Speen, Adam M.; Hoffman, Jessica R.; Kim, Hye-Young H.; Escobar, Yael N.; Nipp, Grace E.; Rebuli, Meghan E.; Porter, Ned A.; Jaspers, Ilona published the artcile< Small Molecule Antipsychotic Aripiprazole Potentiates Ozone-Induced Inflammation in Airway Epithelium>, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, the main research area is antipsychotic aripiprazole ozone inflammation airway epithelium.
Inhaled ground level ozone (O3) has well described adverse health effects, which may be augmented in susceptible populations. While conditions, such as pre-existing respiratory disease, have been identified as factors enhancing susceptibility to O3-induced health effects, the potential for chem. interactions in the lung to sensitize populations to pollutant-induced responses has not yet been studied. In the airways, inhaled O3 reacts with lipids, such as cholesterol, to generate reactive and electrophilic oxysterol species, capable of causing cellular dysfunction and inflammation. The enzyme regulating the final step of cholesterol biosynthesis, 7-dehydrocholesterol reductase (DHCR7), converts 7-dehydrocholesterol (7-DHC) to cholesterol. Inhibition of DHCR7 increases the levels of 7-DHC, which is much more susceptible to oxidation than cholesterol. Chem. anal. established the capacity for a variety of small mol. antipsychotic drugs, like Aripiprazole (APZ), to inhibit DHCR7 and elevate circulating 7-DHC. Our results show that APZ and the known DHCR7 inhibitor, AY9944, increase 7-DHC levels in airway epithelial cells and potentiate O3-induced IL-6 and IL-8 expression and cytokine release. Targeted immune-related gene array anal. demonstrates that APZ significantly modified O3-induced expression of 16 genes, causing dysregulation in expression of genes associated with leukocyte recruitment and inflammatory response. Addnl., we find that APZ increases O3-induced IL-6 and IL-8 expression in human nasal epithelial cells from male but not female donors. Overall, the evidence we provide describes a novel mol. mechanism by which chems., such as APZ, that perturb cholesterol biosynthesis affect O3-induced biol. responses.
Chemical Research in Toxicology published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (C1R). 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol.
Referemce:
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