Abstract

role of bile acids in the progression of HE, mice were fed a diet enriched in the bile acid sequestrant cholestyramine, or the bile acids cholic acid (CA), deoxycholic acid (DCA) or ursodeoxycholic acid (UDCA) for 3 days prior to AOM injection. Subsequent assessment of neurological decline and liver damage was performed in these mice. The dose of bile acids given has previously been shown to not cause liver damage. Results: Total bile acids were increased in the brains of mice after AOM injection compared to controls. In parallel, fluorescently-derived bile acids were increased in the brains of AOM mice, suggesting that bile acids are entering from the periphery. Cholestyramine feeding reduced both the serum and brain bile acid levels and delayed the neurological decline associated with acute liver failure without any significant differences in liver damage. In contrast, feeding with CA and DCA worsened the AOM-induced neurological decline and significantly decreased the time taken to reach coma, with DCA having the greatest effect while UDCA feeding had no effect. Conclusions: These data indicate that circulating bile acids may be pathological in the brain during the course of HE, although precisely how they are dysregulating normal brain function is unknown. Strategies to minimize the total bile acid content in the serum may improve the outcome of patients with neurological symptoms associated with liver failure.

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