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Of all tissues, the kidney has the greatest overall increase in ET concentration with a 4.8-fold increase in kidney ET at 28 days of high dose (ET++) relative to control, while liver and whole blood of the same group only increased by 2.5- and 3.3-fold relative to control animals (Fig

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Dysregulation in the FXR and TGR5 signaling pathways leads to hepatocyte toxicity due to an increase in primary bile acids like cholic acid (CA) and chenodeoxycholic acid (CDCA), as well as a decrease in secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA), which in turn triggers microbiota dysbiosis and MASLD pathogenesis [249]