1. The O-dealkylation of seven 7-alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7-alkoxyquinoline metabolism was studied. 2. None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3. Maternal cigarette smoking induced the O-dealkylation of all of the 7-alkoxyquinoline derivatives, being greatest for 7-butoxy- and 7-benzyloxyquinoline. 4. Placental 7-alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1-7-1 raised against 3-methylcholanthrene-induced rat liver P450. 5. None of the 7-alkoxyquinoline O-dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta.
The promoter sequence variant -480T in the hepatic lipase gene (LIPC) has been shown to be significantly associated with low post-heparin hepatic lipase activity. Some studies have also found that the -480T variant is associated with elevation in plasma HDL cholesterol. We tested for associations of LIPC -480T with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 657 Alberta Hutterites, 328 Ontario Oji-Cree and 210 Keewatin Inuit. Plasma HL activity was not available for analyses. The LIPC -480T allele frequencies in these three groups, respectively, were 0.219, 0.527 and 0.383, and the prevalence of LIPC -480T/T homozygotes was, respectively, 0.042, 0.274 and 0.167. No significant association was found between LIPC -480T and plasma HDL cholesterol or apolipoprotein AI concentration, after adjusting for covariates including gender and body mass index. There was no consistent relationship between the population mean plasma HDL cholesterol concentration and the population LIPC -480T frequency. Our findings are consistent with the idea that the common promoter variation in LIPC, which has been reported to be associated with variation in post heparin HL activity and HDL triglyceride concentration, is not always associated with variation in plasma HDL cholesterol concentration, possibly due to yet unspecified environmental or genetic factors.
The influence of 0.01% sodium dodecyl sulphate, 1.5 and 6.0 M urea and 0.03 M hydrogen peroxide to the NAD(P)H: 2,6 dichlorphenolindophenol reductase activity in livers of adult and old Wistar rats during immobilizing stress was interested. Obtained results indicate that the NADPH--dependent reductase is more resistant to modulating effect of sodium dodecyl sulphate, hydrogen peroxide and urea than NADH-dependent enzyme. The significant decrease of NADH: 2.6 dichlorphenolindophenol reductase sensitivity to the action of all studied modulators occurs in old rats. The similar changes appears in the adult rats liver during stress. The old rats immobilization is accompanied by a decrease of this enzyme activity and the reduction of the influence of all studied modulators to NADH: 2.6 dichlorphenolindophenol reductase as compared with adult ones. These changes in the activity and properties of microsomal NADH: 2,6 dichlorphenolindophenol reductase promote more pronounced decrease of the substrate hydroxylation in the liver of old rats during stress compared to adult ones.
We measured activity and content of cathepsin B in tumor tissues, liver, and spleen in mice with Lewis adenocarcinoma and LS-lymphosarcoma. Cathepsin B activity in Lewis adenocarcinoma cells was lower than in LS-lymphosarcoma cells, which was probably related to differences in their metastatic properties. Antitumor therapy increased activity and content of cathepsin B in tumor tissues. Changes in the content and activity of cathepsin B in tumor tissues can serve as a prognostic criterion for tumor regression during therapy. Cathepsin B is probably involved in apoptosis of tumor cells during chemotherapy of lymphosarcoma-LS with cyclophosphamide.
11beta-Hydroxysteroid dehydrogenase activity in the kidneys of NISAG rats (rat strain with hereditary stress-induced arterial hypertension) was 1.5-fold higher than in WAG rats. An inverse relationship was observed in the liver of these animals. After stress exposure 11beta-hydroxysteroid dehydrogenase activity remained unchanged in the kidneys of NISAG and WAG rats, but significantly increased in the liver of NISAG rats. Functional activity of 11beta-hydroxysteroid dehydrogenase probably reflects the hypertensive state of NISAG rats.
The dynamics of the acid and neutral proteinases general enzymes activity change in the hepatocytes postnuclear fraction in the rats suffering from the Heren's carcinoma was investigated. It was determined that in the tumor development of the enzyme activity level of both the acid and neutral proteinases increased 2,6-fold. The natural preparation of the herbs (Calendula officinalis L., Echinacea purpurea L., Scorzonera humilis L., Aconitum moldavicum Hacq.) normalizes both the activity of the investigated enzymes and coefficients of the liver weights of the sick animals. The chemical medicinal preparation 5,6-benzcumarine-5-uracil normalizes the activity of the neutral cytoplasmatic proteinases and reduces the level of the proteolytic activity of the acid enzymes in comparison with the control group of the animals as well as increases of the liver weight coefficients.
The state of enzymatic antioxidant system and thyroid status in the rat tissues under early postnatal overnutrition leading to shortening of life-span and calorie-restricted diet extending lifespan have been studied. It was found that the concentration of thyroxine, body weight and content of lipid hydroperoxides in the blood serum and liver post-mitochondrial fraction of rats had been reliably increased. At the same time the concentration of GSH and GSSG, superoxide dismutase, Se-dependent glutathione peroxidase (GP) activities in the liver and GP activity in the blood serum of experimental rats were reduced. The use of calorie-restricted diet for 2 months showed considerable decrease of thyroxine and triiodothyronine concentration, body weight and the content of lipid hydroperoxides in the blood serum of experimental rats compared with control. At the same time GP activity in the liver, Se-dependent GP activity and content of ceruloplasmin in blood of experimental rats were essentially enhanced. The obtained results allow to conclude that from all studied indices the activity of GSH-dependent antioxidant system (especially Se-dependent GP activity) and thyroid status revealed the most sensible changes in response to the used kind of nutrition. Unlike hypocaloric diet overnutrition results in a decrease of Se-dependent GP activity in the liver and blood of rats. That may be the most crucial moment in the maintenance of prooxidant-antioxidant balance of tissues.
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.
The developmental dynamics of pathologic changes in the lenses and activity of glutathione-S-transferase in the blood plasma, liver and lens tissues of rabbits under chronic influence (2 months) of small doses of X-ray radiation (total dose 2 Gy) and polychromatic light have been researched. It was shown, that polychromatic light and X-ray irradiation of rabbits significantly affected the lens nativity and increased the developmental frequency and the intensity of lens opacities. It was determined, that activity of glutathione-S-transferase in blood plasma increased for 1 month after the beginning of X-ray effects. The same effect on the enzymatic activity was shown by the summary influence of polychromatic light and X-ray irradiation. Glutathione-S-transferase activity decreased during 2 months as compared with the initial values, before irradiation of the animals. The enzymatic activity was increased in rabbit-liver cytoplasm by X-ray irradiation in 2 months. A decrease of glutathione-S-transferase activity in the liver, cortex and lens nucleus was determined under the influence of both X-ray radiation and polychromatic light.