites W2302134090 @default.
- W3132321824 cites W2540781052 @default.
- W3132321824 cites W2557647482 @default.
- W3132321824 cites W2560000662 @default.
- W3132321824 cites W2606513998 @default.
- W3132321824 cites W2752326209 @default.
- W3132321824 cites W2768071163 @default.
- W3132321824 cites W2771826181 @default.
- W3132321824 cites W2811378860 @default.
- W3132321824 cites W2883981538 @default.
- W3132321824 cites W2892278078 @default.
- W3132321824 cites W2897077524 @default.
- W3132321824 cites W2914225706 @default.
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- W3132321824 cites W2949603991 @default.
- W3132321824 cites W2965449651 @default.
- W3132321824 cites W2992985193 @default.
- W3132321824 cites W3004591916 @default.
- W3132321824 cites W3085021059 @default.
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- W3132321824 doi "https://doi.org/10.1016/j.toxlet.2021.02.009" @default.
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- W3132321824 hasPublicationYear "2021" @default.
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