[The effect of rutin and hesperidin on the expression of Nrf2- and AhR-regulated genes and CYP3A1 gene in rats intoxicated with carbon tetrachloride].
Vopr Pitan. 2016 ;85(5):28-35. PMID: 29381299
A S Balakina
The purpose of the study was to determine the effects of rutin (R) and hesperidin (Hes), the main representatives of two most studied subclasses of flavonoids - flavonols and flavanones, on the expression of prototypical Nrf2 and AhR-regulated genes and CYP3A1 gene in rats intoxicated with carbon tetrachloride (CCl4). Investigations were carried out on 5 groups of male Wistar rats with the initial body weight (b.w.) 180-200 g (n=40). Rats of the control group and the 1st experimental group received for 14 days the semisynthetic diet, rats of the 2nd experimental group - the same diet plus R (400 mg/kg b.w.), the animals of the 3rd experimental group received the diet with Hes in the same amount, of the 4th experimental group - diet with R (400 mg/kg b.w.) and Hes (400 mg/kg b.w.). Animals of the experimental groups 24 hours before the end of experiment were injected intraperitoneally CCl4 at a dose of 0.5 ml/kg b.w. in olive oil; rats of the control group were injected equal amount of olive oil. For gene expression assessment the mRNA content of NAD(P)H-quinone oxidoreductase (NQO1), heme oxygenase-1 (Hmox1), Nrf2 (Nrf2), AhR (AhR), CYP1A1, CYP1A2, CYP3A1 andβ-actin (Actb) in rat liver was determined by real-time RT-PCR. The results showed that in rats intoxicated with CCl4, enrichment of the diet with R, but not with Hes, led to a significant increase in the expression of genes Hmox1, NQO1 and CYP3A1. Combined intake of R and Hes with the diet led toadditivity of their action on the expression of Hmox1 gene and to synergism in the effect on the expression of genes NQO1 and CYP3A1. A moderate increase in the levels of expression of AhR and CYP1A2 genes as compared to their expression in rats treated with CCl4 only, CCl4 and R or CCl4 and Hes hasbeen noted. Thus, for the first time on the model of oxidative stress in rats the data have been obtained showing at the gene expression level a synergism of action of two flavonoids - R and Hes, widely present in the daily human diet.