Modulation and absorption of xenobiotics: the synergistic role of CYP450 and P-gp activities in cancer and neurodegenerative disorders.

Abstract:

:P-glycoprotein (P-gp) is involved in MDR and in neurodegenerative disorders such as Parkinson disease (PD), Alzheimer disease (AD) and epilepsy. Cytochrome P450 enzymes (CYP450s) catalyze the metabolism of a wide variety of endogenous and exogenous compounds including xenobiotics, drugs, environmental toxins, steroids, and fatty acids. P-gp substrates, inhibitors and inducers should be designed and developed studying interacting mechanism with both P-gp an CYP450 enzymes before they could be employed in MDR and/or in neurodegenerative disorders. Here, the ex vivo rat everted gut sac assay has been proposed as an immediate approach to simultaneously study metabolism and transport of drugs. Elacridar, verapamil and cyclosporine A (CsA), P-gp inhibitor, substrate and modulator respectively, have been tested to validate this ex vivo approach. The new model have been used yet to develop our ligands MC18, MC266 and MC80, both as potential drugs for MDR and radiotracers for diagnosis of neurodegenerative disorders. Herein, a comparative evaluation of transport and metabolic results, by using in vitro, ex vivo and in vivo assays, is reported.

journal_name

Curr Drug Metab

journal_title

Current drug metabolism

authors

Inglese C,Perrone MG,Berardi F,Perrone R,Colabufo NA

doi

10.2174/138920011798357015

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

702-12

issue

8

eissn

1389-2002

issn

1875-5453

pii

BSP/CDM/E-Pub/000146

journal_volume

12

pub_type

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