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• W3033112798 abstract "Aims: Drug-induced liver injury, especially acetaminophen (APAP)-induced liver injury, is a leading cause of liver failure worldwide. Mouse models were used to evaluate the effect of microelement selenium levels on the cellular redox environment and consequent hepatotoxicity of APAP. Results: APAP treatment affected mouse liver selenoprotein thioredoxin reductase (TrxR) activity and glutathione (GSH) level in a dose- and time-dependent manner. Decrease of mouse liver TrxR activity and glutathione level was an early event, and occurred concurrently with liver damage. The decreases in the GSH/glutathione disulfide form (GSSG) ratio and TrxR activity, and the increase of protein S-glutathionylation were correlated with the APAP-induced hepatotoxicity. Moreover, in APAP-treated mice both mild deprivation and excess supplementation with selenium increased the severity of liver injury compared with those observed in mice with normal dietary selenium levels. An increase in the oxidation state of the TrxR-mediated system, including cytosolic thioredoxin1 (Trx1) and peroxiredoxin1/2 (Prx1/2), and mitochondrial Trx2 and Prx3, was found in the livers from mice reared on selenium-deficient and excess selenium-supplemented diets upon APAP treatment. Innovation: This work demonstrates that both Trx and GSH systems are susceptible to APAP toxicity in vivo, and that the thiol-dependent redox environment is a key factor in determining the extent of APAP-induced hepatotoxicity. Dietary selenium and selenoproteins play critical roles in protecting mice against APAP overdose. Conclusion: APAP treatment in mice interrupts the function of the Trx and GSH systems, which are the main enzymatic antioxidant systems, in both the cytosol and mitochondria. Dietary selenium deficiency and excess supplementation both increase the risk of APAP-induced hepatotoxicity." @default.
• W3033112798 created "2020-06-12" @default.
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• W3033112798 date "2021-06-10" @default.
• W3033112798 modified "2023-10-01" @default.
• W3033112798 title "Selenium Status in Diet Affects Acetaminophen-Induced Hepatotoxicity <i>via</i> Interruption of Redox Environment" @default.
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• W3033112798 doi "https://doi.org/10.1089/ars.2019.7909" @default.
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