Regulation of Porcine Hepatic Cytochrome P450 by Chicory Root - Implication of Boar Taint

Summary

Dietary components have been shown to affect the hepatic detoxification system. Hepatic clearance of xenobiotics is performed in two steps, Phase I and II. Phase I is usually carried out by enzymes belonging to the cytochrome P450 (CYP) family, while Phase II is carried out by a more diverse group. Phase I and II enzymes are extensively studied for their importance in drug clearance and in pigs for their impact on the occurrence of boar taint. It is generally believed that sufficient Phase I and II metabolism of the boar taint compounds, skatole and androstenone, diminish the occurrence of tainted meat from sexually mature male pigs. Moreover, dietary chicory root has been shown to decrease the occurrence of boar taint. The present PhD study was carried out order to investigate the regulation of Phase I and II enzymes by chicory root. Sexually mature male pigs were fed chicory root for the ast 16 days before slaughter. They showed increased mRNA expression of CYP1A2, 2A19, 2D25, 2E1, 3A29 as well as 3β hydroxysteroid dehydrogenase (3β-HSD). A simultaneous increase in protein expression of CYP1A2, 2A19 and 3β-HSD as well as increased activities of CYP1A2, 2A and 3A were shown. No effect was shown on the expression of the investigated Phase II enzyme, sulfotransferase 2A1 (SULT2A1). Chicory feeding had no effect on skatole accumulation in fat, while the androstenone concentration found in the group of chicory fed pigs were lower than in the control group. Additionally, chicory feeding had no effect on testosterone, estradiol and insulin-like growth factor 1 (IGF-1) in plasma. The obtained in vivo results of chicory feeding are in contrast to the results obtained in vitro using primary porcine hepatocytes. Porcine hepatocytes were isolated from female piglets and treated with a methanolic extract of chicory root for 24 hours. This treatment down regulated the mRNA expression of CYP1A2, 2C33, 2D25 and 3A29. In comparison standard CYP inducers (β-naphthoflavone and dexamethasone) and secondary plant metabolites (artemisinin and scoparone) increased the mRNA expression of the same CYPs. As the occurrence of boar taint is associated with sexually mature male pigs, a comparison of the constitutive CYP expression and activity between genders was also included. It was shown that female pigs, in comparison to entire male pigs, had greater mRNA expression of CYP1A2, 2A19 and 3A29, while no differences were observed in protein expression. Likewise female pigs had greater CYP1A2, 2A and 2C enzyme activity. The absolute activities found in the chicory fed male pigs were comparable to the activities found in the female pigs. In conclusion, the results presented in this PhD thesis uggest that chicory feeding can be used to lower the occurrence of boar taint. This is partly based on the finding that chicory feeding increases CYP activity to levels comparable with female pigs, as well as the effects shown on the metabolism of androstenone.