Abstracts

RATIONALE: MDR-1 gene-encoded P-glycoprotein (P-170) is involved in multiple-drug resistance mechanism observed in cancer and it has been recently described to be expressed in brain of patients with refractory epilepsy (Tishler 1995; Lazarowski 1999; Sisodiya 2002). We have previously demonstrated that the expression of P-170 was induced after 4 days of treatment with i.p administered proconvulsivant drug 3-mercaptopropionic acid (MP), in brain vessel walls, astrocytes, foot process astrocytes and lightly in surrounding neurons (Lazarowski et al. 2002) The aim of this study is to analyze if longer times of MP treatment can induce a greater P-170 expression in neurons.
METHODS: Male Wistar rats (250-300g) were daily administered with 45mg/kg i.p. of MP during 4 days (MP-4) and 7 days (MP-7). Rats daily injected with saline were used as controls. One day after the las injection, rats were deeply anaesthetized with chloral hydrate (300 mg/kg) and fixed by perfusion. Brains were dissected and processed for immunohistochemistry using monoclonal anti-P170 as primary antibody and the peroxidase-antiperoxidase technique.
RESULTS: Brain sections of MP-4 treated animals showed intense P-170 expression in striatum and cerebral cortex. Immuno-reactivity was prominent in the capillary endothelium and surrounding astrocytes, and also evident although less intense in few neuron fibers. In MP-7 extensive neuronal areas were stained at the same brain regions, and the imges shoed sparred immunostaining on neurons, increasing higly the intensity near the vessels.
In control animals, P-170 expression was minimal, showing a light and spared labelling on few blood vessels.
CONCLUSIONS: These results showed a differential pattern of expression of MDR-1 gene (P-170) in brain MP-treated rats in 4 and 7 days.
A longer time of MP treatment induced more extensive neuronal MDR-1 gene expression.
It is the first experimental model of MDR-1 gene neuronal expression induced by proconvulsivant drug treatment.
References:
Tishler D et al : Epilepsa 1995; 36:1-6
Lazarowski A et al.: Pediatric Neurology 1999, 21:731-734
Sisodiya SM. et al.: Brain 2002, 125: 22-31
Lazarowski A. et al.: 2[degree]Latinamerican Congress of Epilepsy 2002. Brazil.
[Supported by: University of Buenos Aires (UBACYT B-033), CONICET and Ministerio de Salud, Argentina]; (Disclosure: Salary - ------------, Grant - UBACYT B33, CONICET and Ministerio de Salud, Argentina, Equity - ----------------, Consulting - ----------------, Ownership - ----------------, Materials - -------------------, Stock - ------------------, Royalties - -------------------, Honoraria - -------------------, Other - ------------------------)