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1

Paraoxonase 1 and dietary hyperhomocysteinemia modulate the expression of mouse proteins involved in liver homeostasis

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Suszynska-Zajczyk J., Jakubowski H.
Acta Biochimica Polonica
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2014
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tom 61
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nr 4
2
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The effect of peroxisome proliferator-activated receptors alpha (PPARalpha) agonist, fenofibrate, on lipid peroxidation, total antioxidant capacity, and plasma paraoxonase 1 (PON1) activity

100%
Beltowski J., Wojcicka G., Mydlarczyk M., Jamroz A.
Journal of Physiology and Pharmacology
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2002
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tom 53
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nr 3
The aim of this study was to investigate the effect of peroxisome proliferator activated receptors alpha agonist, fenofibrate, on the level of oxidative stress, total antioxidant capacity, and plasma paraoxonase 1 (PON1) activity in the rat. The adult male Wistar rats received fenofibrate for 7 days. The drug was added to food at concentrations 0.005%, 0.05% and 0.5%, which corresponded to doses of 3, 30 and 300 mg/kg/day, respectively. Fenofibrate treatment dose-dependently reduced plasma concentration of malonyldialdehyde and 4-hydroxydialkenals. The level of these lipid peroxidation products in animals treated with 0.005%, 0.05% and 0.5% fenofibrate was lower than in control group by 52.8%, 62.7% and 87.1%, respectively. Lipid hydroperoxides in plasma decreased by 29.7%, 23.4% and 27.5% in these groups, respectively. The drug had no significant effect on total antioxidant capacity measured as ferric reducing ability of plasma (FRAP). Paraoxon-hydrolyzing activity (PON) of plasma paraoxonase was 81.5% lower in animals receiving 0.05% fenofibrate and 69.2% lower in rats treated with 0.5% fenofibrate than in control. Phenyl acetate hydrolyzing activity (arylesterase, AE) was reduced by 15.2%, 49.6% and 55.8% in rats receiving 0.005%, 0.05% and 0.5% fenofibrate, respectively. PON/AE ratio decreased following 0.05% and 0.5% fenofibrate by 64.9% and 30.4%, respectively. The drug had no significant effect on total plasma triglycerides and cholesterol concentrations. The results indicate that fenofibrate treatment favourably modulates oxidant-antioxidant balance and unfavourably affects plasma PON1 activity in normolipidemic rats. These effects can contribute to the influence of PPARalpha agonists on pathological processes involved in atherogenesis.
3
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Effect of quercetin on paraoxonase 1 activity - studies in cultured cells, mice and humans

80%
Boesch-Saadatmandi C., Egert S., Schrader C., Coumoul X., Barouki R., Muller M. J., Wolffram S., Rimbach G.
Journal of Physiology and Pharmacology
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2010
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tom 61
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nr 1
99-105
There is increasing evidence that the HDL-associated enzyme paraoxonase 1 (PON1) may have a protective function in the atherosclerotic process. An enhancement of PON1 activity by dietary factors including flavonoids is therefore of interest. Quercetin, a flavonol frequently present in fruits and vegetables has been shown to induce PON1 in cultured liver cells, but the in vivo efficacy of a dietary quercetin supplementation has yet not been evaluated. To this end, we fed laboratory mice quercetin-enriched diets with quercetin concentrations ranging from 0.05 to 2 mg/g diet for 6 weeks and determined the expression of the hepatic PON1 gene and its protein levels. Since we could establish a moderate but significant induction of PON1 mRNA levels by dietary quercetin in mice, we aimed to proof whether healthy human volunteers, given graded supplementary quercetin (50, 100 or 150 mg/day) for two weeks, would respond with likewise enhanced plasma paraoxonase activities. However, PON1 activity towards phenylacetate and paraoxon was not changed following quercetin supplementation in humans. Differences between mice and humans regarding the PON1 inducing activity of quercetin may be related to differences in quercetin metabolism. In mice, unlike in humans, a large proportion of quercetin is methylated to isorhamnetin which exhibits, according to our reporter gene data in cultured liver cells, a potent PON1 inducing activity.
4

Effects of high sucrose diet, gemfibrozil, and their combination of plasma paraoxonase 1 activity and lipid levels in rats

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Macan M., Vrkic N., Vrdoljak L. A., Radic B., Bradamante V.
Acta Biochimica Polonica
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2010
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tom 57
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nr 3
 We investigated the influence of high sucrose diet (HSD) after 3 or 5 weeks of administration on paraoxonase 1 (PON1) activity in plasma of normolipidemic rats and the relationship between serum PON1 activity, triacylglycerides (TGs), HDL and total cholesterol vs. the control group of rats fed normal, control diet (CD). Because the data about the influence of gemfibrozil (GEM) on PON1 activity are controversial, we also investigated its effects (administration in the 4th and 5th week in rats on HSD and CD) on plasma PON1 activity and lipid levels in normolipidemic rats, and in rats with hypertriglyceridemia caused by HSD. Our results obtained in rats on HSD show a significant increase of plasma TGs levels by 47 % (P < 0.05) after 5 weeks of treatment, and PON1 activity by 32 % and 23 % (P < 0.05) after 3 and 5 weeks, but without change in lipid levels vs. rats on CD. In the rats on CD and HSD, GEM caused a significant decrease of PON1 activity by 44 % and 33 %, while a significant decrease of TGs level by 38 % (P < 0.05) was measured only in rats on CD. The effects of GEM on total cholesterol, HDL and LDL in both groups of rats were typical for its action on lipoprotein metabolism. Because GEM in the rat liver stimulates proliferation of peroxisomes, β oxidation, and production of H2O2, it is possible that the oxidative stress induced by GEM damages hepatocytes and lowers the synthesis of PON1.
5
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Protective effects of melatonin against thioacetamide-induced liver fibrosis in rats

80%
Czechowska G., Celinski K., Korolczuk A., Wojcicka G., Dudka J., Bojarska A., Reiter R. J.
Journal of Physiology and Pharmacology
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2015
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tom 66
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nr 4
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