Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats.

We investigated the effects of silymarin and naringenin in counteracting arsenic-induced hepatic oxidative stress post exposure. Male wistar rats were chronically exposed to sodium arsenite for eight months followed by oral treatment with silymarin and naringenin (50 mg/kg each) for 15 consecutive days to evaluate hepatic damage and antioxidant potential. Our results demonstrate a significant decrease in hepatic GSH levels, SOD and catalase activities and an increase in GST and TBARS levels after arsenic administration. Silymarin or naringenin administration increased GSH levels and was beneficial in the recovery of altered SOD and catalase activity besides significantly reducing blood and tissue arsenic concentration. Our results point to the antioxidant potential of these flavonoids, which might be of benefit in the clinical recovery of subject exposed to arsenic. These flavonoids can be incorporated into the diet or co-supplemented during chelation treatment, and thus may afford a protective effect against arsenite-induced cytotoxicity.

[The effect of 2,4-dinitrophenol on the intensity of oxidative processes in the rat liver during prolonged experiment].

The effect of uncoupler 2,4-dinitrophenol on the oxidative processes intensity in liver biomembranes of different age and sex of rats during longitudinal experiment was studied. It was established that 2,4-dinitrophenol in the used concentration hadn't essential negative effect on the organism of females and their posterity. On the young, 3-3,5-month old males it was shown that long-term xenobiotic administration had been accompanied by intensification of the rate of oxygen consumption, decrease of the rate of reactive oxygen species formation in microsomal redox-chain, decline in lipid hydroperoxides and protein carbonils levels in blood serum and liver microsomes, and also by increase of their mean lifespan. The obtained results may testify the possibility of correction of oxidative processes intensity in tissues of mammals and their lifespan by means of modulation of membrane electron transport chains activity.

[The protein oxidative damage level and lifespan modulation by xenobiotics in Drosophila melanogaster].

The effect of xenobiotics on protein oxidative damage and lifespan of Drosophila melanogaster Meig., line Oregon-R, was studied. Addition of the uncoupler 2,4-dinitrophenol (DNP) to the nutritional mixture results in an induction of synthesis of heat shock proteins and increase of lifespan of insects, whereas sodium nitroprusside (SNP) has negative effect on flies viability connected, probably, with activation of processes of proteins oxidative damage. It is shown that DNP essentially corrects the SNP negative action on insects' survival rates and this "normalizing" action is revealed both at a level of sensitivity of flies to exogenic stresses and protein carbonils level and at a level of insects lifespan as a whole. It is supposed that DNP protects from SNP negative action on flies viability by reduction of intensity of free radicals production and/or induction of heat shock proteins synthesis. Consequence of that is reduction of oxidative proteins damage degree and increase of survival rate (life span) of flies.

[The influence of gamma-irradiation and alimentry factors on prooxidant-antioxidant rat's liver and blood system].

The shift of prooxidant-antioxidant balance in side of prooxidants was revealed in rat liver mitochondria and in microsomes and in blood plasma in response to single irradiation (dose 8 Gy). The shift was more expressed in animals with nutrition unbalanced on animal proteins and antioxidant vitamins. In the main it was explained by the initially reduced activity of enzymatic antioxidant system and especially Se-dependent glutathione peroxidase activity. The apply of food addition from Aronia melanocarpa fruits had delayed lipid peroxidation activation in irradiated animals but practically had no effect on activity of enzymatic antioxidant system. The established essential decrease of Se-dependent glutathione peroxidase activity under unbalanced diet is considered the most crucial point in the maintenance of enzymatic antioxidant system reliability in irradiated animals.

[Activity of glutathione-dependent antioxidant system of the rat liver and blood depending on gamma-irradiation and diet].

The role of the glutathione-dependent antioxidant system in the prooxidant-antioxidant balance support was studied in the experiments with Wistar male rat under single gamma-irradiation (8 Gr dose), fed with unbalanced (as to animal proteins and antioxidant vitamins) diet and with addition of Aronia melanocarpa. Single gamma-irradiation of animals led to the decrease of selenium-dependent glutathione-peroxidase activity in the blood plasma and glutathione-S-transferase activity decrease in rat liver mitochondria. Animals which received the unbalanced food allowance under irradiation showed more expressed change of glutathione-dependent antioxidant enzymes activity, namely--proved decrease of glutathione-peroxidase and glutathione-S-transferase activity in liver microsomes and less expressed activation of selenium-dependent glutathione-peroxidase activity in the postmitochondrial fraction of laboratory animals liver. Introduction of the A. melanocarpa food supplement in the unbalanced diet of the laboratory animals which in vitro demonstrated expressed antioxidant and antiradical activity had no effect upon glutathione-peroxidase activity in the investigated tissues. Obtained data concerning significant decrease of the activity of glutathione-dependent antioxidant system and, particularly, of the selenium-dependent glutathione-peroxidase activity under the unbalanced diet condition may be useful in maintenance of prooxidant-antioxidant balance in the tissues of irradiated animals. Allowing for the above stated it is advisable to seek for new food additives which increase activity of the endogenous glutathione-dependent antioxidant enzymes for human tolerance improvement, especially under the unbalanced food allowance condition.

Uncoupler of oxidative phosphorylation prolongs the lifespan of Drosophila.

The effect of a moderate ("soft") uncoupling of mitochondria on the lifespan and some parameters of biological age of Drosophila melanogaster strain Oregon was studied. Addition of the uncoupler 2,4-dinitrophenol (DNP) to the nutritional mixture of larvae significantly increased the average lifespan of the flies without changing their maximal lifespan. DNP significantly increased the rate of oxygen consumption by isolated mitochondria and tissue homogenates of the flies in state 4 (of Chance). DNP also decreased the activity of alcohol dehydrogenase (a parameter of flies' biological age) in the tissue homogenates, especially on octanol as the reaction substrate. However, being deprived of food the DNP-treated flies displayed a markedly decreased viability as compared to the control flies. On the whole, the results suggest that "soft" uncoupling of mitochondria may increase the lifespan.

[Effect of caloric restricted diet on the liver microsomal monooxygenase system in rats of various ages]. / Vliianie kaloriino ogranichennoi diety na mikrosomnuiu monooksigenaznuiu sistemu pecheni krys raznogo vozrasta.

Dietary restriction is the only known experimental method to extend lifespan in mammals, but the mechanisms of this phenomenon are still unknown. It is determined that the keeping of animals on the calorie restricted diet results in essential changes of a drug-metabolizing enzymes contents, that is also confirmed by the change of response of the enzyme system to thyroxine action. As a whole, the results obtained will be coordinated with the point of view, according to which the action mechanisms of the dietary restriction consist in considerable change of a wide spectrum of biochemical processes, including the change of the level of monooxygenase system functioning.

Age-dependent changes in rat liver microsomal membrane structure and functions under benzene treatment.

The influence of benzene on 3 and 24 months old rat liver microsomes was studied. Some structural and functional changes occur under benzene treatment in the cytochrome P-450 system which are more pronounced in 3 months old rat microsomes than in the 24 months ones. Glucose-6-phosphatase and glucose dehydrogenase activities indicate that 3 months old rat microsomal vesicles are more stable against benzene injury than those, of 24 months old ones. In vitro benzene hydroxylation activation by NADPH addition decreased disruptive xenobiotic's effect on 3 but not on 24 months old rat liver microsomal vesicles. This fact suggests that the rate of benzene hydroxylation is important for its membrane damaging action effect. Thus, age-related differences in xenobiotic action on liver microsomes could be related to the decrease of benzene metabolism rate with senescence.

[Effect of paracetamol on the microsomal oxidation, oxidative phosphorylation and liver mitochondria swelling in rats of various ages]. / Vliianie paratsetamola na mikrosomal'noe okislenie, okislitel'noe fosforilirovanie i nabukhanie mitokhondrii pecheni krys raznogo vozrasta.

The effect of hepatotoxic dose of paracetamol (800 mg per kg, intraperitoneally, once a day during two days) on the system of microsomal oxidation, respiration, oxidative phosphorylation and high amplitude swelling of liver mitochondria was studied on 1-, 4- and 30-months old Wistar male rats. It has been shown, that paracetamol injection leads to the decrease of content of cytochrome P-450, to disorders of the function of monooxygenase system (the aminopyrine-N-demethylase and aniline hydroxylase activities were diminished), mitochondria macrostructure (the mitochondria high amplitude swelling time was decreased) and function (the respiratory control was decreased). These alterations have been observed to manifest to more extent in the liver of young rats as compared with old ones.

[Activity of key enzymes of heme synthesis and degradation and contents of cytochromes b5 and P-450 in rat liver]. / Aktivnost' kliuchevykh fermentov sinteza i raspada gema i soderzhanie tsitokhromov b5 i P-450 pecheni krys.

The relation between the delta-aminolevulinate-synthase and heme-oxygenase activities and the contents of cytochromes b5 and P-450 in rat liver after phenobarbital and CoCl2 injections was studied. Two hours after a single injection of phenobarbital the delta-aminolevulinate-synthase activity is increased, showing a further rise after 24 hrs. The content of cytochrome b5 is not changed, while that of cytochrome P-450 is increased 24 hrs after the injection. The heme-oxygenase activity remains unaffected thereby. The increase in the enzyme activity and cytochrome P-450 content induced by phenobarbital is eliminated by a preliminary administration of actinomycin D. The administration of CoCl2 is accompanied by a decrease in the delta-aminolevulinate-synthase activity after 2 hrs and its further increase after 24 hrs. The heme-oxygenase activity shows a sharp rise 24 hrs after the injection. The rise in the delta-aminolevulinate-synthase activity induced by CoCl2 is removed by actinomycin D. CoCl2 decreases the content of cytochromes b5 and P-450 24 hrs after the injection. It is assumed that the correlation between the delta-aminolevulinate-synthase activity and cytochrome P-450 content is observed only in the case when the heme-oxygenase activity is not increased. The cytochrome b5 content is independent of the changes in the activity of the key enzyme of heme synthesis and depends to a certain extent on the rate of heme degradation by heme-oxygenase.