Biomedical subjects

C Vergely

Publications and source records attributed to C Vergely.

25 records · Page 2Linked to original sources

PubMed1998

Direct evidence of caeruloplasmin antioxidant properties.

The chain-breaking antioxidant potential of caeruloplasmin and bovine serum albumin (BSA) has been investigated in comparison with other well-established antioxidants. Their Oxygen Radical Absorbing Capacity (ORAC), was measured by using beta-phycocyanin (beta-PC) as a fluorescent indicator protein, 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) as a peroxyl radical generator and the water soluble vitamin E analogue, Trolox, as a reference standard. The relative peroxyl absorbing capacities/mole for Trolox, caeruloplasmin, heat-denatured caeruloplasmin (hCP), catalase, bovine serum albumin (BSA), superoxide dismutase (SOD), and deferoxamine were 1; 2.6; 3.3; 3.7; 1.2; 0.1; 0.2, respectively. Caeruloplasmin was far more effective as a peroxyl radical scavenger than SOD, deferoxamine and BSA, but slightly less effective than catalase. The peroxyl radical absorbing capacity of caeruloplasmin was enhanced by heat-denaturation of the protein. Electron paramagnetic resonance (EPR) spectroscopy using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin-trap, was applied in order to measure the scavenger abilities of caeruloplasmin on superoxide radical and hydroxyl radical production and the concentration required to inhibit by 50% oxygen free radical formation (IC50) was determined. The IC50 values of caeruloplasmin, hCP, and BSA for the superoxide radical were 12, 2, 260 microM and for the hydroxyl radical 15, 2, 200 microM. These results show that caeruloplasmin is an effective chain-breaking antioxidant for a variety of radicals, independently of its catalytic ferroxidase activity.

Antioxidants↗

PubMed1998

Vitamin E analogues reduce the incidence of ventricular fibrillations and scavenge free radicals.

The aim of our study was to analyse the protective effects of different alpha-tocopherol analogues 1) against fibrillations induced by an ischemia-reperfusion sequence, and 2) to further investigate in vitro the radical scavenging properties of these analogues by two sensitive methods. Concerning 1: isolated rat hearts underwent 10 min of coronary ligation followed by reperfusion and the alpha-tocopherol analogues were infused 15 min before occlusion. Functional parameters including heart rate and fibrillations were recorded. Concerning 2: the beta-phycoerythrin assay was utilised to determine the oxygen radical absorbing capacity (ORAC) of these vitamin E analogues against peroxyl radicals. Electron paramagnetic resonance (EPR) was used to measure their scavenger abilities on hydroxyl radical and superoxide anion production. Concerning 1: ventricular fibrillation times were reduced for all analogues treated hearts at concentrations of 1 microM and 5 microM, with Trolox being the most efficacious. Concerning 2: in our experimental conditions of intense production of free radicals, scavenging IC50 values for hydroxyl radical were 1.15, 2.17 and 4.04 mM for Trolox, MDL 74270 and MDL 74366 respectively. Superoxide anion IC50 values were 1.0 and 6.75 mM for Trolox and MDL 74270. Our results show that water-soluble analogues of vitamin E are effective in the prevention of coronary ligation induced reperfusion arrhythmia, under our experimental conditions. Moreover, our data demonstrate that these vitamin E analogues are effective scavengers for a variety of radicals. Our studies support the view that compounds that can either inhibit the formation or scavenge free radicals can protect the heart against arrhythmia associated with ischemia-reperfusion.

Animals↗

PubMed1998

Studies by electron paramagnetic resonance of the importance of iron in the hydroxyl scavenging properties of ascorbic acid in plasma: effects of iron chelators.

Ascorbic acid is considered to be the most important antioxidant of plasma. Its oxidation leads to the ascorbyl free radical (AFR), detected by electron paramagnetic resonance (EPR) spectroscopy. The purpose of this study was to investigate by EPR the interaction of plasma AFR levels in different situations of oxidative stress. Our results showed that plasma AFR remains constant after rat feeding with vitamin C (5 mg or 50 mg per 100 g body weight). We also demonstrated that: (1) the ascorbyl free radical (AFR) level was increased after direct addition of iron Fe3+/EDTA to plasma, the optimal level was reached after addition of 8 microM Fe3+/EDTA (1:2); (2) this AFR production was associated with the formation of hydroxyl radicals. Iron chelators (deferrioxamine, a synthetic iron chelator and apotransferrine, a biological iron chelator) added just before the Fe3+/EDTA complex inhibited the increase of AFR signal induced by this complex. The scavenging effect of plasma was significantly correlated with the AFR production. Therefore, AFR, which is naturally present in plasma, could be used as an index of oxidative stress in which free radicals or adverse iron mobilisation are implicated.

Animals↗

PubMed1996

F1F0-ATPase, early target of the radical initiator 2,2'-azobis-(2-amidinopropane) dihydrochloride in rat liver mitochondria in vitro.

This study was designed to determine which enzyme activities were first impaired in mitochondria exposed to 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH), a known radical initiator. EPR spin-trapping revealed generation of reactive oxygen species although malondialdehyde formation remained very low. With increasing AAPH concentrations, State-3 respiration was progressively depressed with unaltered ADP/O ratios. A top-down approach demonstrated that alterations were located at the phosphorylation level. As shown by inhibitor titrations, ATP/ADP translocase activity was unaffected in the range of AAPH concentrations used. In contrast, AAPH appeared to exert a deleterious effect at the level of F1F0-ATPase, comparable with dicyclohexylcarbodi-imide, which alters Fo proton channel. A comparison of ATP hydrolase activity in uncoupled and broken mitochondria reinforced this finding. In spite of its pro-oxidant properties, AAPH was shown to act as a dose-dependent inhibitor of cyclosporin-sensitive permeability transition initiated by Ca2+, probably as a consequence of its effect on F1F0-ATPase. Resveratrol, a potent antiperoxidant, completely failed to prevent the decrease in State-3 respiration caused by AAPH. The data suggest that AAPH, when used under mild conditions, acted as a radical initiator and was capable of damaging F1F0-ATPase, thereby slowing respiratory chain activity and reducing mitochondrial antioxidant defences.

Amidines↗

PubMed1995

Quantitative image analysis of cell proliferation after balloon catheter injury in the rabbit carotid artery.

OBJECTIVE: To perform color image analysis to assess the course of morphometric and proliferative changes in the intima and media of rabbit carotid arteries following balloon injury. STUDY DESIGN: Proliferating smooth muscle cells were labeled with proliferating cell nuclear antigen and vizualized by immunohistochemical staining of histologic sections. Morphometry was performed on histologic cross-sections of injured arteries stained with hematoxylin. RESULTS: The development of intimal hyperplasia following an acute mechanical injury was detectable early on and was accompanied by a burst of cell proliferation. Medial cell proliferation peaked on day 3 after balloon injury, and the maximum of intimal cell proliferation was noted on day 7. CONCLUSION: The color image analysis method described here could be a useful tool in evaluating drugs for their ability to prevent restenosis.

Animals↗

PubMed1993

In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative.

N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]- phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918) has been selected from a chemical program aimed at identifying an optimized inhibitor of multidrug resistance (MDR). The potency of GF120918 is assessed by dose-dependent sensitization of CHRC5, OV1/DXR and MCF7/ADR cells to the cytotoxicity of doxorubicin and vincristine respectively: GF120918 fully reverses multidrug resistance at 0.05 to 0.1 microM and is half maximally active at 0.02 microM. The spectrum of drugs sensitized by GF120918 coincides with those having the classical MDR phenotype. In CHRC5 cells, 0.01-0.1 microM GF120918 enhances the uptake of [3H]daunorubicin and blocks the efflux from preloaded cells. It is also shown that GF120918 is still active several hours after being taken away from the culture medium showing that it is not, like verapamil, effluxed rapidly by P-glycoprotein. GF120918 effectively competes with [3H]azidopine for binding P-glycoprotein, pointing to this transport membrane protein as its likely site of action. After i.v. administration to mice, GF120918 penetrates thoroughly various organs that have a tissue level/blood level ratio above 10. It is eliminated from organs and blood with a half-time of approximately 2.7 h. It is well absorbed after p.o. administration. In mice implanted i.p. with the MDR P388/Dox tumor, a single i.v. or p.o. dose of GF120918 restores sensitivity of the tumor to a single i.p. dose (5 mg/kg) of doxorubicin administered 1 h later. A statistically significant effect is observed at 1 mg/kg GF120918 i.v. and maximal effect is reached at 5 mg/kg. Similarly, whereas neither drug alone is effective, GF120918 (10 mg/kg i.p.) associated with doxorubicin (5 mg/kg i.p.) inhibits the growth of the moderately MDR C26 tumor implanted s.c. as assessed by tumor size at day 19. GF120918 does not modify significantly the distribution or the elimination of doxorubicin in mice ruling out the possibility that the antitumor effects seen might be explained by pharmacokinetic interactions.

Acridines↗

PubMedDate not supplied

[A treatment with rosuvastatin induced a reduction of arterial pressure and a decrease of oxidative stress in spontaneously hypertensive rats].

The aim of this study was to appreciate consequences of rosuvastatin administration on hemodynamic function, vascular oxidative stress and ischemia/reperfusion disorders in normotensive and hypertensive rats. At 10 weeks of age, spontaneously hypertensive rats (SHR, n=20) and normotensive Wistar Kyoto male rats (WKY, n=20) were divided into four groups and given, either vehicle or 10 mg/kg/day of rosuvastatin by gavage for 3 weeks. Systolic blood pressure was assessed every week. At the end of these treatments, vascular NADPH oxidase activity was evaluated by chemiluminescence (lucigenin 0.5 microM). Hearts were isolated and perfused according to the Langendorff method and were subjected to 30 min of global ischemia. Reactive oxygen species (ROS) produced during reperfusion were quantified by electron spin resonance (ESR) spectroscopy using a spin probe (CP-H, 1 mM). After one week of treatment, rosuvastatin reduced the arterial pressure in SHR rats (180.3 +/- 2.1, SHR vs 169.7 +/- 2.3 mmHg, SHR+rosuvastatin; p < 0.01), without lowering plasma cholesterol levels; these effects were not observed in WKY. NADPH activity was 25% higher in control SHR rat aortas compared to control WKY, and was reduced by rosuvastatin in SHR rats. In isolated rat hearts subjected to ischemia/reperfusion sequences, there was a deterioration in functional parameters in control SHR compared to control WKY hearts. Rosuvastatin decreased post-ischemic contracture in WKY hearts by 50% (41.5 +/- 7.5, WKY control vs 18.4 +/- 4.6 mmHg, WKY+rosuvastatin; p < 0.01) and increased left ventricular developed pressure. This beneficial effect was accompanied by a decrease in ROS detected by ESR during reperfusion (312.5 +/- 45.3, WKY control; vs 219.3 +/- 22.9 AUC/mL, WKY+rosuvastatin; p < 0.05). In conclusion, these results are in accordance with the hypothesis that oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases including hypertension, and demonstrate the beneficial effects of rosuvastatin.

Animals↗