1750-45-4, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, the author is Ghonem, Nisanne and a compound is mentioned, 1750-45-4, 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, introducing its new discovery.
Treprostinil Improves Hepatic Cytochrome P450 Activity during Rat Liver Transplantation
Background: Cytochrome P450 (CYP450) activity is an important indicator of liver graft function. CYP450 activity is altered by pro-inflammatory cytokines, which are associated with ischemia-reperfusion (I/R) injury during orthotopic liver transplantation (OLT). Treprostinil, an FDA-approved prostacyclin analog, ameliorated cold I/R injury during rat OLT. We hypothesized that treprostinil would improve CYP450 activity in liver graft during cold I/R injury post-OLT. Methods: OLT was performed in syngeneic male Lewis rats with 18 h graft preservation in cold UW solution. Donor and recipients received treprostinil (100 ng/kg/min) or matching placebo for 24 h before and up to 48 h post-OLT. Liver graft mRNA and protein expression of CYP450 isoforms were analyzed by qRT-PCR and Western blot analysis, respectively. The formation rates of 1-hydroxymidazolam and 6beta-hydroxytestosterone, 6-hydroxychlorzoxazone, 2alpha- and 16alpha-hydroxytestosterone in liver graft microsomes served as markers for CYP3A, CYP2E1, and CYP2C11 activity, respectively, and were measured by LC-MS. Results: Treprostinil significantly decreased serum ALT and AST levels at 6-48 h after OLT, compared to placebo. The expressions of TNFalpha and IFNgamma mRNA in the liver graft were significantly inhibited in the treprostinil-treated group at 1 h post-reperfusion. Treprostinil restored CYP2E1 protein expression to that of normal liver and significantly improved CYP3A activity to more than two-fold of placebo early post-OLT. Conclusions: Treprostinil significantly ameliorated hepatic injury, reduced expression of pro-inflammatory cytokines, and improved CYP450 activity in liver graft early post-OLT. These findings suggest that treprostinil has the potential to serve as a therapeutic option to protect liver graft function against I/R injury during clinical OLT.
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Reference£º
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem