[Effect of separate and combined intake of rutin and hesperidin on the activity and gene expression of cytochrome P450 isoforms 1A and 3A in rat liver].

Abstract

The main molecular mechanisms of the protective effect of minor bioactive compounds (BAC) of food, including rutin and hesperidin, along with antiradical and antioxidant activity, include their interaction with transcription factors modulating the functional state of the organism defense systems, one of which is the system of xenobiotic metabolizing enzymes. However, the data on their combined action are limited. The aim of the research was to study the effect of rutin and hesperidin on the activity and gene expression of cytochrome P450 isoforms 1A and 3A (CYP1A1, CYP1A2, CYP3A) in rat liver at their separate and combined intake. Material and methods. The study was carried out using 4 groups of 6 male Wistar rats with initial body weight 225±5 g. For 14 days the rats of the control group received a standard semi-synthetic diet. Rutin and hesperidin were administered separately or together at a calculated daily dose of 400 mg per 1 kg body weight. CYP1A1 and CYP1A2 activities were determined spectrofluorimetrically in liver microsomal fraction, CYP3A activity - by high-performance liquid chromatography. Gene expression was analyzed by real-time reverse transcription polymerase chain reaction. Results. Dietary intake of rutin and hesperidin did not significantly alter the activity of the studied enzymes of xenobiotic metabolism, but had an inducing effect on CYP1A1 and CYP1A2 genes, expression of which statistically significant increased both at separate and combined intake. The expression of CYP3A1 gene did not differ from control values at intake of rutin alone, but considerably and statistically significant decreased in the presence of hesperidin in the diet. An increase in transcription factor AhR gene expression was noted, moreover the expression in the group receiving rutin + hesperidin was significantly reduced in relation to the group receiving rutin alone. Conclusion. Combined intake of flavonoids (rutin and hesperidin) has a modulating effect on enzymes of xenobiotic metabolism at the level of their gene expression.