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Direct comparison of the thioacetamide and azoxymethane models of Type A hepatic encephalopathy in mice.

著者 Grant S , McMillin M , Frampton G , Petrescu AD , Williams E , Jaeger V , Kain J , DeMorrow S
Gene Expr.2018 Jun 12 ; ():.
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Acute liver failure is a devastating consequence of hepatotoxic liver injury that can lead to the development of hepatic encephalopathy. There is no consensus on the best model to represent these syndromes in mice and therefore the aim of this study was to classify hepatic and neurological consequences of azoxymethane- and thioacetamide-induced liver injury. Azoxymethane-treated mice were euthanized at time points representing absence of, minor and significant stages of neurological decline. Thioacetamidetreated mice had tissue collected at up to 3 days following daily injections. Liver histology, serum chemistry, bile acids and cytokine levels were measured. Reflexes, grip strength measurement and ataxia were calculated for all groups. Brain ammonia, bile acid levels, cerebral edema and neuroinflammation were measured. Finally, and assessments of blood-brain barrier function were performed. Serum transaminases and liver histology demonstrate that both models generated hepatotoxic liver injury. Serum proinflammatory cytokine levels were significantly elevated in both models. Azoxymethanetreated mice had progressive neurological deficits while thioacetamide-treated mice had inconsistent neurological deficits. Bile acids and cerebral edema were increased to a higher degree in azoxymethane-treated mice, while cerebral ammonia and neuroinflammation were greater in thioacetamide-treated mice. Blood-brain barrier permeability exists in both models but was likely not due to direct toxicity of azoxymethane or thioacetamide on brain endothelial cells. In conclusion, both models generate acute liver injury and hepatic encephalopathy but the requirement of a single injection and the more consistent neurological decline makes azoxymethane treatment a better model for acute liver failure with hepatic encephalopathy.
PMID: 29895352 [PubMed - as supplied by publisher]
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