[Effects of rutin on protective capacity in rats].

The purpose of the study was to determine effects of rutin dietary administration on the activity of xenobiotic-metabolizing enzymes and antioxidant status. The study has been carried out on 3 groups of male Wistar rats (n = 8 in each), with initial body weight 100-120 g. Animals of the control group (1st group) received standard semi-synthetic diet, the experimental groups--the same diet with rutin in the amount of 40 mg/kg b.w. (2nd group) or 400 mg/kg b.w. (3rd group). The duration of the experiment was 2 weeks. In rat liver the activity of quinone reductase (QR), heme oxygenase-1 (HO-1), paraoxonase-1 (PON-1), glutathione-S-transferase (GST), ethoxyresorufin-O-dealkylase (EROD) activity of CYP1A1, methoxyresorufin-O-dealkylase (MROD) activity of CYP1A2, tes- tosterone 6ß-hydroxylase (6ß-TG) activity of CYP3A, total antioxidant activity (AOA) and malondialdehyde (MDA) content have been investigated. The expression of genes CYP1A1, CYP1A2 and CYP3A has been measured by reverse transcription-polymerase chain reaction (RT-PCR). The stability of lysosome membranes was estimated by the change of unsedimentable activity of lysosomal enzymes--arylsulfatase, ß-galactosidase and ß-glucuronidase. Rutin administration led to dose-dependent increase in the activity of antioxidant enzymes. In rats of the 3rd group received high-rutin diet the activity of QR, HO-1, PON-1 and GST increased by 68, 29, 17 and 22%, respectively, compared to the control (1st group); MDA level and AOA have not changed. Activity of EROD and MROD in liver microsomes of rats treated with rutin at a dose of 40 mg/kg b.w. (2nd group) increased by 33 and 58%, respectively, with a moderate increase in mRNA level of CYP1A1 and CYP1A2. Increasing the dose of rutin up to 400 mg/kg b.w. (3rd group) resulted in the decrease of the degree of EROD and MROD activation by 18 and 15%, respectively, compared to the 2nd group. Rutin had no significant effect on the activity of 6ß-TG and on the expression of CYP3A1 gene. Rutin dietary administration led to dose-dependent reduction of the unsedimentable activity of lysosomal enzymes, indicating the strengthening of the stability of lysosomal membranes. Thus, the obtained results showed that in healthy, intact rats high doses of rutin in the diet moderately but statistically significantly activate enzyme systems responsible for the protective and adaptive capacity of the organism.

[Effects of omega-3 polyunsaturated fatty acids on antioxidant capacity in rats].

Dietary administration of omega-3 polyunsaturated fatty acids (EPA + DHA, 1,2:1) at dose 0.3 or 1 g/kg bw during 4 weeks led to minor (by 14% and 17%, p<0.05) decrease of serum antioxidant capacity and serum level of vitamin E (by 30% and 31%, p<0.05) and the activity of paraoxonase-1 (by 14% at 0.3 g/kg bw, p<0.05). The activity of antioxidant enzymes in liver increased in a dose-dependent manner. At higher dose of omega-3 polyunsaturated fatty acids a 45% increase in the activity of paraoxonase-1 (p<0.05), 21% -heme oxygenase-1 (p>0.05), 68% - quinone reductase (p<0.05), 19% - glutathione S-transferase (p<0.05) compared to the control group was found. The direct relationship between activities of enzymes and increase of MDA level in liver (by 47 and 107%, p

[Effects of dietary fat level on the xenobiotic metabolism enzymes activity and antioxidant enzymes in rats].

Male Wistar rats received fat-free diet or diets containing 5, 10 and 30% of fat (sunflower oil + lard, 1:1) for 4 weeks. The direct relationship between dietary fat level and ethoxyresorufin O-dealkylase activity of CYP1A1, methoxyresorufin O-dealkylase activity of CYP1A2, pentoxyresorufin O-dealkylase activity of CYP2B1 and testosterone 6beta-hydroxylase activity of CYP3A was found. Activities of key enzymes of phase II xenobiotic metabolism (total activity of glutathione transferase, activity of UDP-glucuronosyle transferase) and antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, paraoxonase-1 and heme oxygenase-1) also increased with higher dietary fat level.

[Effects of green tea extract and its components on antioxidant status and activities of xenobiotic metabolizing enzymes of rats].

Dietary administration of green tea extract (GTE) or epigallocatechin gallate (EGCG), quercetin (Qu) or caffeine (Cf) in doses equal to their concentration in GTE led to an increase of serum and liver antioxidant capacity and strengthening stability of microsomal and lysosomal membranes in rats. The antioxidant efficiency of EGCG and Qu was considerably higher than that of GTE. There were significant differences in the effects of EGCG, Qu and GTE on the activities and expression of mRNA for CYP1A1, CYP1A2 and CYP3A1. But feeding both GTE and Cf to rats results in similar elevated activities of CYP1A1, CYP1A2, UDP-glucuronosyl transferase and glutathion transferase. Our results suggest that Cf is the main contributor to GTE effects on activities of xenobiotic metabolizing enzymes.

Effects of combined treatment with resveratrol and indole-3-carbinol.

Male Wistar rats received a semisynthetic diet with resveratrol (100 mg/kg), indole-3-carbinol (20 mg/kg), or a mixture of these compounds in the same doses for 1 week. Activities of ethoxyresorufin dealkylase (EROD), methoxyresorufin dealkylase (MROD), pentoxyresorufin dealkylase (PROD), and 6ß-testosterone hydroxylase (6ß-TH) and the content of mRNA for CYP1A1, CYP1A2, and CYP3A1 were elevated in the liver of rats receiving indole-3-carbinol. These changes were accompanied by an increase in activity of phase II xenobiotic metabolism enzymes (quinone reductase, hemoxygenase-1, glutathione transferase, and UDP glucuronosyl transferase). Resveratrol did not modify activity of these enzymes. After combined treatment with the test compounds, resveratrol suppressed the indole-3-carbinol-induced increase in activities of EROD, MROD, PROD, and 6ß-TH, and expression of the corresponding genes. Combined treatment was characterized by potentiation of the antioxidant effects of these compounds.

[Effect of soybean isoflavones on antioxidant status in rats fed diet with oxidized linseed oil]. / Vliianie izoflavonov soi na antioksidantnyi status krys, poluchavshikh ratsion s okislennym l'nianym maslom.

The maintenance of male Wistar rats on semi-synthetic diets containing oxidized flaxseed oil for 4 weeks caused decrease in serum total antioxidant activity, significant suppression of microsomal UDP-glucuronosyl transferase activity and benzpyrene hydroxylase activity, increase in reduced glutathione level and catalase activity of liver. Supplementation of diets with 0.05% of soy isoflavones has resulted in normalization of investigated characteristics.

[Medical-biological evaluation of genetically-modified sugar beet line 77 (chemical composition and toxicologico-biochemical studies)]. / Mediko-biologicheskia otsenka geneticheski modifitsirovannoi sakharnoi svekly linii 77 (khimicheskii sostav i toksikologo-biokhimicheskie issledovaniia).

The rats were fed with the Genetically Modified Sugar Beet line 77 (Monsanto Ko, USA) 10 g/rat/day for 1 month. Their blood, urea and liver were investigated to measure total protein and glucose levels, aminotransferase and alkaline phosphatase activities, pH, creatinine level as well as hepatic enzyme activity of the I and II phases of xenobiotic metabolism and whole and non-sedimentated lysosomal enzyme activities and activity of antioxidant system.

[Medico-genetic evaluation of sugar sand, obtained from genetically-modified sugar beet line 77 (toxicologico-biochemical studies)]. / Mediko-biologicheskaia otsenka sakhara-peska, poluchennogo iz geneticheski modifitsirovannoi sakharnoi svekly linii 77 (toksikologo-biokhimicheskie issledovaniia).

The rats were fed with the Suger from the Genetically Modified Suger Beet line 77 (Monsanto Ko, USA) 3 g/rat/day for 3 months. Their blood, urea and liver were investigated to measure total protein and glucose levels, aminotransferase and alkaline phosphatase activities, pH, creatinine level as well as hepatic enzyme activity of the I and II phases of henobiotic metabolism and whole and non-sedimentated lysosomal enzyme activities and activity of antioxidant system.

[Protective influence of bioactive food supplement "Rekicen RD" in alimentary T-2-mycotoxicosis in rats]. / Zashchitnoe deistvie BAD "Rekitsen-RD" pri alimentarnom T-2-mikotoksikoze y krys.

Inclusion of a biologically active food supplement (BAS) "Rekicen RD" in rat Wistar ration in percentage 5% result in reduction of toxic action of a trichothecene mycotoxin T-2 toxin. The changes of daily increase in body weight of animals, of relative internal weight, of serum enzyme activity, of not sedimentated activity of lysosomal enzymes and of activity of enzymes of a xenobiotic metabolism in a liver were expressed in a lesser degree. It is possible that a protective action of BAS is related with high adsorption capacity of wheat bran in BAS composition and with their possible influence on activity of enzymes participating in detoxification T-2 toxin (UDP-glucuronosyltransferase).

[Effect of dietary selenium on the activity of UDP-glucuronosyltransferases and metabolism of mycotoxin deoxynivalenol in rats]. / Vliianie urovnia selena v ratsione na aktivnost' UDP-gliukuronoziltransferaz i metabolizm mikotoksina dezoksinivalenola u krys.

The influence of selenium excess and deficiency on the activity of xenobiotic metabolizing enzymes and the metabolism of mycotoxin deoxynivalenol (DON) in rats was studied. Wistar male rats were fed for 6 weeks semi-synthetic diets containing 0.2, 1.0 or 5.0 ppm selenium. For induction of selenium deficiency the weanling rats were fed for 6 weeks diet containing < or = 0.02 ppm selenium. The activity of selenium-dependent glutathione peroxidase was reduced in the liver of selenium-deficient rats by 93% at 42 days. DON, its de-epoxy metabolite DOM-1, DON and DOM-1 glucuronides were analyzed by reverse-phase HPLC in urine and feces after the single oral dose of DON (8 mg/kg). Selenium-supplemented (5 ppm) diet increased by 2-3 times formation and elimination of DON and DOM-1 glucuronides in urine. Selenium-deficient diet decreased formation of DOM-1, but increased significantly total excretion of DON and DON glucuronides. The activity of GT1 and GT2 forms of UDP-glucuronosyltransferase, an enzyme principally responsible for glucuronidation, was two times higher in the liver of rats fed both selenium-supplemented and selenium-deficient diets.

[Xenobiotic-metabolizing enzymes in rat liver and small intestinal mucosa with varying combinations of polyunsaturated omega-6 and omega-3 fatty acids in the diet]. / Fermenty metabolizma ksenobiotikov pecheni i slizistoi obolochki tonkoi kishki drys pri razlichnykh sochetaniiakh polinenasyshchennykh zhirnykh kislot omega 6 i omega 3 v ratsione.

Male Wistar rats were fed for 30 days semi-synthetic diets containing lard, corn oil or fish oil (ichthynic oil from herring muscles), differing in total content of saturated and polyunsaturated fatty acids (PUFA), in the ratio omega 6/omega 3 PUFA and in content of vitamin E. The activity of xenobiotic metabolizing enzymes was similar in liver of rats fed diets with lard or corn oil, while activities of epoxide hydrolase and UDP-glucuronosyltransferase were significantly higher if fish oil was used. The type of fat affected also the benzyl-produced induction of the enzymes. Differences in the enzyme activities observed did not depend on content of vitamin E in dietary fats. Unlike liver tissue, activities of microsomal enzymes were not considerably altered in rat small intestine in various experimental groups. The microsomal lipids of liver tissue and small intestine mucosal membrane were similar in the total content of saturated and unsaturated fatty acids in various animal groups but the level of omega 6 and omega 3 PUFA in the tissues depended on the ratio omega 6/omega 3 PUFA in diets.

[The effect of selenium on enzymes metabolizing xenobiotics in rat liver]. / Vliianie selena na fermenty metabolizma ksenobiotikov pecheni krys.

Activity of enzymes involved in metabolism of xenobiotics was not altered in liver tissue of rats kept on a ration enriched with selenium at a dose of 2.5 mg/kg. Both organic form of selenium (yeast meal, selenomethionine) and inorganic derivatives (sodium selenite) at a dose of 5 mg/kg of ration caused distinct activation of epoxide hydrolase, UDP-glucuronosyl transferase and glutathione transferase within 6 weeks after the experiment beginning, while content of cytochrome P-450, glutathione-SH and glutathione peroxidase activity were not significantly altered. Within 9 weeks the enzymatic activity remained at the higher rate only in rats kept on the ration with sodium selenite. Relationship between toxic effects of selenium high doses and alterations in activity of enzymes involved in metabolism of xenobiotics is discussed.

[Protective effect of selenium in acute T-2 mycotoxicosis]. / Zashchitnoe deistvie selena pri ostrom T-2-mikotoksikoze.

Male Wistar rats were fed diets supplemented with selenium (0.5 and 2.5 mg/kg) for 6 weeks. When T-2 toxin was administered at 3.8 mg/kg body weight; sings of intoxication were less distinct in rats fed selenium-supplemented diets. Mortality caused by T-2 toxin was two times lower if selenium content amounted to 2.5 mg/kg. The level of cytochrome P-450 and the rate of deethylation of 7-ethoxycoumarin were considerably decreased in the liver of rats that received T-2 toxin and fed a diet with high selenium content. At the same time the activity of epoxide hydrolase and UDP-glucuronosyltransferase was significantly higher (1.6 and 1.7 times more) as compared with unsupplemented group. The results obtained allow to assume that there is a relationship between the decrease of T-2 toxin toxicity and the change in its metabolism in rats fed selenium-supplemented diets.