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Biomedical subjects

M Battino

Publications and source records attributed to M Battino.

At least 19 recordsLinked to original sources

In vitro antioxidant activities of antioxidant-enriched toothpastes.

Several forms of periodontal diseases (PD) are often associated with modified phagocytosing leukocytes and contemporary free radical production. Host antioxidant defenses could benefit from toothpastes used as adjuncts to counteract plaque-associated bacteria. The aim of the present study was to determine possible antioxidant activity (AA) of 12 differently antioxidant-enriched toothpastes, regardless of their efficacy as antimicrobial agents. Toothpastes were enriched alternatively with sodium ascorbyl phosphate, alpha-tocopherol acetate, pycnogenol, allantoin and methyl salycilate or a mixture of these. AA was tested in a cell-free system with a ABTS-decolorization assay improved by means of a flow injection analysis device. Comet assay, using NCTC 2544 keratinocytes, was performed to test if it was possible to identify any protection against in vitro DNA fragmentation provoked by a challenge with H(2)O(2) in cultures pre-incubated with toothpaste extracts. Only toothpastes containing sodium ascorbyl phosphate displayed clear AA with I(50) values ranging between 50 and 80 mg of toothpaste/ml water. COMET analysis of cells challenged with H(2)O(2) in presence of toothpaste extracts revealed a limited protection exerted by sodium ascorbyl phosphate. The results described herein indicate that toothpastes containing sodium ascorbyl phosphate possess AA. All the data were obtained in systems in vitro and the demonstration of in vivo AA is desirable. These findings could be useful in the treatment and maintenance of some forms of PD and should be considered when arranging new toothpaste formulations.

Antioxidants↗

International conference on the healthy effect of virgin olive oil.

1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.

Aging↗

Immunohistochemical analysis of soft tissues in implants with healthy and peri-implantitis condition, and aggressive periodontitis.

Today, implant-supported prostheses are widely accepted as a reliable treatment modality, but failures in longitudinal studies have been shown. In some cases, peri-implantitis with a progressive periodontal bone loss takes place, and mechanical or load factors and biological or plaque-induced lesions have been claimed as main etiologic factors. We compared five cases of peri-implantitis, with five cases of healthy peri-implant tissues and five cases of aggressive periodontitis in order to give new findings on the osseointegration loss process. Biopsy specimens from the peri-implant tissues including oral (O), sulcular, and junctional epithelium and the underlying and supracrestal connective tissue, were taken in all cases for histological and immunohistochemical analysis. T lymphocytes were the most prominent cell in the peri-implantitis (PG) and aggressive periodontitis (AG) groups, but not in the peri-implant healthy group (HG). CD1a-positive cells (Langerhans and immature dendritic cells) were observed more frequently in the O than in the sulcular-junctional (S-J) epithelium: they were located in the basal and parabasal layers, without any differences between the three groups. Vascular proliferation analysed by immunoreactivity for CD34, Factor VIII, and vascular endothelial growth factor was more prominent in the PG comparing with HG and AG in the S-J area. Apoptosis, analysed by bcl2 and p53 immunoreactivity, was similar in the three groups. In conclusion, we suggest that the osseointegration loss process is due to an inflammatory process similar to that observed in aggressive periodontitis according to the number of T lymphocytes, but not to the vascular proliferation.

Adolescent↗

Coenzyme Q differentially modulates phospholipid hydroperoxide glutathione peroxidase gene expression and free radicals production in malignant and non-malignant prostate cells.

The aim of this study was to investigate the role of coenzyme Q on the mRNA abundance of PHGPx and the reactive oxygen species (ROS) production in two different cell lines from human prostate, a line of non cancer cells (PNT2) and a line of cancer cells (PC3). Results showed that malignant cells markedly differ in their response to coenzyme Q compared to non-malignant cells, with no changes in PHGPx expression and greater ROS production. Furthermore coenzyme Q supplementation significantly lowered cell growth of the PC3 cancer line without affecting the PNT2. If these results are confirmed with additional experiments, it could represent a novel and interesting approach on the biomedical use of coenzyme Q10 in cancer therapy.

Cell Line↗

Coenzyme Q, Vitamin E and Apo-E alleles in Alzheimer Disease.

Neurodegenerative Diseases represent the most common cause of Dementia, about 5-10% of the population aged above 65 years and about 30% above 80 years. A study about Apo-E alleles, Coenzyme Q and Vitamins E as biological indicators was performed in plasma samples of patients aged from 30 to 85 years, affected by Neurodegenerative Diseases. The results were compared with control subjects of approximately the same ages as the reference group. A frequency of 21.7% of epsilon4 allele in control group was estimated, against 15.8% observed in patients. The frequency of epsilon2 and epsilon3 alleles was 13.0% and 65.2% in the control group against 10.5% and 73.7% in patients. No significant differences were observed between the frequency of epsilon3/epsilon3 genotype and epsilon3/epsilon4 genotype in the control group compared to patients' group. The frequencies observed in epsilon2/epsilon3 genotype groups were 8.7% vs 15.8% and of e2/e4 genotype 17.4% vs 5.3%. The epsilon2/epsilon2 and epsilon4/epsilon4 genotypes were not identified in any groups. Plasma CoQ10 concentrations were similar in patient and control groups and no differences were found even taking into account the distribution of male and female subjects in the two groups. Also, vitamin E did not provide evidence of any differences between groups and the analysis among sexes revealed that again vitamin E concentrations were similar in between subgroups.

Aged↗

Coenzyme Q10, antioxidant status and ApoE isoforms.

The aim of this study was to inquire the antioxidant status in plasma and lipoproteins isolated from normal subjects possessing different ApoE genotypes. For this purpose we investigated blood samples from 106 healthy blood donors: the distribution of ApoE alleles (E2/E2 = 0.9%, E2/E3 = 10.4%, E2/E4 = 2.8%, E3/E3 = 71.7%, E3/E4 = 12.3% and E4/E4 1.9% with 1, 11, 3, 76, 13, and 2 subjects respectively for each genotype) was in agreement with previous data. Almost no differences were found in the concentrations of both coenzyme Q10 (CoQ10) and vitamin E for the different genotypes. Concentration of CoQ10 in isolated lipoproteins was also similar, in the different genotypes, when referred to cholesterol; CoQ10 in LDL was higher for the E3/E3 subjects when referred to protein. Neither CoQ10 nor vitamin E correlated with paraoxonase (PON) activity or cholesteryl-ester hydroperoxides (CHP). Furthermore, there was no correlation between the same lipophilic antioxidants and CHP levels. The only E2 homozygous subject found had high levels of PON and low levels of CHP; the two E4/E4 subjects had low PON activity together with low levels of CHP.

Alleles↗

Ultrastructure of the gingiva in cardiac patients treated with or without calcium channel blockers.

OBJECTIVES: In the last few years, several studies have suggested that periodontal diseases are related to the development of atherosclerosis and its complications. Our objective was to study the ultrastructural morphology of the gingiva from cardiac patients, some of whom were treated and some not with calcium channel blockers compared to a control group. MATERIAL AND METHODS: Fifty-five patients were studied and grouped in the following way: (a) healthy group (HG) (n=12) healthy patients with at least two pockets between 3 and 5 mm; (b) cardiac group (CG) (n=12) patients with cardiac disease untreated with calcium channel blockers; (c) diltiazem group (DG) (n=13) cardiac patients treated with diltiazem; (d) nifedipine group (NG) (n=18) cardiac patients treated with nifedipine. RESULTS: Ultrastructural studies in the CG showed inflammatory cells, collagen fibers disruption and a more extended morphologically compromised fibroblast mitochondria. Morphometric studies in CG showed mitochondria that were impaired in number but increased in volume, suggesting metabolic cell suffering. In DG and NG, morphometric data were similar to HG. The presence of myofibroblasts and collagen neosynthesis was detected in DG and NG. CONCLUSIONS: Our data showed differences in the ultrastructure of the gingival fibroblasts between the studied groups; the DG and NG showed features that could be interpreted as an attempt to restore the cellular metabolic function.

Calcium Channel Blockers↗

The antioxidant capacity of saliva.

BACKGROUND/AIMS: Saliva, a heterogeneous fluid comprising proteins, glycoproteins, electrolytes, small organic molecules and compounds transported from the blood, constantly bathes the teeth and oral mucosa. It acts as a cleansing solution, an ion reservoir, a lubricant and a buffer. In addition to its other host-protective properties, saliva could constitute a first line of defence against free radical-mediated oxidative stress, since the process of mastication and digestion of ingested foods promotes a variety of reactions, including lipid peroxidation. Moreover, during gingival inflammation, gingival crevicular fluid flow increases the change of saliva composition with products from the inflammatory response; this, in turn, could have some rôle in controlling and/or modulating oxidative damages in the oral cavity. This is the reason why the antioxidant capacity of saliva has led to increasing interest, and the development of techniques suitable for saliva antioxidant evaluation. MATERIALS AND METHODS: Here, we review the current peer-reviewed literature concerning the nature and characteristics of free radicals, reactive oxygen species, oxidants, pro-oxidants and antioxidants in saliva, especially pro-oxidant and antioxidant features, as well as current methods for assessing the antioxidant capacity of saliva. RESULTS AND CONCLUSIONS: In the last decade, several methods have been developed for assaying the antioxidant activity of saliva, indicating an increasing interest of researchers and clinicians. Unfortunately, systematic studies of saliva are still lacking, even in healthy populations.

Antioxidants↗

Dietary fat type and regular exercise affect mitochondrial composition and function depending on specific tissue in the rat.

Physical exercise and fatty acids have been studied in relation to mitochondrial composition and function in rat liver, heart, and skeletal muscle. Male rats were divided into two groups according to dietary fat type (virgin olive and sunflower oils). One-half of the animals from each group were subjected to a submaximal exercise for 8 weeks; the other half acted as sedentary controls. Coenzyme Q, cytochromes b, c + c1, a + a3 concentrations, and the activity of cytochrome c oxidase were determined. Regular exercise increased (P < 0.05) the concentration of the above-mentioned elements and the activity of the cytochrome c oxidase by roughly 50% in liver and skeletal muscle. In contrast, physical exercise decreased (P < 0.05) cytochrome c oxidase activity in the heart (in micromol/min/g, from 8.4+/-0.1 to 4.9+/-0.1 in virgin olive oil group and from 9.7+/-0.1 to 6.7+/-0.2 in sunflower oil animals). Dietary fat type raised the levels of coenzyme Q, cytochromes, and cytochrome c oxidase activity in skeletal muscle (P < 0.05) among the rats fed sunflower oil. In conclusion, dietary fat type, regular exercise, and the specific tissue modulate composition and function of rat mitochondria.

Animals↗

Coenzymes Q9 and Q10, vitamin E and peroxidation in rat synaptic and non-synaptic occipital cerebral cortex mitochondria during ageing.

Great attention has been devoted both to ageing phenomena at the mitochondrial level and to the antioxidant status of membrane structures. These kinds of investigations are difficult to perform in the brain because of its heterogeneity. It is known that synaptic heavy mitochondria (HM) may represent an aged mitochondrial population characterized by a partial impairment of their typical mitochondrial function. We arranged a novel system requiring no extraction procedure, very limited handling of the samples and their direct injection into the HPLC apparatus, to carry out, for the first time, a systematic and concomitant determination of vitamin E, Coenzyme Q9 (CoQ9) and Coenzyme Q10 (CoQ10) contents in rat brain mitochondria. The trends found for CoQ9 and CoQ10 levels in synaptic and non-synaptic occipital cerebral cortex mitochondria during rat ageing are consistent with previous data. Hydroperoxides (HP) differed with age and it was confirmed that in the HM fraction the summation of contributions results in an oxidatively jeopardized subpopulation. We found that vitamin E seems to increase with age, at least in non-synaptic free (FM) and synaptic light (LM) mitochondria, while it was inclined to remain substantially constant in HM.

Age Factors↗

Total antioxidant capacity and nuclear DNA damage in keratinocytes after exposure to H2O2.

Studies of oxidative stress have classically been performed by analyzing specific, single antioxidants. In this study, susceptibility to oxidative stress in the human keratinocyte cell line NCTC2544 exposed to hydrogen peroxide (H2O2) was measured by the TOSC (total oxyradical scavenging capacity) assay, which discriminates between the antioxidant capacity toward peroxyl radicals and hydroxyl radical. The generation of H2O2-induced DNA damage, total antioxidant capacity and levels of antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase, glutathione S-transferase, glutathione peroxidase) were studied. Exposure to H2O2-induced DNA damage that was gradually restored while a significant reduction in cellular TOSC values was obtained independently of stressor concentrations and the degree of DNA repair. Whereas TOSC values and cell resistance to H2O2 showed a good relationship, the extent of DNA damage is independent from cellular total antioxidant capacity. Indeed, maximum DNA damage and cell mortality were observed in the first 4 h, whereas TOSC remained persistently low until 48 h. Catalase levels were significantly lower in exposed cells after 24 and 48 h. Keratinocytes exposed after 48 h to a second H2O2 treatment exhibited massive cell death. A possible linkage was observed between TOSC values and NCTC2544 resistance to H2O2 challenge. The TOSC assay appears to be a useful tool for evaluating cellular resistance to oxidative stress.

Antioxidants↗

Elevated hydroperoxide levels and antioxidant patterns in Papillon-Lefèvre syndrome.

BACKGROUND: Since it has been found that reactive oxygen species seem to be involved in the pathogenesis of both periodontitis and hyperkeratotic syndromes, we studied a group of patients belonging to 3 generations of a family with different degrees of severity of Papillon-Lefèvre syndrome (PLS) to ascertain whether altered concentrations of the most important hydrophobic and hydrophilic plasma antioxidants as well as products of oxidative damage are present in PLS. METHODS: Coenzyme Q (CoQ), vitamin E, glutathione (GSH), and uric acid were evaluated by high-performance liquid chromatography (HPLC) (supplied with electrochemical detector) techniques and hydroperoxides by a spectrophotometric method. RESULTS: GSH and uric acid were in the range of reference values; CoQ was very low in both the child of the third generation and his mother, and these 2 subjects had the highest hydroperoxide levels. The child also had extremely low values of vitamin E. In general, all family members showed abnormally high hydroperoxide levels, with the exception of those members who are phenotypically healthy. CONCLUSIONS: Since the subjects with the lowest hydroperoxide contents are phenotypically healthy, whereas the affected individuals presented lower antioxidant levels and very high hydroperoxide concentrations, it has been suggested that a specific antioxidant therapy could be a promising approach in treating some PLS subjects. Moreover, unexpected manifestations of heterozygosity in the child of the third generation were also detected.

Adult↗

Biochemical changes in transplanted rat liver stored in University of Wisconsin and Euro-Collins solutions.

BACKGROUND: Liver ischemia/reperfusion injury is a severe problem in transplantation, and preservation solutions could be critical for liver viability. The aim of our study was to evaluate the cytosolic and mitochondrial glutathione levels, the glyoxalase II activity, and the mitochondrial hydroperoxide contents of livers stored in different preservation solutions for 7 or 24 h and after transplantation. MATERIALS AND METHODS: Orthotopic liver transplantation was performed without reconstruction of the hepatic artery. The livers were stored at 4 degrees C for 7 or 24 h in University of Wisconsin or Euro-Collins solutions. Portions of livers before and after transplantation were homogenized and mitochondria isolated. RESULTS: Cytosolic glutathione levels were decreased in all stored livers and after transplantation. In livers stored with University of Wisconsin solution, mitochondrial glutathione was unchanged during cold storage and no significant decrease has been found after reperfusion, whereas in livers stored in Euro-Collins solution, mitochondrial glutathione was decreased and a further significant decrease was found 30 min after reperfusion. Mitochondrial hydroperoxides were higher in livers stored in Euro-Collins solution than in University of Wisconsin solution after 30 min of reperfusion. Mitochondrial glyoxalase II did not show any change by reperfusion. CONCLUSION: We have demonstrated that rat liver stored in Euro-Collins solution suffered a severe depletion of mitochondrial GSH and a concomitant increase of hydroperoxides. The data obtained suggested that the livers stored with University of Wisconsin solution were probably less prone to ischemia/reperfusion injury after liver transplantation.

Adenosine↗

Cerebral cortex synaptic heavy mitochondria may represent the oldest synaptic mitochondrial population: biochemical heterogeneity and effects of L-acetylcarnitine.

The microheterogeneous nature of intrasynaptic mitochondria has been demonstrated and is widely accepted. However, evidence is still lacking about the role played by the different intrasynaptic mitochondrial subpopulations. The data obtained support the hypothesis that "heavy" mitochondria could represent old mitochondrial populations: in fact, in addition to the well known impairment of typical mitochondrial functions, they possess the highest levels of hydroperoxides and their fatty acids pattern is completely modified. The qualitative and quantitative fatty acid modifications suffered by these organelles deeply altered their protein/lipid ratio, thus modifying their mode of action. The present work also collects a large body of evidence that a subchronic L-acetylcarnitine treatment in 28 days does not structurally affect both nonsynaptic and intrasynaptic mitochondria of normal rat in a "steady-state" metabolic condition.

Acetylcarnitine↗

Monounsaturated diet lowers LDL oxidisability in type IIb and type IV dyslipidemia without affecting coenzyme Q10 and vitamin E contents.

The purpose of the present study was to evaluate the effects of MUFA vs PUFA enriched diets on the plasma and LDL lipid profile and antioxidant contents in mild hypercholesterolemic and triglyceridemic subjects. The study was divided in two consecutive diet periods. Two groups of 11 dyslipidemic patients each (type IIb and type IV) were recruited and during the first period (lasting four weeks) received a linoleic rich diet while during the following four weeks took an oleate rich diet. Both groups showed no significant changes in cholesterol and TG concentration either in plasma or in LDL. Coenzyme Q10 and vitamin E were also unaffected by the dietary treatments. LDL proneness to be oxidatively modified increased after dietary PUFA administration and markedly decreased following the virgin olive oil enriched diet. In fact, LDL from hypertrigliceridemic subjects on a oleate-enriched diet displayed a 26% (p < 0.05) longer lag-phase in conjugated dienes generation than during linoleate-enriched diet and at recruitment. In hypercholesterolemic subjects similar results were obtained: the lag-phase was 28% longer after MUFA diet that after PUFA diet. No differences were found in the maximum propagation rate and maximum concentration of conjugated dienes among dietary periods and at recruitment. Since we found that the vit. E and CoQ10 levels in plasma and in LDL particles remained unchanged during the course of the study, we may conclude that LDL proneness to undergo oxidative modifications is mainly the result of compositional change due to the enrichment from the different diets of the relative fats.

Cholesterol↗

Olive oil supplemented with vitamin E affects mitochondrial coenzyme Q levels in liver of rats after an oxidative stress induced by adriamycin.

In this study we have evaluated the supplementation of olive oil with vitamin E on coenzyme Q concentration and lipid peroxidation in rat liver mitochondrial membranes. Four groups of rats were fed on virgin olive, olive plus 200 mg/kg of vitamin E or sunflower oils as lipid dietary source. To provoke an oxidative stress rats were administered intraperitoneally 10 mg/kg/day of adriamycin the last two days of the experiment. Animals fed on olive oil plus vitamin E had significantly higher coenzyme Q and vitamin E levels but a lower mitochondrial hydroperoxide concentration than rats fed on olive oil. Retinol levels were not affected, by either different diets or adriamycin treatment. In conclusion, an increase in coenzyme Q and alpha-tocopherol in these membranes can be a basis for protection against oxidation and improvement in antioxidant capacity.

Animals↗

Oxidative stress induced by exercise and dietary fat modulates the coenzyme Q and vitamin A balance between plasma and mitochondria.

Physical exercise induces oxidative stress. Dietary fat modulates lipid composition of plasma and fatty acid profile of mitochondrial membranes. Over 8 wk, two groups of rats were fed virgin olive oil or sunflower oil as the only fat sources. Both groups were divided into 4 subgroups according to exercise: one of sedentary rats and the other three of rats subjected to different exercises on a treadmill. There was a lower concentration of vitamin A and coenzyme Q in the plasma of animals subjected to exercise compared to the sedentary animals. The concentrations of these molecules in liver and skeletal muscle mitochondria of animals exercised until exhaustion were higher than in sedentary animals. This can suggest the existence of a balance between plasma and mitochondrial membrane for these antioxidants as a response to an oxidative attack.

Animals↗

Solid monounsaturated diet lowers LDL unsaturation trait and oxidisability in hypercholesterolemic (type IIb) patients.

Lowering high cholesterol concentration decreases the probability of atherosclerotic-related pathology onset. MUFA and PUFA decrease total plasma and LDL cholesterol but PUFA may increase the susceptibility of LDL to undergo oxidative modifications thus becoming more atherogenetic. Olive oil, the predominant fat source in Mediterranean diet, may combine the advantages of both lowering cholesterol level and decreasing LDL susceptibility to oxidation. We studied the effects of feeding MUFA vs PUFA enriched diet on LDL composition and feature in hypercholesterolemic (IIb) patients. Antioxidant values remained constant during the study while LDL fatty acids composition reflected the dietary intake: MUFA concentration increased 11% whereas PUFA decreased 10% after olive oil diet (p < 0.05). PUFA/MUFA ratio and the unsaturation index were lower at the end of MUFA-enriched diet. The challenge, in vitro, of oleate-enriched LDL with Cu2- yielded to lower lag-phase (p < 0.05) in diene conjugated production; the same LDL gave lower lipid hydroperoxide contents after exposition to AAPH. We conclude that oleate-enriched LDL and with lower PUFA content were more resistant to oxidative modifications, as measured by different peroxidation indexes. This feature acquired with the diet may be an useful tool for lowering LDL oxidation and indirectly their atherogenicity.

Antioxidants↗