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Biomedical subjects

C Rice-Evans

Publications and source records attributed to C Rice-Evans.

At least 73 records · Page 4Linked to original sources
PubMed1993

A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates.

1. A new method has been developed for measuring the total antioxidant capacity of body fluids and drug solutions, based on the absorbance of the ABTS.+ radical cation. 2. An automated method for use on a centrifugal analyser, as well as a manual method, is described. 3. The procedure has been applied to physiological antioxidant compounds and radical-scavenging drugs, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard. 4. The Trolox equivalent antioxidant capacity of plasma from an adult reference population has been measured, and the method optimized and validated. 5. The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity.

Adult↗
PubMed1993

Comparison of N-methyl hexanoylhydroxamic acid, a novel antioxidant, with desferrioxamine and N-acetyl cysteine against reperfusion-induced dysfunctions in isolated rat heart.

The effects of a novel free radical scavenger, N-methyl hexanoylhydroxamic acid (NMHH) on ischaemia and reperfusion-induced dysfunction were compared with those of desferrioxamine (DFO) and N-acetyl cysteine (NAC) in isolated Langendorff-perfused rat heart. NMHH (150 microM) produced significant improvement in recovery of left ventricular developed pressure (LVDP) as compared with that of control hearts (35 +/- 8%) when included in the perfusate both before ischaemia and on reperfusion (68 +/- 6%) and on reperfusion alone (61 +/- 6%). In contrast, neither DFO (52 +/- 9%) nor NAC (54 +/- 12%), at the same concentration, produced a significant increase in recovery of LVDP when applied on reperfusion alone. Only DFO (77 +/- 5%), not NAC (54 +/- 12%), had a significant effect on recovery of LVDP when added to the perfusate before ischaemia and reperfusion. NAC applied before ischaemia produced significant improvement in recovery of heart rate (HR). The improved recovery of LVDP obtained with NMHH applied on reperfusion as compared with that obtained with controls and equimolar concentrations of DFO or NAC suggests that the novel hydroxamate NMHH is the more effective in attenuating reperfusion injury of contractile function in this model.

Acetylcysteine↗
PubMed1993

Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin.

Plasma coenzyme Q (CoQ) was measured in 20 hyperlipidaemic patients treated with diet and simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase); 22 hyperlipidaemic patients treated with diet with alone; and 20 normal controls. Patients treated with simvastatin had a significantly lower plasma CoQ and CoQ: cholesterol ratio than either patients receiving diet alone or normal controls. Use of simvastatin was inversely and independently correlated with both CoQ (p < 0.0001) and CoQ: cholesterol ratio (p < 0.01). There was a significant inverse association between CoQ and dose of simvastatin (p < 0.001). It is concluded that simvastatin may lower the plasma CoQ concentration and this may be greater than the reduction in cholesterol. The possible adverse effect of simvastatin on the metabolism of CoQ may be clinically important and requires further study.

Adult↗
PubMed1993

The effects of N-methyl butyrohydroxamic acid and other monohydroxamates on reperfusion-induced damage to contractile function in the isolated rat heart.

The effects of three novel methyl substituted monohydroxamates N-methyl butyrohydroxamic acid (NMBH), N-methyl acetohydroxamic acid (NMAH) and N-methyl benzohydroxamic acid (NMBzH) against reperfusion induced contractile dysfunction were investigated in the isolated Langendorff-perfused rat heart. All these drugs produced an improved recovery of left ventricular developed pressure (LVDP) compared to control hearts in the order NMBH* (65 +/- 8%) > NMAH (59 +/- 8%) > NMBzH (48 +/- 3%) > control (35 +/- 3%) (mean +/- s.e.), however only the recovery obtained in NMBH treated hearts was significantly different from control hearts (*p > 0.05, Dunnett's test). Both NMAH (98 +/- 10%) and NMBH (84% +/- 8) produced a significant improvement in the recovery of heart rate (control 48 +/- 13%). There was no significant improvement of coronary flow, and NMBzH-treated hearts showed a significant reduction in recovery. The improved recovery in both LVDP and heart rate obtained with NMBH suggests this drug may be effective in attenuating reperfusion-induced contractile dysfunction in the isolated rat heart. Further, a comparison of the structures of the hydroxamates described in this study with the results obtained with desferrioxamine, (a trihydroxamate), and N-methyl hexanoylhydroxamic acid (NMHH) in other studies suggests that the nature of the alkyl chain attached to the carbonyl group of the hydroxamate may contribute to the efficacy of monohydroxamates in attenuating this type of myocardial injury in this model.

Animals↗
PubMed1993

Reduction of a tetrazolium salt and superoxide generation in human tumor cells (HeLa).

Experiments have been carried out to explore the use of a tetrazolium salt, MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide in the detection of intracellularly generated superoxide in HeLa cells. From the use of a low molecular weight lipophilic mimic of superoxide dismutase, as well as superoxide dismutase, and inhibitors of superoxide dismutase, it is suggested that at least 20-30% of the intracellular reduction of MTT is due to superoxide. Whilst this may arise from mitochondria another possible intracellular source in HeLa cells may be xanthine oxidase. The overall rate of intracellular MTT reduction in HeLa cells is inversely dependent on levels of serum in the culture medium. Serum components with a modulatory role in this context are those with antioxidant function. Reduced MTT is also detectable extracellularly in cultures of HeLa cells and at least 80% of this is due to superoxide. Use of inhibitors suggest that whilst a small proportion (30%) may arise through an NADPH-oxidase type enzyme, other sources of extracellular superoxide in HeLa cells remain a possibility.

Allopurinol↗
PubMed1992

The interaction between ruptured erythrocytes and low-density lipoproteins.

Low-density lipoproteins (LDL) are oxidatively modified on interaction with haem proteins. The interaction of ruptured erythrocytes with LDL induces oxidative damage as detected by alterations in electrophoretic mobility and the peroxidation of the polyunsaturated fatty acyl chains. Difference spectroscopy reveals that the amplification of the oxidative process by the haem protein is related to the transition of the oxidation state of the haemoglobin in the erythrocyte lysate from the oxy [X-FeII-O2] to the ferryl [X-FeIV = O] form. The incorporation of the lipid-soluble antioxidant, butylated hydroxy toluene, at specific time points during the LDL-erythrocyte interaction prolongs the lag phase to oxidation and eliminates the oxy-to-ferryl conversion of the haemoglobin. The timescale of this haem conversion is related to the antioxidant status of the LDL.

Erythrocytes↗
PubMed1992

Variable alpha-tocopherol stimulation and protection of glutathione peroxidase activity in non-transformed and transformed fibroblasts.

Studies on glutathione metabolism in an established baby hamster kidney cell line (BHK-21/C13) and in its polyoma virus-transformed counterpart (BHK-21/PyY), have revealed a significant stimulation of intracellular glutathione peroxidase activity (Se-independent plus Se-dependent) by alpha-tocopherol supplementation (14 microM). This stimulation was found to be much greater in the transformed cells. Other GSH-requiring enzyme activities (namely glutathione reductase and glutathione transferase) were unaltered by alpha-tocopherol treatment, suggesting a degree of specificity in its action on GSHpx. In unsupplemented growth media, the GSHpx activity in both cell lines was significantly decreased by an oxidative stress. However, the same stress applied to the alpha-tocopherol-supplemented cells had no effect on the stimulated GSHpx activity, suggesting a protection afforded by the alpha-tocopherol.

Animals↗
PubMed1992

The chelation of nonheme iron within sickle erythrocytes by the hydroxypyridinone chelator CP094.

Nonheme, nonferritin iron has been detected in membrane preparations from sickle erythrocytes and has been suggested to catalyze free radical reactions in these cells contributing to the development of membrane oxidation. In this study the hydroxypyridinone iron chelator, CP094, currently being evaluated as a potentially therapeutic chelator, and desferrioxamine have been studied for their abilities to chelate the nonheme iron within intact sickle erythrocytes under physiological conditions. The results suggest that CP094 can enter sickle erythrocytes, chelate nonheme iron and suppress membrane lipid peroxidation within a timescale in which desferrioxamine does not enter the cells. Suppression of lipid peroxidation showed no protective effect in an in vitro system inducing the formation of irreversibly sickled cells.

Anemia, Sickle Cell↗
PubMed1992

Thiol compounds as protective agents in erythrocytes under oxidative stress.

The potential for the thiol-containing drugs, N-acetyl cysteine and N-mercaptopropionyl glycine, to act as antioxidants intracellularly has been studied in erythrocytes under oxidative stress. The effects have been compared with that of the glutathione peroxidase inhibitor, mercaptosuccinate. The results show differential responses of sickle and normal erythrocytes to the thiol compounds. N-acetyl cysteine is the more efficacious with no toxic effects in these systems. N-Mercaptopropionyl glycine is not only limited in its ability to demonstrate antioxidant capacity in erythrocytes but also exerts deleterious effects.

Acetylcysteine↗
PubMed1992

Variable alpha-tocopherol stimulation and protection of glutathione peroxidase activity in established and malignant fibroblasts.

Studies on glutathione (GSH) metabolism in an established baby hamster kidney fibroblast cell line (BHK-21/C13) and in its polyoma virus-transformed counterpart (BHK-21/PyY) have revealed a significant stimulation of intracellular GSH peroxidase (GSHpx) activity (selenium-independent plus selenium-dependent) by alpha-tocopherol supplementation (14 microM). This stimulation was found to be much greater in the transformed cells. Other GSH-requiring enzyme activities (i.e. GSH reductase and GSH S-transferase) were unaltered by alpha-tocopherol treatment, suggesting a degree of specificity in its action on GSHpx. In unsupplemented growth media, the GSHpx activity in both cell lines was significantly decreased by oxidative stress. However, the same stress applied to the alpha-tocopherol-supplemented cells had no effect on the stimulated GSHpx activity, suggesting that some protection was afforded by the alpha-tocopherol.

Animals↗
PubMed1991

The modulation of ferryl myoglobin formation and its oxidative effects on low density lipoproteins by nitric oxide.

This study has investigated the interactions between nitric oxide and haem protein radicals. The results demonstrate that nitric oxide interacts with activated ferryl myoglobin species with reduction to metmyoglobin, but the extent and duration of the reduction depends on the relative concentrations of nitric oxide and hydrogen peroxide. Ferryl myoglobin has a much greater relative potential for oxidising polyunsaturated fatty acid side chains in low density lipoproteins than in cell membranes. The peroxidative response can be modulated by nitric oxide: ferryl myoglobin-mediated peroxidation of LDL may be enhanced or suppressed by nitric oxide depending on the relative concentrations of NO and hydrogen peroxide.

Erythrocyte Membrane↗