| 1. |
- Basu, Samar
(författare)
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F2-isoprostane induced prostaglandin formation in the rabbit
- 2006
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Ingår i: Free radical research. - : Informa Healthcare. - 1071-5762 .- 1029-2470. ; 40:3, s. 273-277
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Tidskriftsartikel (refereegranskat)abstract
- F2-isoprostanes, non-enzymatic free radical mediated products of arachidonic acid, have shown to form during various oxidant stress status and have potent biological effects. This study investigates to what extent 8-iso-PGF2α (a major F2-isoprostane), a bioactive product of lipid peroxidation can modify endogenous prostaglandin F2α (PGF2α) formation since prostaglandins are inflammatory as well as potent vasoregulatory substances that modulate diverse important physiological functions, and also form during acute and chronic inflammation. An immediate appearance and disappearance of 8-iso-PGF2α was seen in both plasma and urine within a short interval after i.v. administration of 43 μg/kg of 8-iso-PGF2α to the rabbits. A successive but differential formation of PGF2α resulted in a rapid and pulsatile increase of plasma 15-keto-dihydro-PGF2α, a major metabolite of primary PGF2α. Later, this compound was excreted efficiently as intact compound into the urine during the 3 h of experiment. A 8-fold increase of PGF2α metabolite in plasma at 10 min and 12-fold increase in the urine at 30–60 after the i.v. administration of 8-iso-PGF2α was observed which continued throughout the 3 h of experiment. This observation suggests that pharmacologically administered or endogenously produced 8-iso-PGF2α during oxidant stress induces prostaglandin formation presumbly through the classical cyclooxygenase-catalysed arachidonic acid oxidation which might be inflammatory itself to the cells and exerts further vasoconstrictive effects.
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| 2. |
- Basu, Samar, et al.
(författare)
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Regulatory factors of basal F(2)-isoprostane formation: population, age, gender and smoking habits in humans.
- 2009
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Ingår i: Free radical research. - : Informa UK Limited. - 1029-2470 .- 1071-5762. ; 43:1, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress is assumed to be the key underlying factor in the pathogenesis of many common diseases. This study describes the basal levels of 8-iso-PGF(2alpha ), a major F(2)-isoprostane and an in vivo oxidative stress biomarker in healthy subjects from three countries, namely Italy, Poland and Sweden, in relation to their smoking habits, age and gender. It studied urinary 8-iso-PGF(2alpha ) in 588 subjects from Sweden (n=220), Italy (n=203) and Poland (n=165). Polish subjects had the highest levels of F(2)-isoprostanes followed by the Swedish and Italians when adjusted for smoking, age, sex and creatinine and the inter-country differences were statistically significant. Smokers had significantly higher levels of 8-iso-PGF(2alpha ) compared to non-smokers in all countries and there was a moderate decrease with age. Women had only slightly lower 8-iso-PGF(2alpha ) than men. There is a difference in F(2)-isoprostane levels in vivo between countries. Smoking, age and gender affect isoprostane formation and should be taken into consideration in clinical studies of oxidative stress.
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| 3. |
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| 4. |
- Ehrlich, Kersti, et al.
(författare)
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Design, synthesis and properties of novel powerful antioxidants, glutathione analogues
- 2007
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Ingår i: Free radical research. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 41:7, s. 779-787
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Tidskriftsartikel (refereegranskat)abstract
- Glutathione (GSH) is the major low-molecular weight antioxidant in mammalian cells. Thus, its analogues carrying similar and/or additional positive properties might have clinical perspectives. Here, we report the design and synthesis of a library of tetrapeptidic GSH analogues called UPF peptides. Compared to cellular GSH our designed peptidic analogues showed remarkably higher hydroxyl radical scavenging ability (EC50 of GSH: 1231.0 +/- 311.8 mu M; EC50 of UPF peptides: from 0.03 to 35 mu M) and improved antiradical efficiency towards a stable alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical. The best of UPF peptides was 370-fold effective hydroxyl radical scavengers than melatonin (EC50: 11.4 +/- 1.0 mu M). We also found that UPF peptides do not influence the viability and membrane integrity of K562 human erythroleukemia cells even at 200 mu M concentration. Dimerization of GSH and UPF peptides was compared in water and in 0.9% saline solutions. The results, together with an earlier finding that UPF1 showed protective effects in global cerebral ischemia model in rats, suggest that UPF peptides might serve both as potent antioxidants as well as leads for design of powerful non-peptidic antioxidants that correct oxidative stress-driven events.
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| 5. |
- Gram, Magnus, et al.
(författare)
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The lipocalin alpha1-microglobulin protects erythroid K562 cells against oxidative damage induced by heme and reactive oxygen species.
- 2008
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Ingår i: Free Radical Research. - : Informa UK Limited. - 1029-2470 .- 1071-5762. ; 42:8, s. 725-736
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Tidskriftsartikel (refereegranskat)abstract
- Alpha(1)-microglobulin is a 26 kDa plasma and tissue glycoprotein that belongs to the lipocalin protein superfamily. Recent reports show that it is a reductase and radical scavenger and that it binds heme and has heme-degrading properties. This study has investigated the protective effects of alpha(1)-microglobulin against oxidation by heme and reactive oxygen species in the human erythroid cell line, K562. The results show that alpha(1)-microglobulin prevents intracellular oxidation and up-regulation of heme oxygenase-1 induced by heme, hydrogen peroxide and Fenton reaction-generated hydroxyl radicals in the culture medium. It also reduces the cytosol of non-oxidized cells. Endogeneous expression of alpha(1)-microglobulin was up-regulated by these oxidants and silencing of the alpha(1)-microglobulin expression increased the cytosol oxidation. alpha(1)-microglobulin also inhibited cell death caused by heme and cleared cells from bound heme. Binding of heme to alpha(1)-microglobulin increased the radical reductase activity of the protein as compared to the apo-protein. Finally, alpha(1)-microglobulin was localized mainly at the cell surface both when administered exogeneously and in non-treated cells. The results suggest that alpha(1)-microglobulin is involved in the defence against oxidative cellular injury caused by haemoglobin and heme and that the protein may employ both heme-scavenging and one-electron reduction of radicals to achieve this.
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| 6. |
- Helmersson, Johanna, et al.
(författare)
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Serum selenium predicts levels of F2-isoprostanes and prostaglandin F2alpha in a 27 year follow-up study of Swedish men
- 2005
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Ingår i: Free radical research. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 39:7, s. 763-770
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Tidskriftsartikel (refereegranskat)abstract
- Low concentrations of selenium (Se) predict mortality and cardiovascular diseases in some populations. The effect of Se on in vivo indicators of oxidative stress and inflammation, two important features of atherosclerosis, in human populations is largely unexplored. This study investigated the longitudinal association between serum selenium (s-Se) and a golden standard indicator of oxidative stress in vivo (8-iso-prostaglandin F2, a major F2-isoprostane), an indicator of cyclooxygenase (COX)-mediated inflammation (prostaglandin F2), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and serum amyloid A protein (SAA) in a follow-up study of 27 years. The s-Se was measured in 615 Swedish men at 50 years of age in a health investigation. The status of oxidative stress and inflammation was evaluated in a re-investigation 27 years later by quantification of urinary 8-iso-PGF2 and 15-keto-dihydro- PGF2 (a major metabolite of PGF2) and serum hsCRP, SAA and IL-6. Men in the highest quartile of s-Se at age 50 had decreased levels of 8-iso-PGF2 compared to all lower quartiles and decreased levels of PGF2 compared to all lower quartiles at follow-up. These associations were independent of BMI, diabetes, hyperlipidemia, hypertension, smoking, -tocopherol and β-carotene at baseline. The s-Se was not associated with hsCRP, SAA or IL-6 at follow-up. In conclusion, high concentrations of s-Se predict reduced levels of oxidative stress and subclinical COX-mediated (but not cytokine-mediated) inflammation in a male population. The associations between Se, oxidative stress and inflammation, respectively, might be related to the proposed cardiovascular protective property of Se.
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| 7. |
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| 8. |
- Li, Wei, et al.
(författare)
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7ß-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization
- 2009
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Ingår i: Free radical research. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 43:11, s. 1072-1079
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral natural killer (NK) cells are reduced in patients with coronary artery disease and highly susceptible to apoptosis induced by oxidized lipids including 7beta-hydroxycholesterol (7betaOH) in vitro. The present study aimed to further explore the mechanisms behind 7betaOH-mediated cytotoxicity to human NK cells. Human NK cells were purified and treated with 7betaOH in different concentrations and times. Cell death, lysosomal and mitochondrial permeabilization and reactive oxygen species (ROS) production were then analysed. The 7betaOH induced time and dose dependent apoptosis and necrosis in human NK cells, which was preceded by loss of lysosomal integrity and enhanced ROS production. At later time points, the mitochondrial membrane permeability in 7betaOH-treated cells was significantly increased. The findings indicate that 7betaOH induces human NK cell death through early lysosomal permeabilization and consequent oxidative stress. The data further suggest that 7betaOH may induce immune disturbances in clinical settings such as atherosclerosis.
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| 9. |
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| 10. |
- Palm, Maria, et al.
(författare)
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F(2)-isoprostanes, tocopherols and normal pregnancy
- 2009
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Ingår i: Free radical research. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 43:6, s. 546-552
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates oxidative stress and antioxidants in normal human pregnancy and post-partum period. Thirty-seven healthy women with normal pregnancies were included. Both urinary and serum samples were collected throughout the pregnancy and post-partum period. Oxidative stress was estimated by measuring the reliable in vivo marker, namely 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha,) an F(2)-isoprostane) and antioxidant status was evaluated by measuring alpha- and gamma-tocopherol in serum samples. Pregnancy was associated with successively increased levels of 8-iso-PGF(2alpha) with advancing gestational age. The median post-partum value corresponded to the values observed in early gestation and a significant decrease was observed from late pregnancy to the post-partum period. Lipid-adjusted alpha- and gamma-tocopherol levels decreased with advancing gestational age. This longitudinal study suggests that mild oxidative stress is involved in normal human pregnancy.
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