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M Battino

Publications and source records attributed to M Battino.

At least 55 records · Page 3Linked to original sources
PubMed1994

Peroxidative extent and coenzyme Q levels in the rat: influence of physical training and dietary fats.

Sport practice is widely recognized as capable of producing peroxidative damages, even of severe intensity. Dietary manipulations can also modify membrane susceptibility to peroxidation. In previous experiments we found that, while dietary virgin olive oil successfully protects mitochondrial and microsomal membranes from endogenous, xenobiotics-induced peroxidation, dietary polyunsaturated oils lead to increased peroxidative levels. In the latter conditions, cell machinery tries to counteract the structural and functional changes which have occurred, by modulating enzyme activities and concentrations, by increasing biosynthesis of coenzyme Q and by mobilizing cholesterol. In the present study we hypothesized that combining these two aspects could give useful information on the membrane response to peroxidation phenomena that daily occur throughout the lifespan. Rats fed different dietary oils as only fat source underwent a carefully designed training program and were killed at different times following acute or chronic exercise. Results show that peroxidation related to chronic training and to an acute bout of exercise sum up with peroxidative effects induced by dietary factors. The above mentioned phenomena occurred simultaneously with increased tissue levels of coenzyme Q, possibly triggered within a physiological reactive antioxidant strategy.

Aging↗
PubMed1994

Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors.

The biosynthetic pathway of the CoQ polyisoprenoid side chain, starting from acetyl-CoA and proceeding through mevalonate and isopentenylpyrophosphate, is the same as that of cholesterol. We performed this study to evaluate whether vastatins (hypocholesterolemic drugs that inhibit HMG-CoA reductase) modify blood levels of ubiquinone. Thirty-four unrelated outpatients with hypercholesterolemia (IIa phenotype) were treated with 20 mg of simvastatin for a 6-month period (group S) or with 20 mg of simvastatin plus 100 mg CoQ10 (group US). The following parameters were evaluated at time 0, 45, 90, 135 and 180 days: total plasma cholesterol (TC), HDL-cholesterol, LDL-cholesterol (LDL-C), triglycerides (TG), apo A1, apo B and CoQ10 in plasma and platelets. In the S group, there was a marked decrease in TC and LDL-C (from 290.3 mg/dl to 228.7 mg/dl for TC and from 228.7 mg/dl to 167.6 mg/dl for LDL-C) and in plasma CoQ10 levels from 1.08 mg/dl to 0.80 mg/dl. In contrast, in the US group we observed a significant increase of CoQ10 in plasma (from 1.20 to 1.48 mg/dl) while the hypocholesterolemic effect was similar to that observed in the S group. Platelet CoQ10 also decreased in the S group (from 104 to 90 ng/mg) and increased in the US group (from 95 to 145 ng/mg). This study demonstrates that simvastatin lowers both LDL-C and apo B plasma levels together with the plasma and platelet levels of CoQ10, and that CoQ10 therapy prevents both plasma and platelet CoQ10 decrease, without affecting the cholesterol lowering effect of simvastatin.

Apolipoproteins B↗
PubMed1994

The effect of dietary lipid changes on the fatty acid composition and function of liver, heart and brain mitochondria in the rat at different ages.

A correlation between dietary lipids and cellular enzyme activities is a problem that has only been partially addressed by nutritionists. Therefore, changes in the fatty acid composition and the activities of some key metabolic enzymes (ubiquinol-2-cytochrome c reductase (EC 1.10.2.2), cytochrome oxidase (EC 1.9.3.1) and ATPase (EC 3.6.1.3)) in the mitochondria of liver, heart and brain of rats fed on diets differing extensively in their polyunsaturated fatty acid compositions have been investigated. The results showed that fatty acid compositional changes brought about by the dietary differences were associated with extensive changes in the activities of these key enzymes in the mitochondria. The extent of the influence differed considerably with the period over which the diets were fed. The role of dietary lipids to effect changes through the preservation of membrane structural integrity is discussed.

Adenosine Triphosphatases↗
PubMed1994

Susceptibility to in vitro lipid peroxidation of low density lipoproteins and erythrocyte membranes from liver cirrhotic patients.

The aim of the present study was to investigate the susceptibility of low density lipoprotein (LDL) and red blood cell membranes (RCM) from liver cirrhotic patients and control subjects, to the peroxidative stress, induced in vitro by phenylhydrazine. The susceptibility to peroxidation was determined by measuring the formation of the thiobarbituric acid reactive substances (TBARS) after incubation with phenylhydrazine. Moreover the levels of cholesterol (C) and phospholipid (PL) were evaluated in plasma and isolated LDL and RCM. A significant decrease in plasma C, LDL-C and RCM-C content (p < 0.001, p < 0.01 and p < 0.05 respectively) and RCM-PL content (p < 0.01) were found in cirrhotic patients compared to controls. The lower susceptibility to in vitro peroxidation was shown by the TBARS levels significantly lower in LDL and RCM from cirrhotic patients with respect to controls (p < 0.0001 for both of them). Moreover significant positive correlations were found between TBARS-LDL and LDL-C or LDL-PL (r = +0.72, p < 0.0001; r = +0.58, p < 0.001) and between TBARS-RCM and RCM-C (r = +0.35, p < 0.05) or RCM-PL (r = 0.37, p < 0.05) from combined patients and controls. Our data seem to ascribe the lower in vitro peroxidability to the lower levels of plasma lipids.

Adult↗
PubMed1993

Antioxidant effect of coenzyme Q on hydrogen peroxide-activated myoglobin.

In recent years increased attention has been focused on the reduced forms of coenzyme Q as antioxidant compounds inhibiting lipid peroxidation in model systems and in biological membranes, but in spite of extensive experimental evidences the molecular mechanisms responsible for the antioxidant activity of ubiquinones are still debated. Ferrylmyoglobin and/or its free radical form are regarded as powerful oxidizing agents capable of promoting oxidation of essential cellular constituents, particularly cell membranes. Therefore, we investigated the effects of ubiquinol on the formation and survival of ferryl species of myoglobin and on metmyoglobin itself. The addition of a threefold molar excess of hydrogen peroxide to a solution of metmyoglobin induces the rapid formation of a compound with the spectral characteristics of ferrylmyoglobin. The reaction is complete within 4 min, producing up to 76% of ferrylmyoglobin, which remains stable for at least 30 min. The addition of ubiquinol-1 to the same solution provokes a rapid and progressive reduction of ferrylmyoglobin to metmyoglobin and oxymyoglobin. Ubiquinol-1, furthermore, is also capable of protecting metmyoglobin against oxidation when added in the solution before hydrogen peroxide. Ubiquinol-1, indeed, is effective at both limiting the maximal ferrylmyoglobin level attained (59% inhibition) and accomplishing complete removal of the ferryl form (in about 15 min). The results demonstrate that ubiquinol is capable of reducing both ferrylmyoglobin and metmyoglobin to oxymyoglobin, providing a novel antioxidant mechanism for coenzyme Q.

Antioxidants↗
PubMed1992

Improved high-performance liquid chromatographic method for the determination of coenzyme Q10 in plasma.

Coenzyme (Co) Q10 was dissociated from lipoproteins in plasma by treatment with methanol and extraction with n-hexane. Subsequent clean-up on silica gel and C18 solid-phase extraction cartridges with complete recovery (99 +/- 1.2%) produced a clean extract. High-performance liquid chromatographic (HPLC) separation was performed on a C18 reversed-phase column. Three simple, rapid procedures are presented: HPLC with final UV (275 nm) detection, a microanalysis utilizing a three-electrode electrochemical detector and a microanalysis with column-switching HPLC and electrochemical detection. The methods correlate very well with classical ethanol-n-hexane extraction with UV detection. The identity and purity of the Co Q10 peak were investigated and the resulting methods were concluded to be suitable for total plasma Co Q10 determination. The average level in healthy subjects was 0.80 +/- 0.20 mg/l; the minimum detectable Co Q10 plasma level was 0.05 and 0.005 mg/l for UV and electrochemical detection, respectively. The methods were applied to many samples and the plasma Co Q10 reference values for healthy subjects, athletes, hyperthyroid, hypothyroid and hypercholesterolaemic patients are given.

Chromatography, High Pressure Liquid↗
PubMed1992

On coenzyme Q orientation in membranes: a linear dichroism study of ubiquinones in a model bilayer.

A general approach is developed to interpret linear dichroism (LD) spectra of ubiquinones (Qn) in host bilayers. Information is reported in terms of guest-host mutual orientation and localization. The overall orientational anisotropy of guest ubiquinone molecules is described by a basic set of limiting orientation/localization modes. Assignments of the UV transitions of the ubiquinone chromophore were obtained by the liquid crystal-linear dichroism technique and molecular orbital (CNDO/S) calculations. The LD spectra of Qn in the bilayers provided by the lyotropic nematic mesophase exhibited by water solutions of potassium laurate and decanol were interpreted on the basis of the above assignments. The resulting experimental evidence showed a multisite distribution in the host bilayer for the aromatic heads of all the investigated Qn derivatives except Q0. The orientational distribution suggested by the LD spectra fits the solubilization model recently proposed by G. Lenaz [J. Membrane Biol. (1988) 104:193-209] for ubiquinone in lipid membranes. Within this model Qn molecules are located in the midplane and their headgroups oscillate transversally across the membrane. Q0 instead has a single site location, close to the polar bilayer interface. Experimental evidence that the headgroup carbonyls tend to grasp the polar interface of the host bilayer was also obtained. Orientation and location distributions of Qn guest molecules are therefore likely to result from the tendency of their aromatic heads to grasp the polar heads of the host bilayer and from the concurrent tendency of their chains to settle into the hydrocarbon host interior.

Cell Membrane↗
PubMed1992

Coenzyme Q-pool function in glycerol-3-phosphate oxidation in hamster brown adipose tissue mitochondria.

We have investigated the role of the Coenzyme Q pool in glycerol-3-phosphate oxidation in hamster brown adipose tissue mitochondria. Antimycin A and myxothiazol inhibit glycerol-3-phosphate cytochrome c oxidoreductase in a sigmoidal fashion, indicating that CoQ behaves as a homogeneous pool between glycerol-3-phosphate dehydrogenase and complex III. The inhibition of ubiquinol cytochrome c reductase is linear at low concentrations of both inhibitors, indicating that sigmoidicity of antimycin A and myxothiazol inhibition is not a direct property of antimycin A and myxothiazol binding. Glycerol-3-phosphate cytochrome c oxidoreductase is strongly stimulated by added CoQ3, indicating that endogenous CoQ is not saturating. Application of the pool equation for nonsaturating ubiquinone allows calculation of the Km for endogenous CoQ of glycerol-3-phosphate dehydrogenase of 3.14 mM. The results of this investigations reveal that CoQ behaves as a homogeneous pool between glycerol-3-phosphate dehydrogenase and complex III in brown adipose tissue mitochondria; moreover, its concentration is far below saturation for maximal electron transfer activity in comparison with other branches of the respiratory chain connected with the CoQ pool. HPLC analysis revealed a lower amount of CoQ in brown adipose mitochondria (0.752 nmol/mg protein) in comparison with mitochondria from other tissues and the presence of both CoQ9 and CoQ10.

Adipose Tissue, Brown↗
PubMed1992

Mitochondrial and microsomal cholesterol mobilization after oxidative stress induced by adriamycin in rats fed with dietary olive and corn oil.

The influence of three different dietary fats (8%) and of endogenous lipid peroxidation with regard to cholesterol concentrations in liver mitochondria and microsomes and in serum has been investigated in the rat. Although the different diet fat used did not produce any effect on serum cholesterol, it was possible to show that each experimental diet differently influenced the microsomal and mitochondrial levels of cholesterol. The highest mitochondrial and microsomal cholesterol content was found in case of diet supplemented with virgin olive oil and the lowest with rectified olive oil. An endogenous oxidative stress induced by adriamycin was able to produce a clear decrease in microsomal and mitochondrial cholesterol level and a sharp increase in serum concentration in all three groups. However, dietary fats and adriamycin had no effect on the microsomal and mitochondrial membrane viscosity as detected by fluorescence polarization. These results are consistent with the hypothesis that mitochondrial and microsomal cholesterol can exchange with exogenous pools when phospholipid peroxidation occurs.

Animals↗
PubMed1992

Localization and preferred orientations of ubiquinone homologs in model bilayers.

The localization of ubiquinone has been investigated in phospholipid bilayer vesicles in studies of fluorescence quenching of membrane-bound probes by ubiquinone homologs (Qn, where n is the number of the isoprenoid units of the chain). Fluorescence-quenching data obtained by using a set of anthroylstearate probes, having the fluorophore located at different depths, revealed that ubiquinone-3 is located throughout the whole bilayer thickness. From the bimolecular quenching constants in the membrane, lateral diffusion coefficients in two dimensions were calculated to span values of 10(-7)-10(-6) cm2.s-1. This suggests that ubiquinones laterally diffuse in a very fluid environment. On this basis, it is proposed that their translational diffusion in the bilayer takes place in two dimensions, with the quinone ring oscillating between the two bilayer surfaces within a hydrophobic environment not extending beyond the glycerol region. This model implies that the quinonic head is both settled near the polar surface of the bilayer and buried into the host hydrocarbon interior. This two-site distribution was confirmed for all Qn, except Q0, by their linear dichroism spectra in the bilayers provided by disc-like lyotropic nematic liquid crystals. These spectra also provided detailed information on the preferential orientations of the quinonic head of the different derivatives within the two sites. The mechanism by which the localization and orientation of Qn guest molecules inside the host bilayer is modulated by the isoprenoid chain length is discussed on a thermodynamical basis. Being that Qn is expected to be also widely contained in the highly curved cristae of the mitochondrial inner membrane, by using rod-like lyotropic nematic liquid crystals we searched out effects of the curvature of the host bilayer on those Qn distributions. The linear dichroism measurements reveal that Qn guest molecules are no longer obliged to find a partition between two different types of localizations when the host bilayer is highly curved. In this case all Qn, even the longest Q10, were found to stay parallel to the amphiphilic chains with a single site localization of the head near the polar interface. By the same linear dichroism technique, the local ordering of all Qn derivatives was also evaluated. The order parameters were found to be basically the same for all derivatives. This result is justified on the basis of the relaxation, caused by the surface curvature, of the lateral compression of the host chains.

Chemical Phenomena↗
PubMed1992

[Cytochrome oxidase induction following oxidative stress produced by adriamycin in the heart of rats fed olive oil].

Cytochrome oxidase is extremely susceptible to modifications that could occur at membrane level such as, for example, the deep influence that cardiolipin has on its maximal activity. Moreover, even the different ratio of fatty acid species in cardiolipin molecule could affect cytochrome oxidase properties. The influence of dietary fat and of endogenous lipid peroxidation with regard to cytochrome c oxidase activity and cytochrome a+a3 concentrations in mitochondria from rat heart has been investigated. Whilst the endogenous oxidative stress led to increase the peroxidation products, detected by means of hydroperoxides and conjugated dienes determinations, the features of the lipid environment were not affected as shown by fluorescence polarization technique. However, the oxidative stress was able to induce a significant increase of cytochrome a+a3 level even if the phenomenon did not reach the same extent as in the case of previous investigations on rat liver. Moreover, the results vary with the different fat source used and this might indicate a possible involvement of different dietary fats in peroxidation mechanisms. Furthermore the data we have obtained enable us to confirm once more that an induction of the synthesis of cytochrome a+a3 might be related to an enhanced production of peroxides at membrane level.

Animals↗
PubMed1991

Cytochrome oxidase induction after oxidative stress induced by adriamycin in liver of rats fed with dietary olive oil.

The influence of different kinds of dietary fat (8%) and of endogenous lipid peroxidation with regard to cytochrome c oxidase activity and cytochrome a + a3 concentrations in mitochondria from rat liver has been investigated. It was possible to confirm that the dietary fat induced higher phospholipid degradation in mitochondrial membranes; moreover an endogenous oxidative stress induced by adriamycin was able to increase the peroxidative effects. We have found that the peroxidative effects could sometimes induce an apparent enhancement of cytochrome oxidase activity due to a significant increase of cytochrome a + a3 content. This finding lets us suppose that both changes in the lipid environment and some peroxidation damage could occur in the membrane as a consequence of the fat assumed. Furthermore we should suggest that an induction of the synthesis of cytochrome a + a3 might be related to an enhanced production of peroxides at membrane level.

Animals↗
PubMed1991

Changes in mitochondrial and microsomal rat liver coenzyme Q9 and Q10 content induced by dietary fat and endogenous lipid peroxidation.

The influence of different kinds of dietary fat (8%) and of endogenous lipid peroxidation with regard to coenzyme Q9 (CoQ9) and coenzyme Q10 (CoQ10) concentrations in mitochondria and microsomes from rat liver has been investigated by means of an HPLC technique. Although the different diet fats used did not produce any effect on microsomes, it was possible to show that each experimental diet differently influenced the mitochondrial levels of CoQ9 and CoQ10. The highest mitochondrial CoQ content was found in case of a diet supplemented with corn oil. An endogenous oxidative stress induced by adriamycin was able to produce a sharp decrease in mitochondrial CoQ9 levels in the rats to which corn oil was administered. The results suggest that dietary fat ought to be considered when studies concerning CoQ mitochondrial levels are carried out.

Animals↗
PubMed1991

Structural and functional aspects of the respiratory chain of synaptic and nonsynaptic mitochondria derived from selected brain regions.

Studies on brain mitochondria are complicated by the regional, cellular, and subcellular heterogeneity of the central nervous system. This study was performed using synaptic and nonsynaptic mitochondria obtained from cortex, hippocampus, and striatum of male Sprague-Dawley rats (3 months old). Ubiquinone content, detected by HPLC analysis, was about 1.5 nmol/mg protein with an approximate CoQ9/CoQ10 molecular ratio of 2:1. The activities of several respiratory chain complexes were also studied (succinate-cyt. c reductase, NADH-cyt. c reductase, succinate-DCIP, ubiquinol2-cyt. c reductase, and cytochrome oxidase), and generally found to be higher in mitochondria from cortex than from other regions. Study of the activities of some of these enzymes vs. 1/T (Arrhenius plots) showed a straight line with an activation energy between 7 and 10 kcal/mol in all the three areas considered. Only CoQ2H2-cyt. c reductase activity revealed a biphasic temperature dependence. Also anisotropy (as fluorescence polarization) of the hydrophobic probe DPH showed a deviation from linearity; the break points for both enzymatic activity and anisotropy were found at about 23-24 degrees C.

Animals↗
PubMed1990

Changes in hepatic folylpolyglutamate pattern in phenobarbitone-treated rats.

Folate deficiency is a common unpleasant secondary effect of anticonvulsant therapy. In order to contribute to the knowledge of biochemical mechanisms leading to this condition, the effects of two i.p. high doses of phenobarbitone administered to the rat (acute treatment) on the distribution of hepatic folate derivatives have been studied. A significant decrease of unsubstituted tetrahydro- and dihydropteroylpentaglutamates and 5,10-methylenetetrahydropentaglutamates was observed. The hypothesis that a lower availability of NADPH, which is utilized for hydroxylation reactions in phenobarbitone metabolism, may limit folate reduction is proposed.

Animals↗
PubMed1990

Studies on the role of ubiquinone in the control of the mitochondrial respiratory chain.

This study examines the possible role of Coenzyme Q (CoQ, ubiquinone) in the control of mitochondrial electron transfer. The CoQ concentration in mitochondria from different tissues was investigated by HPLC. By analyzing the rates of electron transfer as a function of total CoQ concentration, it was calculated that, at physiological CoQ concentration NADH cytochrome c reductase activity is not saturated. Values for theoretical Vmax could not be reached experimentally for NADH oxidation, because of the limited miscibility of CoQ10 with the phospholipids. On the other hand, it was found that CoQ3 could stimulate alpha-glycerophosphate cytochrome c reductase over three-fold. Electron transfer being a diffusion-coupled process, we have investigated the possibility of its being subjected to diffusion control. A reconstruction study of Complex I and Complex III in liposomes showed that NADH cytochrome c reductase was not affected by changing the average distance between complexes by varying the protein: lipid ratios. The results of a broad investigation on ubiquinol cytochrome c reductase in bovine heart submitochondrial particles indicated that the enzymic rate is not diffusion-controlled by ubiquinol, whereas the interaction of cytochrome c with the enzyme is clearly diffusion-limited.

Adipose Tissue↗
PubMed1990

Coenzyme Q can control the efficiency of oxidative phosphorylation.

Energy of metabolic oxidations is conserved in the form of ATP by the process of oxidative phosphorylation in mitochondria. The possibility to recognize alterations in the efficiency of oxidative phosphorylation in pathological states and to improve this efficiency in order to correct diseases requires knowledge of the mechanisms controlling the rate of ATP synthesis. This task is hampered by uncertainties still existing on the organization and mechanism of the enzymes carrying out oxidative phosphorylation. The authors have collected experimental evidence that coenzyme Q concentration in the mitochondrial membrane phospholipids in physiologically not saturating for maximal electron-transfer rate: in fact the Km of the redox enzymic complexes, using the oxidized and reduced form of coenzyme Q, for these substrates, are in the range of their concentrations in the membrane. The addition of exogenous coenzyme Q enhances the respiratory turnover above the physiological rate but without reaching theoretical Vmax, owing to the limited miscibility of ubiquinones with the membrane phospholipids. On the contrary, a decrease of ubiquinone content in the membrane lowers electron-transfer activity in a reversible fashion. Taking account that the rate of lateral coenzyme Q diffusion in the membrane does not appear to control electron transfer, it is suggested that only ubiquinone concentration affects the efficiency of oxidative phosphorylation, with interesting pathological and pharmacological implications.

Animals↗