ABSTRACT
The purpose of the study was to determine the effects of curcumin (CUR) and quercetin (QUER) on the expression of genes and activity of prototypical Nrf2/ARE- and AhR/ XRE-regulated enzymes. Investigation was carried out on male Wistar rats with initial body weight (230-235 g b.w.) that received for 14 days CUR (200 mg/kg b.w.) and QUER (200 mg/kg b.w.) separately or in combination within the standard semi-synthetic diet. The expression of genes and activity of Nrf2/ARE - regulated enzymes - heme oxygenase- 1(HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), AhR/XRE-regulated CYP1A1, CYP1A2 enzymes and the mRNA level of transcription factors Nrf2 and AhR were determined in rats liver. Also the expression of gene CYP3A1 and activity of CYP3A, UDP-glucuronosyltransferase, glutathione transferase were studied in rats liver. Along with this the total antioxidant activity (AOA), malondialdehyde and lipid hydroperoxides levels were determined in blood plasma and liver. The reduced and oxidized glutathione level, total and unsedimentable activity of lysosomal enzymes were investigated in rats' liver. QUER, especially in combination with CUR, increased the AOA of blood plasma and reduced the content of lipid hydroperoxides in it. CUR and QUER did not affect NQO1 activity, but the combined action caused an increase in the HO-1 activity without affecting the expression of the corresponding gene (Hmox1) and Nrf2 gene. CUR and, to a lesser extent QUER, had a strong inducing effect on CYP1A1, CYP1A2, CYP3A activity, but only the CYP1A1 activation was accompanied by the induction of CYP1A1 gene. The inducing effect of CUR and QUER on the activity of CYP450 enzymes greatly enhanced by their combined action. Membrane stabilizing action of CUR and QUER was also strongly expressed under its combined intake. Thus, we can conclude that CUR and QUER, especially in combination, contribute to the protective and adaptive capacity.
ABSTRACT
The intragastric administration to male Wistar rats of T-2 toxin at 1-1.3 mg/kg body weight for 7 days caused a sharp decrease in the liver activity of lysosomal enzymes: beta-galactosidase, beta-N-acetylglucosaminidase, alpha-mannosidase, cathepsins A, B, C and D and in the activity of enzymes of the 1st phase of metabolism of xenobiotics--aniline hydroxylase and carboxylesterase, as well as in the cytochrome P-450 level. At the same time, the subacute toxic effect of T-2 toxin was manifested in a significant increase in the activity of epoxide hydrolase and an enzyme of the 2nd phase of metabolism of xenobiotics--UDP-glucuronosyltransferase. A possible mechanism of the observed enzymological changes is discussed.
