ININFA   02677
INSTITUTO DE INVESTIGACIONES FARMACOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Modification in the expression of brain ABC transporters during acute acetaminophen intoxication in mice. .
Autor/es:
GHANEM CI.; MANAUTOU JE
Lugar:
Cambridge
Reunión:
Jornada; Northeast Regional Chapter of the Society of Toxicology; 2013
Institución organizadora:
NESOT
Resumen:
hanges in gene and protein expression of liver ABC transporters have been previously described during acute acetaminophen (APAP) intoxication. However, the effect of hepatotoxic doses of this drug on brain ABC transporters has never been studied. The aim of the present study was to evaluate the effect of acute APAP intoxication on the expression of main brain ABC transporters in male mice. For this purpose, male C57BL6 mice were divided into two groups. The APAP group received a toxic dose of APAP (400mg/Kg, i.p), while the control group received just saline vehicle. 24 h later, the brain was removed and protein expression of Mrp1-Mrp5, Bcrp and P-gp was determined by Western blotting using total brain homogenate. mRNA expression for these ABC transporters was also assayed by real time PCR. The results show that APAP treatment increases significantly the expression of brain P-gp, Mrp2 and Mrp4. The protein expression values in the APAP group were 195, 293 and 38 % greater than in control brains for P-gp, Mrp2 and Mrp4, respectively. No changes were detected in the expression of Bcrp, Mrp1 and Mrp5, while Mrp3 expression was no detectable in brain of both groups of mice. The increased protein expression for P-gp and Mrp4 correlated well with changes in mRNA expression (48 and 85 % higher than controls, respectively). There was also concordance between protein and mRNA expression for Bcrp, Mrp1, Mrp3, and Mrp5, which did not change by APAP intoxication. On the other hand, Mrp2 mRNA expression was decreased in the APAP group by 60%, which is in contrast to its significant increase in protein expression. In conclusion, acute APAP intoxication induces protein expression of several brain ABC transporters. While induction of brain P-gp and Mrp4 protein expression by APAP appears to be through a transcriptional mechanism, the changes in Mrp2 expression may involve posttranscriptional events. The functional consequences of these changes in brain ABC transporters by APAP deserve further attention.