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Biomedical subjects

I Mavelli

Publications and source records attributed to I Mavelli.

At least 37 records · Page 2Linked to original sources
PubMed1987

Prevention by fructose-1,6-bisphosphate of cardiac oxidative damage induced in mice by subchronic doxorubicin treatment.

An experimental model of mild, subchronic doxorubicin cardiotoxicity in mice was investigated by monitoring changes of biochemical parameters related to cell response against oxidative stress in both liver and heart. A specific increase of the lactate dehydrogenase isoenzyme typical of the heart was observed for doxorubicin-treated mice. Lipid peroxidation, as evaluated by malondialdehyde determination, and catalase activity were greatly increased in heart and unaffected in liver. On the other hand, these changes can be considered as indicative of early heart damage induced by doxorubicin. Glutathione, glutathione peroxidase, and 6-phosphogluconate dehydrogenase values were not significantly altered by the treatment and glucose-6-phosphate dehydrogenase increased in both liver and heart. Administration of fructose-1,6-bisphosphate strongly reduced the increase of plasma lactate dehydrogenase, heart lipid peroxidation, and heart catalase while no effect on the diagnostically irrelevant increase of glucose-6-phosphate dehydrogenase was observed. The inhibitory effect on the onset of biochemical modification typical of early subchronic doxorubicin cardiotoxicity may be related to stimulation of ATP synthesis by fructose-1,6-bisphosphate and is therapeutically promising in view of the lack of toxicity of fructose-1,6-bisphosphate as a drug.

Animals↗
PubMed1987

Evidence for superoxide generation from the autoxidation of the favism-inducing aglycone divicine.

The formation of the superoxide anion radical (O2-) during the autoxidation of divicine, an unstable aglycone involved in the hemolytic anemia occurring in favism, has been demonstrated by EPR with two different procedures. In the first case (chemical method) an O2--mediated reduction of a nitroxide by cysteine was shown to occur when divicine was allowed to cycle between the oxidized and the reduced form. In the second case (enzymatic method) the specific reaction between superoxide and superoxide dismutase was used as superoxide detector. It was shown that the enzyme attained a steady-state condition when mixed with divicine in the presence of air, as monitored by EPR evaluation of the oxidation state of the catalytic copper: this result is a direct, specific indicator of an O2- flux.

Cyclic N-Oxides↗
PubMed1986

Effect of the redox state of the red blood cell components on the inactivation of glutathione peroxidase by divicine.

The redox state of red blood cell components was found to have profound effects on the specific inactivation of erythrocyte glutathione (GSH) peroxidase by divicine, a hydroquinone imine molecule of fava beans likely to be responsible, through redox cycling, of the oxidative damage of red blood cells ultimately resulting in the hemolysis of favism. Oxidation of hemoglobin is a necessary step for the inactivation to take place, apparently as a H2O2-MetHb adduct. On the other hand, the presence of either reduced NADP or glutathione enhances the inactivating effect although NADPH inhibits the oxidation of hemoglobin, and this suggests a catalytic role for MetHb in the inactivation process.

Ascorbic Acid↗
PubMed1985

Inactivation of red cell glutathione peroxidase by divicine and its relation to the hemolysis of favism.

A significant inactivation of red blood cell glutathione peroxidase (25% less than the physiological value) was observed after exposure of intact erythrocytes to 2 mM divicine (an autoxidizable aminophenol from Vicia faba seeds) and 2 mM ascorbate for 3 h at 37 degrees C. Addition of catalase and conversion of Hb to the carbomonoxy derivative resulted in protection against enzyme inactivation. Oxidation of Hb was a concurrent phenomenon, and augmented the inactivating effect. In hemolysates, much stronger effects were observed at shorter times (2 h); divicine was effective also without ascorbate, and the presence of reductants (ascorbate or glutathione or NADPH) enhanced its inactivating power. Of the other antioxidant enzymes, superoxide dismutase was unaffected under the same experimental conditions. Catalase was found to be much less sensitive to the inactivation; it was almost unaffected in experiments with intact erythrocytes and specifically protected by NADPH in experiments with hemolysates. This specific damage of glutathione peroxidase, apparently involving interaction of H2O2 and HbO2, may be related to the pathogenesis of hemolysis in favism.

Adult↗
PubMed1985

11p13 deletion and reduced RBC catalase in a patient with aniridia, glaucoma and bilateral Wilms' tumor.

A rare case of a one-year-old child with Wilms' tumor, aniridia and glaucoma is described, in whom bone marrow chromosome analysis showed the presence of an interstitial microdeletion on the short arm of chromosome 11, presumably involving the p13 band. Research of the enzyme activity of RBC catalase showed a 40% reduction. This finding is compatible with the loss of the 11p13 band which contains the gene coding this enzyme. 11p13 deletion in Wilms' tumor and 13q interstitial deletion in retinoblastoma provide a rare case of prezygotic chromosome abnormality, which may be considered to have a determinant role in the tumor etiopathogenesis.

Catalase↗
PubMed1985

Biochemical mechanism of oxidative damage by redox-cycling drugs.

Biochemical mechanisms of production of redox intermediates of redox-cycling drugs include: photochemical events, either photoionization process or electron transfer from photoexcited states; electron exchange of reduced form of a drug with the oxy state of oxygen-binding hemoproteins; oxidation by catalytic metal centers (oxidases, peroxidases, oxygenases) of the reduced forms of drugs; or electron transfer to the oxidized form of a drug from activated intracellular electron transfer chain (mitochondria, microsomes, etc.). Further reaction of these drug free radicals can lead to oxidative damage by either direct attack of biological macromolecules or via oxygen reduction, giving O2-, H2O2, and OH. The reaction pathway depends on the presence of metal ions, natural scavengers, enzymes that control relative concentrations of reactive species, and availability of oxygen in the environment.

Animals↗
PubMed1985

Effect of ischemia on heart submitochondrial superoxide production.

NADH-dependent formation of superoxide anions (O2-) by rabbit cardiac submitochondrial particles (SMP) was stimulated after exposure of the isolated heart to 90 min of ischemic perfusion. This effect was more evident in the rotenone-inhibited region of the respiratory electron chain in comparison to the antimycin-inhibited region. The kinetic study of the NADH-dependent reaction showed that at the level of the rotenone-inhibited region, ischemia reduced Km value for NADH, differently from the antimycin-inhibited region where the kinetic constants remain unchanged. No significant changes of the Vmax values were observed in both SMP-producing O2- sites. The ischemic perfusions also produced a reduction of mitochondrial function, particularly evident when glutamate as substrate was studied.

Animals↗
PubMed1984

Favism: a hemolytic disease associated with increased superoxide dismutase and decreased glutathione peroxidase activities in red blood cells.

Red blood cells of favism patients with acute hemolytic crisis have markedly more superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and less glutathione peroxidase (glutathione:hydrogenperoxide oxidoreductase, EC 1.11.1.9) than either normal controls, glucose-6-phosphate dehydrogenase-deficient subjects or favism patients outside hemolytic crisis. This altered value of the two enzyme activities is not due to increased reticulocyte content of blood. The electrophoretic triplet pattern of superoxide dismutase is also changed, with significant increase of the most positively charged band. Similar modifications of the two enzyme activities are observed after treatment of normal red blood cells with high concentrations of divicine and ascorbate, which are redox compounds that are contained in fava seeds. This treatment produces no hemolysis, but leads to hemolysis if the treated cells are resuspended in the homologous plasma. These results suggest a possible role of active oxygen species in the development of favism.

Ascorbic Acid↗
PubMed1984

The effects of hypolipidemic agents derived from procetofenic acid on the activity of superoxide dismutase and glutathione peroxidase and on malonyl dialdehyde production of rat liver.

Male and female rats were treated with hypolipidemic agents derived from procetofenic acid, namely fenofibrate ( procetofene ), cholestyrammonium alpha-(4-p-chlorobenzoyl-phenoxy)-isobutyrate (Alfa-1081) and alpha-(4-p-chlorobenzoyl-phenoxy)-isobutyryl-taurine (35/ipo). A marked decrease of liver superoxide dismutase and glutathione peroxidase was observed in the male rats treated with fenofibrate. In this sample a significant increase of malonyl dialdehyde was also detected when the liver homogenates were subjected to a test of lipid peroxidation induced by active oxygen species. Alfa-1081 and 35/ipo produced no substantial changes of superoxide dismutase and glutathione peroxidase and no significant increase of peroxidation products. These results, while providing an in vivo evidence for the role of superoxide dismutase and glutathione peroxidase as antioxidant enzymes, indicate that hypolipidemic agents can affect also enzymes not bound to membranes as they do with peroxisomal enzymes. The side effect presented here may be harmful, since it can lead to an augmented risk of lipid peroxidation in tissues. It is, however, clear that also within the same class of hypolipidemic drugs the effect is not always present. Peroxidative damage should therefore be considered as a key parameter in the characterization of hypolipidemic agents.

Animals↗
PubMed1983

Multiple electrophoretic variants of Cu, Zn superoxide dismutase as expression of the enzyme aging. Effects of H2O2, ascorbate and metal ions.

Multiple electrophoretic bands, with RF identical to the natural molecular variants, are produced by treatment of purified Cu, Zn Superoxide dismutase with either H2O2 or ascorbate plus Fe(III) EDTA. The ascorbate reaction is also due to H2O2 since it is inhibited by catalase. However while H2O2 inactivates the enzyme, the electromorphs produced by ascorbate-Fe(III) EDTA have only slightly less activity than the native enzyme and this property parallels the natural situation. It is concluded that oxidative aging can be responsible for the multiple molecular variants of the natural enzyme, under conditions where the oxidant attack is preferentially directed to amino acid side chains outside the active site. Such conditions may occur when a metal ion coordinated to the protein surface undergoes a redox cycle with biological reductants, like ascorbate.

Ascorbic Acid↗
PubMed1983

Reduced anion binding and anion inhibition in Cu, Zn superoxide dismutase chemically modified at lysines without alteration of the rhombic distortion of the copper site.

The spectroscopic binding constant (visible absorption and EPR spectra) and the catalytic inhibition constant of N-3 and CN- were measured for bovine Cu, Zn superoxide dismutase chemically modified at all lysines by either succinylation or carbamoylation. These modifications partially inactivate the enzyme (10% and 50% residual activity respectively) but leave the native rhombic geometry of the copper site unaffected. It could thus be shown that the observed reduction of anion affinity of the lysines-modified proteins is related to the decreased positive charge of the protein.

Animals↗
PubMed1983

A comparative study of bovine, porcine and yeast superoxide dismutases.

The Cu,Zn superoxide dismutases from bovine and porcine erythrocytes and from yeast have been investigated with the aim to identify structural differences in relation to possible functional variability in this highly homologous class of protein. The isoelectric points of the bovine, porcine and yeast proteins were found to be 4.8, 5.8 and 4.5 respectively. According to these values the net protein charge, as evaluated by gel electrophoresis, varied more significantly for the porcine protein than for the other two proteins tested. The catalytic constants were found to be higher at pH = 7.6 than at pH 10.0 for all the three enzymes. This relative increase was much more pronounced in the case of the porcine enzyme. The KM value at pH = 10.0 was also significantly higher for the porcine enzyme. Since the spectroscopic properties of the active sites were identical for the three proteins, these results point to modulation effects by positively charged amino acid residues on the superoxide dismutase activity of these proteins, in a way that the resultant net charge of the protein seems to be as important as specific residues.

Animals↗
PubMed1982

Succinylated copper, zinc superoxide dismutase. A novel approach to the problem of active subunits.

Bovine erythrocyte superoxide dismutase (BESOD) has been extensively succinylated with succinic anhydride. Succinylated BESOD has an identical electron paramagnetic resonance (EPR) spectrum but only 10% as much activity as the native enzyme, showing that an increase of the negative charge of the protein surface lowers the activity without alteration of the active site structure. On the other hand, sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel electrophoresis indicates that interaction between subunits is strongly weakened by succinylation. NaDodSO4 has no effect on either the activity or EPR spectrum of the protein. BESOD was immobilized by coupling to a Sepharose matrix with no alteration of the EPR spectrum. Succinylation of the immobilized protein led to detachment from the gel of approximately 50% of the molecules, as estimated by parallel EPR measurements of the gel and activity determinations on the eluate. It is concluded the succinylation leads to dissociation of BESOD into nondenatured subunits, having lower activity than the native protein possibly because of charge effects on the enzyme-O2-interaction.

Animals↗