1. In this study, the expression and inducibility of CYP2C33, 2C42, 2C49, 2B22, 3A22, 3A29 and 3A46 were investigated at activity and /or transcriptional level in liver, kidney, small intestine, respiratory and olfactory nasal mucosa of control and phenobarbital (PB)-treated pigs. 2. PB treatment resulted in an up-regulation of mRNA levels of all analysed CYPs in liver, of CYP2C42 and 2C49 in kidney, of CYP2C42, 2C49, CYP2B22 and CYP3As in small intestine. 3. In liver microsomes from PB-treated pigs, these transcriptional activations were accompanied by an increase of various marker activities of human CYP2B6, CYP3As CYP2C9, CYP2C19. Among the extrahepatic tissues, a significant induction by PB was observed only in kidney for the marker activities of CYP2C9. 4. Taken together, our results demonstrated that the PB administration in pig induced at least in liver, in addition to CYP2B22 and 3As, the expression of CYP2C33, 2C42 and 2C49 at transcriptional and activity levels. 5. Furthermore our findings showed that the catalytic activities of porcine CYP2Cs are different amongst those observed and with respect to the human counterparts. Thus, the use of pig as a model for humans in studies with drugs either substrates and/or inducers of CYP2Cs should be considered carefully.
Expression and inducibility by phenobarbital of CYP2C33, CYP2C42, CYP2C49, CYP2B22, and CYP3as in porcine liver, kidney, small intestine, and nasal tissues
Beffy P;
2010
Abstract
1. In this study, the expression and inducibility of CYP2C33, 2C42, 2C49, 2B22, 3A22, 3A29 and 3A46 were investigated at activity and /or transcriptional level in liver, kidney, small intestine, respiratory and olfactory nasal mucosa of control and phenobarbital (PB)-treated pigs. 2. PB treatment resulted in an up-regulation of mRNA levels of all analysed CYPs in liver, of CYP2C42 and 2C49 in kidney, of CYP2C42, 2C49, CYP2B22 and CYP3As in small intestine. 3. In liver microsomes from PB-treated pigs, these transcriptional activations were accompanied by an increase of various marker activities of human CYP2B6, CYP3As CYP2C9, CYP2C19. Among the extrahepatic tissues, a significant induction by PB was observed only in kidney for the marker activities of CYP2C9. 4. Taken together, our results demonstrated that the PB administration in pig induced at least in liver, in addition to CYP2B22 and 3As, the expression of CYP2C33, 2C42 and 2C49 at transcriptional and activity levels. 5. Furthermore our findings showed that the catalytic activities of porcine CYP2Cs are different amongst those observed and with respect to the human counterparts. Thus, the use of pig as a model for humans in studies with drugs either substrates and/or inducers of CYP2Cs should be considered carefully.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
