EXPRESSION OF DRUG METABOLIZING ENZYMES IN CHOROID PLEXUS. IMPLICATIONS IN DETOXIFICATION PROCESSES.
DANIELA GRĂDINARU, ANNE-LAURE MINN, JEAN-MARIE HEYDEL, YVES ARTUR, NICULINA MITREA
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Abstract:

The choroid plexus (CP), which is the principal site of formation of the cerebrospinal fluid (CSF), controls the exchange of many endogenous compounds and exogenous molecules between brain tissue and CSF. We present the changes in mRNA expression and enzymatic activities of UDP-glucuronosyltransferase UGT1A6 isoform and NADPH-cytochrome P450 reductase, after “in vitro” treatment with xenobiotic molecules known to act in the liver as inducers or inhibitors of these drug metabolizing enzymes. Five study groups of male Sprague-Dawley rats were treated separately with: 3-methylcholantrene (3-MC), phenobarbital (PB), dexamethasone (DX), cyclosporine (CY) or paraquat (PQ). Choroidal 1-naphthol glucuronidation activities were significantly induced by 3-MC and PQ administration (354±85 and 257±49 vs. 115±24 nmoles/hour/mg protein, in control group) whereas the other molecules were without effect. UGT1A6 mRNA expression, measured by reverse transcription- polymerase chain reaction (RT-PCR), was 2.3 fold higher after 3-MC treatment and 2.1 fold higher after PQ administration. By contrast, reductasic activities and mRNA expression remained unchanged in the isolated CP, in these experimental conditions. We present for the first time evidences that the CP express these both phase I and II drug metabolizing-enzymes, and that mRNA expression can be regulated by exogenous factors. These results emphasize the role of CP in the metabolic protection to the brain against xenobiotics.

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