Key result
Macitentan and bosentan induced cytotoxicity and cholestatic disorders in HepaRG cells, sitaxentan was hepatotoxic without cholestatic damage, and ambrisentan was not hepatotoxic.
Why the study?
Do different endothelin receptor antagonists (ambrisentan, macitentan, bosentan, sitaxentan) cause varying degrees of cytotoxicity and cholestatic damage in human HepaRG cells?
Population
Human HepaRG cells (in vitro model)
Design
Preclinical
Authors
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Ambrisentan showed no hepatotoxicity in vitro unlike other ERAs; leaves open whether these differences affect clinical safety.
Do different endothelin receptor antagonists (ambrisentan, macitentan, bosentan, sitaxentan) cause varying degrees of cytotoxicity and cholestatic damage in human HepaRG cells?
In vitro testing reveals that endothelin receptor antagonists have varying profiles of hepatotoxicity and cholestatic potential, with ambrisentan showing no hepatotoxicity compared to macitentan, bosentan, and sitaxentan.
Burbank et al. (2017) studied Pulmonary arterial hypertension (PAH). Endothelin receptor antagonists (ambrisentan, macitentan, bosentan, sitaxentan) was evaluated on Cytotoxicity and cholestatic disorders. Macitentan and bosentan induced cytotoxicity and cholestatic disorders in HepaRG cells, sitaxentan was hepatotoxic without cholestatic damage, and ambrisentan was not hepatotoxic.
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