Analysis Tools
growth/size/body
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• body weights of mice fed chow or chow diet supplement with the ileal bile acid transporter (IBAT) inhibitor (IBATi) SC-435 for 8 weeks are lower than in wild-type mice at 4 weeks of age but become similar to wild-type mice by 12 weeks
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• the liver to body weight ratio is elevated
• treatment with IBATi SC-435 blocks the increase in liver weight
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• the spleen to body weight ratio is increased
• treatment with IBATi SC-435 blocks the increase in spleen weight
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liver/biliary system
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• expression of marker genes for hepatic inflammation are elevated and mice show macrophage infiltration into the liver
• treatment with IBATi SC-435 restores expression of these inflammation markers to wild-type levels
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• mice at 12 weeks of age exhibit features of cholestatic liver injury, with an increase in biliary cell proliferation, macrophage infiltration and collagen deposition
• treatment with IBATi SC-435 attenuates the increase in biliary cell proliferation, macrophage infiltration, and fibrosis
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• mice exhibit elevated serum levels of liver injury markers indicating cholestatic liver injury
• females exhibit more pronounced liver injury than males
• treatment with IBATi SC-435 blocks the increase in liver injury markers
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• the liver to body weight ratio is elevated
• treatment with IBATi SC-435 blocks the increase in liver weight
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• mice at 12 weeks of age show collagen deposition indicating fibrosis
• treatment with IBATi SC-435 attenuates the fibrosis
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hematopoietic system
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• the spleen to body weight ratio is increased
• treatment with IBATi SC-435 blocks the increase in spleen weight
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homeostasis/metabolism
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• in mice fed chow diet
• treatment with IBATi SC-435 blocks this increase
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• in mice fed chow diet or chow diet supplement with IBATi SC-435
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• in mice fed chow diet
• treatment with IBATi SC-435 blocks this increase
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• livers are devoid of hydrophilic 6-hydroxylated alpha-muricholic acids (MCAs)
• livers are enriched in taurochenodeoxycholic acid (TCDCA) and have smaller increases in tauroursodeoxycholic acid (TUDCA) and taurolithocholic acid (TLCA) while taurocholic acid (TCA) is reduced, indicating a significant increase in hydrophobicity of the liver bile acids
• IBATi SC-435 treatment reduces the proportion of TCDCA plus TUDCA, increases the proportion of taurocholic acid (TCA) plus TDCA, but further increases the hydrophobicity index of the liver-associated bile acids
• liver bile acid composition exhibits stronger cytolytic activity in an RBC lysis assay than in wild-type, indicating that liver bile acids are more cytotoxic
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• mice show an increase in serum bile acids
• hepatic bile acid content is increased
• treatment with IBATi SC-435 blocks the increase in serum bile acids and prevents the increase in liver bile acid retention
• total liver bile acid levels are lower in males versus females, however hydrophobicity of the liver bile acids is similarly elevated in male and female mice and in IBATi-treated mice
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immune system
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• the spleen to body weight ratio is increased
• treatment with IBATi SC-435 blocks the increase in spleen weight
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• expression of marker genes for hepatic inflammation are elevated and mice show macrophage infiltration into the liver
• treatment with IBATi SC-435 restores expression of these inflammation markers to wild-type levels
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