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Biomedical subjects

M Tomasetti

Publications and source records attributed to M Tomasetti.

11 recordsLinked to original sources
PubMed2001

Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection.

Generation of free radicals is often associated with the induction and progression of apoptosis. Therefore, antioxidants can prove anti-apoptotic, and can help to elucidate specific apoptotic pathways. Here we studied whether coenzyme Q, present in membranes in reduced (ubiquinol) or oxidised (ubiquinone) forms, can affect apoptosis induced by various stimuli. Exposure of Jurkat cells to alpha-tocopheryl succinate (alpha-TOS), hydrogen peroxide, anti-Fas IgM or TRAIL led to induction of apoptosis. Cell death due to the chemical agents was suppressed in cells enriched with the reduced form of coenzyme Q. However, coenzyme Q did not block cell death induced by the immunological agents. Ubiquinol-10 inhibited reactive oxygen species (ROS) generation in cells exposed to alpha-TOS, and a mitochondrially targeted coenzyme Q analogue also blocked apoptosis triggered by alpha-TOS or hydrogen peroxide. Therefore, it is plausible that ubiquinol-10 protects cells from chemically-induced apoptosis by acting as an antioxidant in mitochondria. Our results also indicate that generation of free radicals may not be a critical step in induction of apoptosis by immunological agents.

Antioxidants↗
PubMed2001

Determination of high-energy phosphate compounds and inorganic phosphate by reversed-phase high-performance liquid chromatography: evaluation of myocardial metabolic status in aerobically perfused and hypoxic mouse heart.

The present paper describes a simple HPLC method designed for measuring high-energy phosphate (HEP) compounds in a single run and inorganic phosphate (Pi) in an other short run under the same HPLC conditions. Inorganic phosphate was estimated by using thymidine phosphorylase (EC 2.4.2.4) which catalyzes a reaction involving inorganic phosphate to produce 2-deoxyribose 1-phosphate and thymine. The thymine/Pi stoichiometry was 1. The method provides a reproducible instrument for evaluating myocardial high-energy metabolism under physiological and pathological conditions.

Animals↗
PubMed2000

Evaluation of ischemia-reperfusion damage during coronary angioplasty. Electrocardiographic assessment and biochemical modifications in blood from the coronary sinus.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) constitutes a clinical model of reperfusion following a short period of ischemia connected to balloon inflation during the procedure. During the procedure some ischemic damage and oxidative injury related to free radical attack might occur. In the present study we investigated the extent of ischemic damage and some biochemical indexes of reperfusion damage in patients undergoing PTCA. METHODS: Twenty-five patients who underwent PTCA because of angiographically detected occlusion of the coronary artery were enrolled. Balloon inflation lasted from 30 to 60 s. ECG changes were monitored throughout the procedure and blood samples were taken from the coronary artery and coronary sinus before balloon inflation, and again from coronary sinus at the peak of ischemia, 2 and 10 min after reperfusion. RESULTS: During PTCA procedure angina pectoris appeared in 62.7% of patients, whereas ST-segment elevation was present in 87% of patients, regressing completely after balloon deflation. Plasma malonyldialdehyde, an index of lipid peroxidation, did not change; coenzyme Q10 (in its oxidized and reduced forms), vitamin E and beta-carotene were also unchanged. Total antioxidant capacity and uric acid decreased upon reperfusion. CONCLUSIONS: Myocardial ischemia occurring during balloon inflation is brief and regresses completely after balloon deflation. Reperfusion following a short period of acute ischemia such as in PTCA does not constitute an oxidative event detectable through a common marker of lipid peroxidation nor does it alter the concentration of lipophilic antioxidants. It only lowers hydrosoluble antioxidants therefore representing a mild oxidative insult.

Aged↗
PubMed1999

Distribution of antioxidants among blood components and lipoproteins: significance of lipids/CoQ10 ratio as a possible marker of increased risk for atherosclerosis.

Total CoQ10 levels were evaluated in whole blood and in plasma obtained from a group of 83 healthy donors. Extraction with light petroleum ether/methanol was more efficient, for whole blood, than the extraction which is often used for plasma and serum, i.e., ethanol hexane. An excellent correlation was present between plasma CoQ10 and whole blood CoQ10. CoQ10 is mainly associated with plasma rather than with cellular components. Positive, significant correlations were found between the LDL-chol/CoQ10 ratio and the total-chol/HDL-chol ratio, which is usually considered a risk factor for atherosclerosis. The proportion of CoQ10 carried by LDL was 58 +/- 10%, while the amount carried by HDL was 26 +/- 8%. In VLDL + IDL CoQ10 was 16 +/- 8%. The content of CoQ10 in single classes of lipoproteins is strictly correlated with CoQ10 plasma concentration. In a parallel study conducted on a population of diabetic patients (one IDDM group and one NIDDM) CoQ10 plasma levels were generally higher compared to the control group, also when normalised to total cholesterol. In particular the LDL fraction showed a CoQ10/chol ratio higher in NIDDM but not in IDDM patients, compared to controls. The CoQ10/triglycerides ratio was lower in NIDDM respect to controls and even lower in IDDM patients.

Aged↗
PubMed1999

Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes.

Ubiquinol-10, the reduced form of coenzyme Q10, is a powerful antioxidant in plasma and lipoproteins. It has been suggested that endogenous ubiquinol-10 also exerts a protective role even towards DNA oxidation mediated by lipid peroxidation. Even though the antioxidant activity of coenzyme Q10 is mainly ascribed to ubiquinol-10, a role for ubiquinone-10 (the oxidized form), has been suggested not only if appropriate reducing systems are present. To investigate whether the concentration of ubiquinol-10 or ubiquinone-10 affects the extent of DNA damage induced by H2O2, we supplemented in vitro human lymphocytes with both forms of coenzyme Q10 and evaluated the DNA strand breaks by Comet assay. The exposure of lymphocytes to 100 microM H2O2 resulted in rapid decrease of cellular ubiquinol-10 content both in ubiquinol-10-enriched and in control cells, whereas alpha-tocopherol and beta-carotene concentration were unchanged. After 30 min from H2O2 exposure, the amount of DNA strand breaks was lower and cells' viability was significantly higher in ubiquinol-10-enriched cells compared with control cells. A similar trend was observed in ubiquinone-10-enriched lymphocytes when compared with control cells. Our experiments suggest that coenzyme Q10 in vitro supplementation enhances DNA resistance towards H2O2-induced oxidation, but it doesn't inhibit directly DNA strand break formation.

Adult↗
PubMed1997

Dietary restriction affects antioxidant levels in rat liver mitochondria during ageing.

Six experimental groups of young (7-month-old) and aged (24-32-month-old) rats, underwent different dietary manipulations (i.e. dietary restriction and/or a vitamin E-depleted diet), and their liver mitochondria were assayed for several antioxidants and peroxidation markers. Glutathione levels were affected both by age and dietary treatment. Coenzyme Q9 and C0Q10 showed the highest levels in the oldest rats where ageing, as well as other oxidative stresses, could induce ubiquinone biosynthesis.

Aging↗
PubMed1997

Oxidation of LDL and their subfractions: kinetic aspects and CoQ10 content.

Coenzyme Q10 in its reduced form, ubiquinol-10, although present in LDL at concentrations considerably lower than that of alpha-tocopherol, exerts a potent antioxidant action in this class of lipoproteins. Previous studies indicated that the content of CoQ10 is the lowest in the densest subfraction of LDL, i.e. LDL3, which is commonly regarded as the most peroxidizable and atherogenic one. These levels were associated with the highest levels of hydroperoxides detectable in the three subclasses. Enrichment of LDL with CoQ10, by means of exogenous supplementation, resulted in a significant increase of CoQ10 in LDL, mainly in LDL3, and in a lower extent of peroxidizability. Spontaneous oxidation of ubiquinol was monitored in plasma and in LDL of unsupplemented and of supplemented subjects and the time-course of oxidation was found considerably slower in CoQ10-enriched LDL. The lagphase of conjugated dienes formation upon induced oxidation was significantly correlated with the absolute content of ubiquinol-10. Distribution of CoQ10 among different classes of plasma lipoproteins was also studied: about 60% of plasma CoQ10 was found associated with LDL.

Administration, Oral↗
PubMed1995

The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions.

The aim of our study was to investigate the relationships between the levels of coenzyme Q10 (CoQ10) and vitamin E and the levels of hydroperoxide in three subfractions of low density lipoproteins (LDL) that were isolated from healthy donors. LDL3, the densest of the three subfractions, has shown statistically significant lower levels of CoQ10 and vitamin E, which were associated with higher hydroperoxide levels when compared with the lighter counterparts. After CoQ10 supplementation, all three LDL subfractions had significantly increased CoQ10 levels. In particular, LDL3 showed the highest CoQ10 increase when compared with LDL1 and LDL2 and was associated with a significant decrease in hydroperoxide level. These results support the hypothesis that the CoQ10 endowment in subfractions of LDL affects their oxidizability, and they have important implications for the treatment of disease.

Adult↗
PubMed1994

Metabolic implications of coenzyme Q10 in red blood cells and plasma lipoproteins.

Plasma coenzyme Q10 (CoQ10) is currently assayed in our laboratory for its well-known diagnostic meaning; in fact plasma CoQ10 levels are inversely related to metabolic demand. Definite levels of CoQ10 are also found in white and red blood cell components, as well as in platelets. Plasma and erythrocyte CoQ10 has a well assessed antioxidant role, which was demonstrated through a series of experiments. Erythrocytes previously enriched with exogenous CoQ10 were found more resistant to a hemolysis induced by a free radical initiator. Several enzymatic activities of erythrocyte ghosts were also protected by different side chain CoQ homologues, both when reduced and, although at a lesser extent, in the oxidized state. CoQ was not effective in preventing metal-catalyzed oxidation of erythrocyte membrane enzymes, and this effect is likely to be due to lack of interaction of CoQ with the metal target. Moreover CoQ was able to protect isolated enzymes and erythrocyte membrane bound enzymes from the inactivating effect of free radicals generated by water sonolysis or radiolysis. As far as plasma lipoproteins are concerned it is well known that LDL isolated from healthy volunteers supplemented with CoQ10 are more resistant to peroxidation induced by an azoinitiator. We started to systematically investigate CoQ10 and vitamin E levels in isolated human LDL and HDL. Both CoQ10 and vitamin E concentrations, referred to protein, were found higher in LDL than in HDL. Susceptibility to exogenously applied peroxidation did not correlate with the endogeneous content of the two antioxidants, possibly on the basis of different lipid content of these lipoproteins.

Alkaline Phosphatase↗
PubMed1994

Chitin-based poly(urea-urethane)s.

Chitins of various origins in DMA-LiCl solution have been reacted with excess 1,6-diisocyanatohexane (three or twelve equivalents per repeating unit) for 4-20 h. The resulting solutions were exposed to water vapor for 2 days and flexible and opaque materials were produced, which upon drying yielded powders whose main characteristics were insolubility in aqueous and organic solvents, remarkable crystallinity, typical infrared spectrum, high N/C ratio (0.287), and a high degree of substitution (0.29). Under the SEM structural features reminiscent of chitin were absent but no thermoplastic behavior was found by differential scanning calorimetry. Chitosan was similarly treated under heterogeneous conditions in anhydrous pyridine, and yielded reaction products with a lower degree of substitution (0.17). With partially hydrolysed chitosan, highly crystalline products were obtained.

Chitin↗