[Changes in proteome profiles of rat liver microsomes induced by silicon dioxide nanoparticles].

The effect of daily intragastric administration of an aqueous dispersion of silicon nanoparticles (NPs) (the dose range from 1.0 mg/kg to 100 mg/kg body weight for 28 days) to rats on the proteomic profile of liver microsomes has been investigated by 2D-electrophoresis followed by subsequent mass spectrometry identification. The liver microsomal fraction was isolated by differential centrifugation and its protein composition was analyzed by 2D-polyacrylamide gel electrophoresis. Identification of protein spots was carried out using MALDI-TOF mass spectrometric analysis. The mass spectrometry analysis revealed the protein GRP78 (78 kD glucose-regulated protein precursor), belonging to the family of heat shock proteins. This protein present in animals of the control group was not detected in NP-treated rats of group 2 (1 mg/kg body weight/day) and group 3 (10 mg/kg body weight/day). This protein predominantly localized in the liver cell endoplasmic reticulum and plasma membrane has the chaperone biological activity. Possible mechanisms of the effects of engineered nanoparticles on biosynthetic processes in the body are discussed.

Effect of polyunsaturated fatty acids ω-3 on the induction of activity and expression of CYP1A1 and CYP1A2 genes in the liver of rats under the influence of indole-3-carbinol.

Supplementation of the ration with eicosapentaenoic and docosahexaenoic ω-3 polyunsaturated fatty acids (PUFA) in doses of 0.3 and 1 g/kg body weight for 4 weeks had no effect on ethoxyresorufin O-dealkylase (EROD) activity and expression of the CYP1A1 gene in male Wistar rats, but caused a dose-dependent increase in methoxyresorufin O-dealkylase (MROD) activity of CYP1A2 (by 28 and 73%, respectively) without significant changes in CYP1A2 mRNA expression. ω-3 PUFA had no effect on the indole-3-carbinol-induced (20 mg/kg body weight over the last 7 days of the experiment) EROD activity and expression of CYP1A1 mRNA. The indole-3-carbinol-induced MROD activity was shown to increase by 6.2 times in rats not receiving ω-3 PUFA and only by 3.9 and 2.7 times in animals receiving ω-3 PUFA. The indole-3-carbinol-induced expression of CYP1A2 mRNA slightly increased in animals receiving ω-3 PUFA. Our results suggest that the effect of ω-3 PUFA on the induced and basal activity of CYP1A2 is not related to modulation of CYP1A2 gene expression.

Effect of lycopine on the resistance of rat liver microsomes to in vitro induced LPO.

Lycopine in concentrations of 0.5-50 microM suppressed LPO in microsomes induced by NADPH-Fe(2+) and by ascorbic acid-Fe(2+). Lycopine in a concentration of 20 microM completely prevented the decrease in the rate of benz[a]pyrene hydroxylation and activation of p-nitrophenyl-UDP-glucuronosyl transferase caused by LPO induction in microsomes.

Antioxidant status of rats receiving lycopene in different doses.

Oral treatment with lycopene (per os) in doses of 10 or 50 mg/kg for 2 weeks led to accumulation of lycopene in the liver, liver microsomes, and blood plasma, increased total plasma antioxidant activity, inhibited LPO in the liver, and decreased solubilization of lysosomal enzymes. Lycopene had no effect on ex vivo resistance of liver microsomes to LPO and activities of antioxidant enzymes in the liver.

Physiological role of short peptides in nutrition.

Here we review new data about the physiological role of short peptides and their use as biologically active food additives (parapharmaceutics). Some approaches to the development of peptide preparations for peroral administration are considered and the mechanisms of nonspecific and tissue-specific effects produced by peroral peptide parapharmaceutics are discussed. Particular attention is given to biological properties of short peptides synthesized at the St. Petersburg Institute of Bioregulation and Gerontology. These peptides hold much promise for the synthesis of parapharmaceutics increasing organism's resistance to extreme factors and preventing accelerated aging and age-related diseases.

Flavonoids and resveratrol as regulators of Ah-receptor activity: protection from dioxin toxicity.

In 2002 FAO and WHO published a joint appeal to state and public organizations and scientific community to take every effort to control the contents of dioxin and related biphenyls in the environment and food products. The toxic effects of dioxin are realized via its interaction with the Ah-receptor. Here we reviewed modern notions about the structure and functions of Ah-receptor. Particular attention was given to antagonists and agonists of the Ah-receptor, including various flavonoids and resveratrol.

Effects of flavonoids on the resistance of microsomes to lipid peroxidation in vitro and ex vivo.

Incubation of rat liver microsomes with preparations of grape flavonoids, dihydroquercetin, and silibinin increased their resistance to lipid peroxidation induced by NADPH-Fe2+. This was manifested in less pronounced accumulation of lipid peroxidation products and changes in activity of microsomal enzymes induced by lipid peroxidation. In vitro antioxidant activity of grape flavonoids markedly surpassed that of dihydroquercetin and silibinin. Addition of flavonoids into fodder led to moderate, statistically significant, and similar increase in the resistance of rat liver microsomes to ex vivo induced lipid peroxidation.

Effect of nutritional indoles on activity of xenobiotic metabolism enzymes and T-2 toxicity in rats.

Experiments on Wistar rats showed that feeding a ration containing 0.1% concentrate of food indoles (indole-3-carbinole and ascorbigen) for 3 weeks increased activity of phases I and II xenobiotic metabolism enzymes in the liver and intestinal mucosa and weakened the toxic effects of trichothecene T-2 mycotoxin. Activity of the key enzymes of T-2 detoxification, microsomal carboxylesterase and UDP-glucuronosyl transferase, was 1.5-2-fold higher in rats receiving T-2 toxin against the background of indole-enriched diet compared to toxin-treated rats kept on standard ration.

[Determination of lysosome membrane stability].

Effect of different concentration of non-ionic detergents (Triton X-100, Triton X-305, BRIJ-35 and Triton WR-1339) on total and non-sedimentable activity of 8 rat liver lysosome enzymes (acid phosphatase, acid DNase, acid RNase, arylsulphatases A and B, beta-glucuronidase, beta-galactosidase, beta-glucosidase and beta-acetylglucosaminidase) was studied. Only Triton X-100 at the concentration of 0.1% (and higher) was found to release completely lysosome enzymes. Low concentrations of Triton X-100 (0.025-0.05%) were used to characterize the strength of enzyme binding: the level of releasing acid DNase, beta-galactosidase, beta-glucuronidase and acid phsophatase being considerably higher than that of other lysosome enzymes studied. On the basis of the data obtained a method is worked out, which is suitable for series studies of the stability of lysosome membranes under different physiological and pathological conditions. The essence of the method is the treatment of membrane particles with increasing concentrations of Triton X-100 (0.025; 0.05 AND 0.1%) AND THE SUCCESSIVE ESTIMATION OF NON-Sedimentable activity of marker enzymes. The method detected troubles in the stability of rat liver lysosome membranes under starvation, protein deficiency and aging.

Action of the mycotoxin of Fusarium sporotrichiella v. sporotrichioides on lysosomal membranes.

The effect of the mycotoxin of Fusarium sporotrichiella v. sporotrichioides (sporofusarin) was studied in vitro on the total and nonsedimenting activity of eight lysosomal enzymes: acid ribonuclease, aryl sulfatases A and B, beta-glucuronidase, alpha- and beta-galactosidases, beta-glucosidase, beta-acetylglucosaminidase, and alpha-mannosidase. Incubation of a suspension of rat liver lysosomes with an aqueous solution of sporofusarin led to inhibition of the total activity of the membrane-bound lysosomal enzyme beta-glucosidase. In a dose of only 1.6 x 10-5 M sporofusarin caused a significant increase in the nonsedimenting activity of nearly all the enzymes; in a concentration of 1.6 x 10-3 M most of the enzymes of the lysosomal matrix (beta-glucuronidase, beta-galactosidase, aryl sulfatases A and B) were liberated almost completely into the supernatant, and nearly all the beta-glucosidase also was liberated. It is postulated that damage to the subcellular membranes is an important component of the toxic action of sporofusarin.