Biomedical subjects

P M Filipe

Publications and source records attributed to P M Filipe.

11 recordsLinked to original sources

PubMed1998

[Antioxidant effect of drugs used in cardiovascular therapy].

Oxidative stress is implicated in the pathogenesis of various cardiovascular disorders. The knowledge, characterisation and comparison of the different antioxidant properties of some cardiovascular drugs might lead to new therapeutic approaches. Blood constituents are biological products easier to obtain. Their oxidative damage is accepted to be involved in several pathogenic pathways such as atherogenesis. Blood products can be utilised as in vitro models of macromolecular and cellular oxidative damage. It is well known that transition metals catalyse the generation of more damaging reactive oxygen species. We studied the antioxidant effect of four beta-adrenergic blocking agents (pindolol, propranolol, atenolol and metoprolol) and of one calcium channel antagonist (nifedipine), on the plasma oxidative damage induced by copper. Lipid peroxidation was evaluated by measuring fluorescent substances. We added the drugs to the assay system, before and after the induction of peroxidation by copper, to elucidate their ability to prevent and/or block lipid peroxidation. We observed that pindolol, propranolol and nifedipine have antioxidant properties, in the assay system, when added 15 min before the addition of copper. This effect is demonstrated by the delay in initiation and decrease in formation of lipid peroxidation products. Nifedipine also has a remarkable chain breaking effect. We compared the drugs with ascorbic acid in their relative antioxidant effect: nifedipine > ascorbate > pindolol > propranolol.

Adrenergic beta-Antagonists↗

PubMed1997

Lipid peroxidation in type 2 normolipidemic diabetic patients.

Vascular complications, as a consequence of atherosclerosis, are the main causes of morbidity and mortality in diabetes. Low density lipoprotein (LDL) oxidation is accepted as a relevant pathogenic mechanism in atherogenesis. The aim of this work was to study the relationship between lipid peroxidation (LPO) and metabolic control. LPO was evaluated in 40 type 2 normolipidemic diabetic patients by measuring thiobarbituric acid reactive substances (TBARS), in the plasma, using malondialdehyde (MDA), end product of the oxidation of polyunsaturated fatty acids, as a standard. Fast blood glucose (FBG), serum total cholesterol (TC) and serum triglycerides (TG) were evaluated by routine methods. Fructosamine (FR) was measured by the nitroblue tetrazolium (NBT) colorimetric test. An elevated level of lipid peroxides (P < 0.001) was observed in the plasma of diabetic patients (4.51 +/- 1.29 nmol/ml) as compared to normal subjects (3.54 +/- 1.00 nmol/ml). Lipid peroxides did not correlate with the FR levels, nor with FBG, TC and TG. These results show an increase of LPO in type 2 normolipidemic diabetic patients. Probably the mechanism for higher lipid peroxide levels in diabetes is multifactorial. Our study supports the hypothesis of a role of oxidative stress in diabetes independently of the lipid serum content.

Aged↗

PubMed1997

[Effect of silibinin on oxidative damage of blood constituents].

Silibinin (SDH) is a flavonoid with ascertained hepatoprotective effects, which have been partially attributed to its antioxidant properties. Oxidation of blood constituents could have a role in atherogenesis and interfere with the rheologic properties of the blood. In this study we investigated, whether SDH could protect some blood constituents against oxidative modification. In human plasma we measured TBARS and fluorescence generation as indicators of copper or azobis amidinopropane hydrochloride (AAPH) at 760 mm Hg PO2-induced lipid peroxidation. SDH at 50 microM inhibited copper-induced TBARS formation by 25% and fluorescence by 47%. SDH also inhibited AAPH-induced lipid peroxidation, but at 175 microM concentration only. Oxidative modification of albumine was evaluated by fluorescence generation. SDH at 50 microM inhibited copper/hydrogen peroxide fluorescence generation by 54% and at 2.5 microM it inhibited EDTA-Fe (II)/hydrogen peroxide fluorescence generation by 31%. The protection of albumin by SDH was confirmed by SDS-PAGE electrophoresis. Copper-induced red-cell lipid peroxidation was evaluated by TBARS formation. SDH at 250 microM inhibited copper-induced lipid peroxidation and hemolysis by 45% and 94%, respectively. SDH also inhibited hemolysis in red-cell suspensions exposed to hydrogen peroxide, but not lipid peroxidation. Our results show that SDH may protect blood constituents from oxidative damage.

Blood↗

PubMed1996

Different effects of thiol and nonthiol ace inhibitors on copper-induced lipid and protein oxidative modification.

Differences among angiotensin-converting enzyme inhibitors (ACEI) in scavenging reactive oxygen species were described and mainly attributed to the presence or absence of a thiol group. Plasma constituents and red cells are known targets for oxidative damage. Transition metals, like copper, are well known catalizers of free radical generation. In the present study we compared the abilities of captopril (a thiol ACEI), enalaprilat, and lisinopril (two nonthiol ACEI) for inhibiting copper-induced thiobarbituric acid reactive substances (TBARS) formation and fluorescence generation in whole human plasma and low-density lipoprotein. The effects of those ACEI on copper/hydrogen peroxide-induced fluorescence development and electrophoretic mobility modification in albumin and on copper-induced TBARS formation and hemolysis in human red cells were also compared. Captopril was more effective than the two nonthiol ACEI in inhibiting plasma and LDL lipid peroxidation, but it was ineffective in inhibiting the albumin oxidative modification that was moderately inhibited by enalaprilat and lisinopril. On the contrary, the inhibitory effects of the three ACEI on copper-induced lipid peroxidation and hemolysis in red cell suspensions were more uniform. This as yet unreported red cell protective effect may deserve pharmacological evaluation. Our results show that captopril is a more effective antioxidant than the nonthiol ACEI in some systems. However, the nonthiol ACEI also have the ability to partially protect some targets against oxidative damage. These observations suggest that the presence of a thiol group in the ACEI structure is not the only determinant for the antioxidant properties.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

[Lipid peroxidation, production of PGE2 and cellular mortality induced by UV in cultured human skin fibroblasts].

UV irradiation induces lipid peroxidation (LPO) and cell damage. The aim of the present work was the study of UVB radiation effects on cultured human skin fibroblasts, concerning LPO, prostaglandine E2 (PGE2) formation and cell viability. The cells were exposed to 50, 100, and 150 mJ/cm2 of UVB irradiation. Cellular TBARS and supernatant fluorescent substances were measured spectrofluorimetrically. PGE2 was measured using an immunoenzymatic method. Cell viability was evaluated by the MTT test. All determinations were done after a 2 h incubation period post-irradiation. TBARS were increased for all doses of irradiation (p < 0.001). Fluorescent substances differed from controls at 50 mJ/cm2 (p < 0.001). UVB at 100 and 150 mJ/cm2 decreased cellular viability (p < 0.001). An increase of PGE2 was observed with UVB at 150 mJ/cm2 (p < 0.001). These results confirm the occurrence of LPO and cytotoxicity after UV irradiation; on the other hand, this study showed the formation of PGE2 induced by UV light on cultured human skin fibroblasts. We propose a relationship between these phenomena.

Cell Death↗

PubMed1994

[Stress proteins].

Cells from all organisms have developed a remarkable number of strategies to deal with adverse changes in their environment. One of these protective mechanisms is the heat shock response, or stress response, characterized by the extremely rapid increased expression of a selected group of proteins--the heat shock proteins (hsp)--after a sudden increase in the normal cellular growth temperature. The same response takes place when cells are subjected to a wide variety of other stressors: a) environmental assaults: exposure to heavy metals, alcohols, inhibitors of energy metabolism, amino acid analogues; b) states of disease: ischemia, oxidative injury, infectious diseases, immunity disorders and malignancy. On the other hand, some hsp are believed to play an important role in protein maturation steps and in cellular development and differentiation. The understanding of stress response is still incomplete but the promise of its medical applications for fighting against ischemia, infection, immunity diseases and cancer is clearly on the horizon.

Heat-Shock Proteins↗

PubMed1992

Protective effects of a 21-aminosteroid against copper-induced erythrocyte and plasma lipid peroxidation.

The 21-aminosteroids, or lazaroids, are a novel class of antioxidant drugs designed to inhibit iron-dependent lipid peroxidation in biological lipid environments. They have been shown to be of therapeutic value in several animal models of traumatic, ischemic and hemorrhagic injury of the central nervous system. Our purpose was to evaluate the ability of 21-aminosteroids to protect human erythrocytes and plasma against oxidative damage in vitro. We found that the 21-aminosteroid U74500A inhibited erythrocyte and plasma lipid peroxidation. U74500A at 1 microM significantly reduced copper-induced and hydrogen peroxide-induced erythrocyte lipid peroxidation by 76.5 and 27.6%, respectively. The inhibition of erythrocyte lipid peroxidation was accompanied by an inhibition of hemolysis. Copper-induced plasma lipid peroxidation was also significantly reduced by as little as 1 microM U74500A. These results suggest that 21-aminosteroids may prove useful in preventive or therapeutic interventions in situations where erythrocyte or plasma components are subjected to oxidative stress and in situations related to copper-induced oxidative damage.

Antioxidants↗

PubMed1991

The inhibition of lipid peroxidation by cinnarizine. Possible implications to its therapeutic and side-effects.

Cinnarizine has antivasoconstrictor properties and improves red-cell deformability. Its major side-effects are the induction of extrapyramidal reactions. It is a calcium antagonist, but it was suggested that its effects may depend on other mechanisms, namely on antiperoxidant properties. We have studied these properties in different biological systems, intact red-cells included. The occurrence of lipid peroxidation was determined by the formation of 2-thiobarbituric acid reactive products. Cinnarizine was found to inhibit spontaneous lipid peroxidation in rat liver homogenates, copper-induced lipid peroxidation in human plasma and copper-induced and hydrogen peroxide-induced lipid peroxidation in human red-cells. In red-cells, the inhibition of lipid peroxidation is accompanied by the inhibition of hemolysis. Copper-induced red-cell lipid peroxidation is 85% inhibited by as little as 5 microM cinnarizine. The antioxidant activity of cinnarizine may contribute to explain some of the effects of this drug.

Animals↗

PubMedDate not supplied

Effects of zinc on copper-induced and spontaneous lipid peroxidation.

Zinc (Zn) is an essential nonredox metal that has been regarded as having antioxidant properties. Some epidemiological indications and therapeutic results point to a role of Zn in restricting the development and the progression of some diseases. Redox-active metals like iron and copper are involved in oxidative injury mechanisms, and a decrease in the Zn:Cu ratio may be associated with certain pathologies. We studied the effect of Zn on the copper-induced lipid peroxidation in diluted human plasma. Lipid peroxidation was evaluated by measuring the formation of conjugated dienes and of thiobarbituric acid reactive products. We found that 20 microM Zn reduced the 125-microM copper-dependent formation of conjugated dienes by 27% and of thiobarbituric acid reactive products by 49%, during a 3-h incubation period. The inhibition of lipid peroxidation by 125 microM Zn is almost total in the same conditions. The time-course study of the inhibitory effect of 125 microM Zn showed that it lasted for 7 h, which was the maximum incubation period tested. We also found that Zn had an inhibitory effect on the spontaneous lipid peroxidation in rat brain whole homogenates. Our results support the antioxidant properties of Zn, which may be potentially relevant to the protection of human plasma constituents, competing with the transition metals for redox reactions.

Animals↗

PubMedDate not supplied

Pentoxifylline. A hydroxyl radical scavenger.

Pentoxifylline (PTX), a tri-substituted purine and xanthine derivative, has been used for several years to improve microcirculation because of its hemorheological properties. PTX has also antifibrotic and anti-inflammatory effects. We studied the reaction of PTX with the hydroxyl radical and superoxide anion. Hydroxyl radical was generated by a mixture of ascorbic acid, H2O2 and Fe(III)-EDTA. We evaluated the iron-dependent degradation of deoxyribose, mediated by hydroxyl radical, in the presence of different concentrations of PTX (from 0.05 to 3 mM), measuring the degradation products of deoxyribose that react with 2-thiobarbituric acid (TBA). The reaction of PTX with hydroxyl radical occurred with a rate constant of (1.1 +/- 0.2) x 10(10) M-1/s. These results support the properties of PTX as a hydroxyl radical scavenger. Some authors verified that PTX decreases the release of superoxide anion from activated neutrophils. We studied the effect of PTX as a scavenger of superoxide generated in vitro by a hypoxanthine-xanthine oxidase system. PTX was not a superoxide anion scavenger in this system.

Ascorbic Acid↗

PubMedDate not supplied

[Ketanserin as antioxidant].

Free radicals have been related to the pathogenesis of some cardiovascular diseases. Several drugs used to treat these diseases were shown to have antioxidant properties. Our purpose was to evaluate if ketanserin, a selective S2 receptor antagonist with proven antihypertensive efficacy and which beneficially affects hemorheology, also is able to inhibit lipid peroxidation. Lipid peroxidation was induced in different biological systems in vitro and evaluated by the formation of thiobarbituric acid-reactive products. Ketanserin 50 microM inhibited copper-dependent lipid peroxidation in human red-cell suspensions by 40.8% and the subsequent hemolysis by 57,3%. It was less efficient in inhibiting hydrogen peroxide-dependent lipid peroxidation and hemolysis in the same system. Ketanserin 100 microM inhibited lipid peroxidation induced by a mixture of copper(II) and hydrogen peroxide in hepatic microsomal suspensions and in brain total homogenates by 86.2% and 56.7%, respectively. These results proved an antioxidant effect for ketanserin which was unknown, although its therapeutic relevance remains undetermined.

Animals↗