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• W1981068051 abstract "Abstract Background & Aims Variations in intestinal microbiota may influence acetaminophen metabolism. This study aimed to determine whether intestinal microbiota are a source of differential susceptibility to acetaminophen‐induced hepatotoxicity. Methods Conventionally housed C3H/HeH ( CH ) and C3H/HeH germ‐free ( GF ) mice were administered a 200 mg/kg IP dose of acetaminophen. The severity of hepatotoxicity at 8 h was assessed by histology and biochemical indices. A urinary metabolic profile was obtained using 1 H‐ NMR . Baseline hepatic glutathione content and CYP 2E1 expression were quantified. An additional group of C3H/HeJ ( LPS ‐r) mice were assessed to determine the contribution of LPS / TLR 4 signalling. Results Baseline glutathione levels were significantly reduced ( P = 0.03) in GF mice. CYP2E1 mRNA expression and protein levels were not altered. Interindividual variability did not differ between GF and CH groups. No significant differences in the extent of hepatocellular injury (ALT or percentage necrosis) were demonstrated. However, a milder acute liver failure (ALF) phenotype was shown in GF compared with CH mice, with reduced plasma bilirubin and creatinine and increased blood glucose. Differential acetaminophen metabolism was demonstrated. GF mice displayed a higher urinary acetaminophen‐sulphate:glucuronide ratio compared with CH ( P = 0.01). Urinary analysis showed metabolic differentiation of GF and CH groups at baseline and 8 h (cross‐validated anova P = 1 × 10 ‐22 ). Interruption of TLR4 signalling in LPS‐r mice had additional protective effects. Conclusion Variations in intestinal microbiota do not fully explain differential susceptibility to acetaminophen‐induced hepatotoxicity. GF mice experienced some protection from secondary complications following acetaminophen overdose and this may be mediated through reduced TLR 4/ LPS signalling." @default.
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• W1981068051 date "2014-10-08" @default.
• W1981068051 modified "2023-10-03" @default.
• W1981068051 title "The role of intestinal microbiota in murine models of acetaminophen‐induced hepatotoxicity" @default.
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• W1981068051 doi "https://doi.org/10.1111/liv.12689" @default.
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