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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/46379

Title: Evaluation of hepatic activity of immunomodulatory compounds and GSK3 inhibitors
Other Titles: Evaluación de la actividad de los metabolitos hepáticos derivados de compuestos inmunomodulares e inhibidores de GSK3
Authors: Pérez del Palacio, José
Direction: Vicente Pérez, María Francisca
Gálvez Peralta, Julio Juan
Collaborator: Universidad de Granada. Departamento de Farmacología
Issue Date: 2017
Submitted Date: 27-Apr-2017
Abstract: Nitric-oxide synthase (NOS), the enzyme responsible for mammalian nitric oxide (NO) generation, and cytochrome P450 (CYP450), the main enzymes involved in drug metabolism, share striking similarities. First and foremost, both are heme-thiolate proteins, which employ the same prosthetic group to perform similar chemistry. Moreover, they share the same diflavoprotein reductase as redox partner. Therefore, it makes sense that cytochrome P450 drug-mediated biotransformations might play an important role in the pharmacological modulation of NOS. In this work, we have undertaken an integrated in vitro assessment of the hepatic metabolism and NO modulation of previously described dual inhibitors (imidazoles and macrolides) of these enzymes, in order assess the involvement of CYP450 activities in the production of NO. From the experience acquired during this aim, we developed a validated high-throughput screening (HTS) approach in 96-well plate format for the assessment and discovery of molecules with anti-inflammatory/immunomodulatory activity. The in vitro models were based on the quantitation of nitrite levels in lipopolysaccharide (LPS) stimulated RAW 264.7 murine macrophages and interleukin-8 (IL-8) in Caco-2 cells stimulated with interleukin 1β (IL-1β)
Sponsorship: Tesis Univ. Granada. Programa Oficial de Doctorado en: Medicina Clínica y Salud Pública
Publisher: Universidad de Granada
Keywords: Oxido nítrico
Sistema nervioso central
UDC: 611.018
URI: http://hdl.handle.net/10481/46379
ISBN: 9788491631965
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Pérez del Palacio, J. Evaluation of hepatic activity of immunomodulatory compounds and GSK3 inhibitors. Granada: Universidad de Granada, 2017. [http://hdl.handle.net/10481/46379]
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