Expression and activity of CYP 1A1 in different brain regions of control and beta-naphthoflavone-treated pigs

Abstract

Expression and activity of CYP 1A1 in different brain regions of control and beta-naphthoflavone-treated pigs Gervasi, P.G.1, Chirulli, V.1, Zaghini, A.2, Vaccaro, E.3, Fiorio, R.3, Longo, V.3, Marvasi, L.2 1 Ins. Clinical Physiology, Metabolism, Pisa, Italy; 2 Bologna University, Patologia Veterinaria, Bologna, Italy; 3 Ins. Clinical Physiology, Metabolism, PISA, Italy The expression of the cytochrome P450 1A1 (CYP 1A1) and its related activities along with the Ah Receptor were investigated in liver and brain regions from control pigs and pigs treated with beta-naphthoflavone (30 mg/kg i.p. for 4 days). By RT-PCR analysis, using specific primers, it was demonstrated that mRNA of CYP 1A1 and AhR were expressed, although at different extent, in the liver, cortex, midbrain and cerebellum. However, the beta-naphthoflavone treatment had no apparent effect on expression pattern of this isoform, unlike liver, in any brain region. Then, some enzymatic activities (ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase), known markers for the CYP 1A1/2, were studied in microsomes of liver and microsomes and mitochondria of cortex, midbrain and cerebellum from control and beta-naphthoflavone treated pigs. The enzymatic analysis revealed a presence of these activities about 3-4 times higher in mitochondria than in microsomes from all the brain regions examined. However, in contrast to the behaviour of the liver, beta-naphthoflavone treatment did not induce the cerebral activities. Despite the presence of AhR, the CYP1A1 in the pig brain was resistant to beta-naphthoflavone induction suggesting that there is a different regulation mechanism of this enzyme between the brain and liver

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