Gene expression profiling of rat liver reveals a mechanistic basis for ritonavir-induced hyperlipidemia

摘要: The molecular mechanisms of action a HIV protease inhibitor, ritonavir, on hepatic function were explored genomic scale using microarrayscomprisinggenesexpressedintheliverof Sprague–Dawleyrats(Rattusnorvegicus).Analysesofhepatictranscriptionalfingerprintsled to the identification several key cellular pathways affected by ritonavir treatment. These effects compared compendium gene expression responses for 52 unrelated compounds and other inhibitors, including atazanavir two experimental compounds. We identified genes involved in cholesterol fatty acid biosynthesis, as well breakdown, whose expressions regulated opposite manners bezafibrate, hypolipidemic agonist peroxisome proliferator-activated receptor α. Ritonavir also upregulated multiple proteasomal subunit transcripts ubiquitination, consistent with its known inhibitory effect activity. tested three inhibitors addition ritonavir. Atazanavir did not impact ubiquitin or expression, although impacted both sterol regulatory element-binding protein-activated genes, similar Identification metabolic that are will enable us understand better downstream thus leading drug design an effective method mitigate side this important class therapeutics.