Borrisser-Pairó F, Rasmussen M K, Ekstrand B, Zamaratskaia G
1IRTA,Finca Camps i Armet,17121 Monells,Girona,Spain.
2Department of Food Science,Aarhus University,DK-8830 Tjele,Denmark.
Animal. 2015 Apr;9(4):635-42. doi: 10.1017/S1751731114002808. Epub 2014 Dec 3.
Higher accumulation of skatole in the fat of male pigs compared with female pigs might be due to gender-related differences in the rate of skatole degradation. In the present study, skatole metabolites and cytochrome P450 (CYP450) isoforms involved in skatole metabolism were for the first time investigated in hepatic S9 fractions from six male and four female pigs (crossbred Landrace×Yorkshire dams and Duroc boar). Surprisingly, the rates of production of major skatole metabolites were similar in male and female pigs. The most abundant metabolite of skatole was 3-hydroxy-3-methyloxindole (HMOI) followed by 3-methyloxindole and indole-3-carbinol in both male and female S9 fractions. Concentrations of formed HMOI and 3-methyloxindole did not differ between the genders (P=0.124 for HMOI, and P=0.575 for 3-methyloxindole). Indole-3-carbinol formation was higher in S9 fractions from the females compared with male pigs (P=0.0001). Enzyme kinetic parameters were similar for both genders (P>0.05). In both male and female pigs, ellipticine, diallyl sulphide (DAS) and quercetin inhibited HMOI formation, confirming the involvement of CYP1A1 and CYP2E1. The formation of 3-methyloxindole was reduced in the presence of the CYP2E1 inhibitor DAS, and formation of indole-3-carbinol was reduced in the presence of CYP1A1 and CYP2A19 inhibitors. We found only minor differences in skatole metabolism between male and female pigs, particularly the involvement of CYP2C and CYP3A in indole-3-carbinol formation in female but not in male pigs. This is a very essential finding, suggesting the involvement of larger number of CYP450 isoforms in female pigs. On the other hand, indole-3-carbinol is a minor skatole metabolite, and the physiological significance of CYP2C and CYP3A involvement in its formation in female pigs, but not in male pigs, needs to be elucidated. Our results, however, should be interpreted with caution because of the low number of animals and possibility of breed and age effects on skatole metabolism.
与雌性猪相比，雄性猪脂肪中粪臭素的积累量更高，这可能是由于粪臭素降解速率存在性别相关差异。在本研究中，首次在6头雄性猪和4头雌性猪（长白猪×约克夏母猪与杜洛克公猪的杂交后代）的肝脏S9组分中研究了粪臭素代谢产物和参与粪臭素代谢的细胞色素P450（CYP450）同工型。令人惊讶的是，雄性和雌性猪中主要粪臭素代谢产物的生成速率相似。在雄性和雌性S9组分中，粪臭素最丰富的代谢产物是3-羟基-3-甲基氧化吲哚（HMOI），其次是3-甲基氧化吲哚和吲哚-3-甲醇。生成的HMOI和3-甲基氧化吲哚的浓度在性别之间没有差异（HMOI的P = 0.124，3-甲基氧化吲哚的P = 0.575）。与雄性猪相比，雌性猪S9组分中吲哚-3-甲醇的生成更高（P = 0.0001）。酶动力学参数在性别之间相似（P>0.05）。在雄性和雌性猪中，玫瑰树碱、二烯丙基硫醚（DAS）和槲皮素均抑制HMOI的形成，证实了CYP1A1和CYP2E1的参与。在CYP2E1抑制剂DAS存在下，3-甲基氧化吲哚的形成减少，在CYP1A1和CYP2A19抑制剂存在下，吲哚-3-甲醇的形成减少。我们发现雄性和雌性猪之间在粪臭素代谢方面只有微小差异，特别是CYP2C和CYP3A在雌性猪而非雄性猪的吲哚-3-甲醇形成中的参与。这是一个非常重要的发现，表明雌性猪中有更多数量的CYP450同工型参与其中。另一方面，吲哚-3-甲醇是一种次要的粪臭素代谢产物，CYP2C和CYP3A参与雌性猪而非雄性猪中其形成的生理意义需要阐明。然而，由于动物数量较少以及品种和年龄对粪臭素代谢可能产生的影响，我们的结果应谨慎解释。
