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1.
Andrologia ; 46(7): 805-7, 2014 Sep.
Article in English | MEDLINE | ID: mdl-23964789

ABSTRACT

Many conditions associated with male infertility are inducers of oxidative stress, including varicocele. Antioxidants, such as coenzyme Q10, may be useful in this case. To evaluate the antioxidant capacity of seminal plasma of infertile men with varicocele before and after an oral supplementation with coenzyme Q10 , 38 patients were recruited from a pilot clinical trial. A standard semen analysis was also performed at baseline and 3 months after an oral supplementation with exogenous coenzyme Q10 100 mg per die. Seminal plasma antioxidant capacity was measured using a spectroscopic method. Coenzyme Q10 therapy improved semen parameters and antioxidant status. This study highlights the importance of oxidative stress in the pathogenesis of male infertility, namely in varicocele, and strengthens the possibility of the usefulness of the antioxidant therapy.


Subject(s)
Infertility, Male/drug therapy , Ubiquinone/analogs & derivatives , Varicocele/complications , Dietary Supplements , Humans , Infertility, Male/etiology , Male , Pilot Projects , Ubiquinone/administration & dosage
2.
Pituitary ; 13(2): 138-45, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20012698

ABSTRACT

The role of adrenal steroids in antioxidant regulation is not known. Previously, we demonstrated some Coenzyme Q(10) (CoQ(10)) alterations in pituitary diseases, which can induce complex pictures due to alterations of different endocrine axes. Therefore we determined CoQ(10) and Total Antioxidant Capacity (TAC) in pituitary-dependent adrenal diseases: 6 subjects with ACTH-dependent adrenal hyperplasia (AH); 19 with secondary isolated hypoadrenalism (IH), 19 with associated hypothyroidism (multiple pituitary deficiencies, MPH). CoQ(10) was assayed by HPLC; TAC by the system metmyoglobin-H(2)O(2), which, interacting with the chromogenous 2,2(I)-azinobis-(3-ethylbenzothiazoline-6-sulphonate), generates a spectroscopically revealed radical compound after a latency time (Lag) proportional to the antioxidant content. CoQ(10) levels were significantly lower in IH than AH and MPH, with a similar trend when adjusted for cholesterol. Also TAC was lower in IH than in AH and MPH, suggesting that adrenal hormones can influence antioxidants. However, since thyroid hormones modulate CoQ(10) levels and metabolism, when thyroid deficiency coexists it seems to play a prevalent influence.


Subject(s)
Antioxidants/metabolism , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/pathology , Adrenal Hyperplasia, Congenital/metabolism , Adrenal Insufficiency/metabolism , Chromatography, High Pressure Liquid , Humans , Hypothyroidism/metabolism , Ubiquinone/metabolism
3.
J Endocrinol Invest ; 33(6): 422-33, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20631494

ABSTRACT

Oxidative stress, a condition defined as unbalancing between production of free radicals and antioxidant defenses, is an important pathogenetic mechanism in different diseases. Despite the abundant literature, many aspects of hormone role in regulating antioxidant synthesis and activity still remain obscure. Therefore, we reviewed experimental data, in vivo and in vitro, about the effects of the different pituitary- dependent axes on antioxidant levels, trying to give a broad view from hormones which also have antioxidant properties to the classic antioxidants, from the lipophilic antioxidant Coenzyme Q10, strictly related to thyroid function, to total antioxidant capacity, a measure of non-protein non-enzymatic antioxidants in serum and other biological fluids. Taken together, these data underline the importance of oxidative stress in various pituitary-dependent disorders, suggesting a possible clinical usefulness of antioxidant molecules.


Subject(s)
Antioxidants/physiology , Oxidative Stress/physiology , Pituitary Gland/physiology , Animals , Estradiol/physiology , Female , Gonads/physiology , Growth Hormone/physiology , Humans , Male , Pituitary-Adrenal System/physiology , Prolactin/physiology , Testosterone/physiology , Thyroid Gland/physiology , Ubiquinone/physiology
4.
J Endocrinol Invest ; 32(7): 626-32, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19509475

ABSTRACT

We had previously demonstrated that Coenzyme Q10 [(CoQ10) also commonly called ubiquinone] is present in well-measurable levels in human seminal fluid, where it probably exerts important metabolic and antioxidant functions; seminal CoQ10 concentrations show a direct correlation with seminal parameters (count and motility). Alterations of CoQ10 content were also shown in conditions associated with male infertility, such as asthenozoospermia and varicocele (VAR). The physiological role of this molecule was further clarified by inquiring into its variations in concentrations induced by different medical or surgical procedures used in male infertility treatment. We therefore evaluated CoQ10 concentration and distribution between seminal plasma and spermatozoa in VAR, before and after surgical treatment, and in infertile patients after recombinant human FSH therapy. The effect of CoQ10 on sperm motility and function had been addressed only through some in vitro experiments. In two distinct studies conducted by our group, 22 and 60 patients affected by idiopathic asthenozoospermia were enrolled, respectively. CoQ10 and its reduced form, ubiquinol, increased significantly both in seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, at baseline and after treatment, of seminal plasma or intracellular CoQ10, ubiquinol levels and kinetic parameters was found in the treated group. Patients with lower baseline value of motility and CoQ10 levels had a statistically significant higher probability to be responders to the treatment. In conclusion, the exogenous administration of CoQ10 increases both ubiquinone and ubiquinol levels in semen and can be effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.


Subject(s)
Infertility, Male , Ubiquinone/analogs & derivatives , Vitamins , Animals , Asthenozoospermia/enzymology , Double-Blind Method , Humans , Infertility, Male/drug therapy , Infertility, Male/enzymology , Male , Oxidation-Reduction , Randomized Controlled Trials as Topic , Semen/enzymology , Sperm Motility/physiology , Spermatozoa/enzymology , Ubiquinone/metabolism , Ubiquinone/therapeutic use , Vitamins/metabolism , Vitamins/therapeutic use
5.
Free Radic Biol Med ; 45(3): 345-54, 2008 Aug 01.
Article in English | MEDLINE | ID: mdl-18485919

ABSTRACT

This paper reports on the synthesis and properties of a new UV-absorber (OC-NO) based on the most popular UV filter worldwide, ethylhexyl methoxycinnamate (OMC) in which the methoxy group has been replaced with a pyrrolidine nitroxide bearing antioxidant activity. This sunscreen active has therefore both UV-absorbing and antioxidant properties which could ideally address both the UV-B and UV-A skin photo-damage. For broad-spectrum coverage, the combinations of OC-NO with two commonly used UV-A absorbers (BMDBM and DHHB) were also studied. The results obtained reveal that OC-NO: (a) is as photostable as OMC after UV-A exposure; (b) acts as free radical scavenger as demonstrated by EPR and chemical studies; (c) reduces UV-A and UV-A+BMDBM induced lipid peroxidation in liposomes and cells, measured as reduced TBARS levels and increased C11-BODIPY red fluorescence, respectively; (d) has comparable antioxidant activity to that of vitamin E and BHT commonly used in skin care formulations; (e) is non-cytotoxic to human skin fibroblasts as assessed with the MTT assay when exposed to increasing doses of UV-A; and (f) OC-NO+DHHB is a promising, photostable broad spectrum UV-filter combination that concomitantly reduces UV-induced free radical damage. These results suggest that nitroxide/antioxidant-based UV-absorbers may pave the way for the utilization of 'multi-active' ingredients in sunscreens thereby reducing the number of ingredients in these formulations.


Subject(s)
Cinnamates/chemistry , Cyclic N-Oxides/chemistry , Radiation Protection/methods , Sunscreening Agents/chemical synthesis , Antioxidants/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacology , Cinnamates/pharmacology , Fibroblasts/drug effects , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/pharmacology , Humans , Lipid Peroxidation/drug effects , Sunburn/prevention & control , Sunscreening Agents/chemistry , Sunscreening Agents/pharmacology
6.
Biofactors ; 32(1-4): 161-7, 2008.
Article in English | MEDLINE | ID: mdl-19096112

ABSTRACT

Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with mental retardation and Alzheimer-like dementia, characteristic change of the individual's phenotype and premature ageing. Oxidative stress is known to play a major role in this pathology since a gene dose effect leads to elevated ratio of superoxide dismutase to catalase/glutathione peroxidase compared to controls in all age categories suggesting that oxidative imbalance contributes to the clinical manifestation of DS. Hyperuricemia is another feature of DS that has an interesting relationship with oxidative stress since uric acid represents an important free radical scavenger. However its formation is connected to the conversion of Xanthine dehydrogenase (XDH) to Xanthine oxidase (XO) which leads to concomitant production of free radicals. Here we report that plasma samples from DS patients in pediatric age, despite an increased total antioxidant capacity, largely due to elevated Uric acid content (UA), present significantly elevated markers of oxidative damage such as increased allantoin levels. Moreover DS plasma samples do not differ from healthy control ones in terms of Coenzyme Q10 and susceptibility to peroxidative stimuli. On the contrary, lymphocyte and platelet CoQ10 content was significantly lower in DS patients, a fact that might underlie oxidative imbalance at a cellular level.


Subject(s)
Down Syndrome/metabolism , Oxidative Stress/drug effects , Ubiquinone/analogs & derivatives , Allantoin/blood , Child , Child, Preschool , Humans , Ubiquinone/metabolism , Uric Acid/blood
7.
Biochim Biophys Acta ; 1100(3): 235-41, 1992 Jun 19.
Article in English | MEDLINE | ID: mdl-1351746

ABSTRACT

Ubiquinol-1 in aerated aqueous solution inactivates several enzymes--alanine aminotransferase, alkaline phosphatase, Na+/K(+)-ATPase, creatine kinase and glutamine synthetase--but not isocitrate dehydrogenase and malate dehydrogenase. Ubiquinone-1 and/or H2O2 do not affect the activity of alkaline phosphatase and glutamine synthetase chosen as model enzymes. Dioxygen and transition metal ions, even if in trace amounts, are essential for the enzyme inactivation, which indeed does not occur under argon atmosphere or in the presence of metal chelators. Supplementation with redox-active metal ions (Fe3+ or Cu2+), moreover, potentiates alkaline phosphatase inactivation. Since catalase and peroxidase protect while superoxide dismutase does not, hydrogen peroxide rather than superoxide anion seems to be involved in the inactivation mechanism through which oxygen active species (hydroxyl radical or any other equivalent species) are produced via a modified Haber-Weiss cycle, triggered by metal-catalyzed oxidation of ubiquinol-1. The lack of efficiency of radical scavengers and the almost complete protection afforded by enzyme substrates and metal cofactors indicate a 'site-specific' radical attack as responsible for the oxidative damage.


Subject(s)
Enzyme Inhibitors/pharmacology , Metals/pharmacology , Ubiquinone/metabolism , Alanine Transaminase/antagonists & inhibitors , Alanine Transaminase/metabolism , Alkaline Phosphatase/antagonists & inhibitors , Alkaline Phosphatase/metabolism , Animals , Catalysis , Cations , Cattle , Creatine Kinase/antagonists & inhibitors , Creatine Kinase/metabolism , Free Radical Scavengers , Glutamate-Ammonia Ligase/antagonists & inhibitors , Glutamate-Ammonia Ligase/metabolism , Hydrogen-Ion Concentration , Oxidation-Reduction , Pentetic Acid/pharmacology , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Sodium-Potassium-Exchanging ATPase/metabolism , Substrate Specificity , Swine
8.
Biofactors ; 25(1-4): 165-74, 2005.
Article in English | MEDLINE | ID: mdl-16873942

ABSTRACT

This review is focused upon the role of coenzyme Q(10) in male infertility in the light of a broader issue of oxidative damage and antioxidant defence in sperm cells and seminal plasma. Reactive oxygen species play a key pathogenetic role in male infertility besides having a well-recognized physiological function. The deep involvement of coenzyme Q(10) in mitochondrial bioenergetics and its antioxidant properties are at the basis of its role in seminal fluid. Following the early studies addressing its presence in sperm cells and seminal plasma, the relative distribution of the quinone between these two compartments was studied in infertile men, with special attention to varicocele. The reduction state of CoQ(10) in seminal fluid was also investigated. After the first in vitro experiments CoQ(10) was administered to a group of idiopathic asthenozoospermic infertile patients. Seminal analysis showed a significant increase of CoQ(10) both in seminal plasma and in sperm cells, together with an improvement in sperm motility. The increased concentration of CoQ(10) in seminal plasma and sperm cells, the improvement of semen kinetic features after treatment, and the evidence of a direct correlation between CoQ(10) concentrations and sperm motility strongly support a cause/effect relationship. From a general point of view, a deeper knowledge of these molecular mechanisms could lead to a new insight into the so-called unexplained infertility.


Subject(s)
Infertility, Male/physiopathology , Ubiquinone/analogs & derivatives , Antioxidants/physiology , Antioxidants/therapeutic use , Coenzymes , Humans , Infertility, Male/drug therapy , Male , Semen/chemistry , Semen/drug effects , Sperm Count , Sperm Motility/drug effects , Ubiquinone/physiology , Ubiquinone/therapeutic use
9.
Biofactors ; 25(1-4): 241-54, 2005.
Article in English | MEDLINE | ID: mdl-16873953

ABSTRACT

Numerous changes occur post-mortem in fish, affecting its chemical composition and nutritional quality. In the present paper we describe the effect of storage on ice or at -30 degrees C or -80 degrees C on 10 species of Mediterranean fish. Water and lipid soluble antioxidants, lipid pattern and products of oxidative attack on lipids, proteins and DNA were quantified for 7 consecutive days on homogenates of fish light muscle. The earliest events were oxidation of ubiquinol and vitamin C, which disappeared almost completely within 48 hours. Ubiquinol oxidation gave rise to an initial increase of ubiquinone, which peaked at the second day: thereafter ubiquinone itslef decreased, more rapidly and to a greater extent than vitamin E. The decrease in antioxidants was accompanied by significant oxidative damage to lipids, proteins and DNA. TBARS significantly increased beginning from the third day of storage in all species and were linked to a significant reduction in the n-3 PUFA of triglycerides (TG) and phospholipid fractions (PL). A remarkable elevation of protein carbonyls and 8OHdG occurred approximately 24 hours later than PUFA oxidation. For SOD, GPX and GSH significant depletions occurred for all species only at 6th or 7th day, but the final values were always higher than 50% compared to the initial ones. Deep-freezing of the same species at -30 degrees C and -80 degrees C for up to 12 months did not significantly affect the levels of enzymatic antioxidants, the redox couple GSH/GS-SG, n-3 and n-6 PUFA of TG and PL fractions of the light muscle. The only antioxidants, which at -30 degrees C and -80 degrees C appeared to be degraded after 6 and 12 months were ubiquinol and vitamin C. As expected their degradation was higher at -30 degrees C than at -80 degrees C. In fact the average decrease for ubiquinol at -80 degrees C was 42% at 6 and 12 months respectively, whereas at -30 degrees C the decrease was 61% and 87% For vitamin C the average decrease at -80 degrees C was 36% and 67% at 6 and 12 months respectively, and at -30 degrees C it was 61% and 82%. Vitamin E was considerably more stable than ubiquinol and vitamin C. The relative stability of the antioxidants, with the exceptions of ubiquionols, vitamin C and, to a certain extent, vitamin E, was accompanied by a very limited increase in oxidation products. In addition no significant hydrolysis of TG and PL fractions were observed throughout the storage time. The dynamics of lipid, protein and DNA oxidation is discussed in the light of depletion of the various antioxidant systems.


Subject(s)
Antioxidants/metabolism , Fishes/metabolism , Food Preservation/methods , Postmortem Changes , Animals , Ascorbic Acid/metabolism , Frozen Foods/analysis , Lipid Metabolism , Muscles/metabolism , Oxidation-Reduction , Ubiquinone/analogs & derivatives , Ubiquinone/metabolism , Vitamin E/metabolism
10.
Biofactors ; 25(1-4): 219-24, 2005.
Article in English | MEDLINE | ID: mdl-16873950

ABSTRACT

INTRODUCTION: The effect of various dosages and dose strategies of oral coenzyme Q(10) (Q(100) administration on serum Q(10) concentration and bioequivalence of various formulations are not fully known. SUBJECTS AND METHODS: In a randomized, double blind, placebo controlled trial 60 healthy men, aged 18-55 years, were supplemented with various dosages and dose strategies of coenzyme Q(10) soft oil capsules (Myoqinon 100 mg, Pharma Nord, Denmark) or crystalline 100 mg Q(10) powder capsules or placebo. After 20 days blood levels were compared and oxidative load parameters, malondialdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) were monitored to evaluate bioequivalence. All the subjects were advised to take the capsules with meals. Blood samples were collected after 12 hours of overnight fasting at baseline and after 20 days of Q(10) administration. Compliance was evaluated by counting the number of capsules returned by the subjects after the trial. RESULTS: Compliance by capsule counting was >90%. Side effects were negligible. Serum concentrations of Q(10) (average for groups) increased significantly 3-10 fold in the intervention groups compared with the placebo group. Serum response was improved with a divided dose strategy. TBARS and MDA were in the normal ranges at baseline. After 20 days intervention in the 200 mg group TBARS and MDA decreased, but the decrease was only significant for MDA (Fig. 2). CONCLUSIONS: All supplementations increased serum levels of Q(10). Q(10) dissolved in an oil matrix was more effective than the same amount of crystalline Q(10) in raising Q(10) serum levels. 200 mg of oil/soft gel formulation of Q(10) caused a larger increase in Q(10) serum levels than did 100 mg. Divided dosages (2 x 100 mg) of Q(10) caused a larger increase in serum levels of Q(10) than a single dose of 200 mg. Supplementation was associated with decreased oxidative stress as measured by MDA-levels. Indians appear to have low baseline serum coenzyme Q(10) levels which may be due to vegetarian diets. Further studies in larger number of subjects would be necessary to confirm our findings.


Subject(s)
Oxidative Stress/physiology , Ubiquinone/analogs & derivatives , Absorption , Adolescent , Adult , Biological Availability , Coenzymes , Humans , Male , Malondialdehyde/blood , Middle Aged , Solubility , Therapeutic Equivalency , Thiobarbituric Acid Reactive Substances/analysis , Ubiquinone/administration & dosage , Ubiquinone/blood
11.
Biofactors ; 25(1-4): 197-9, 2005.
Article in English | MEDLINE | ID: mdl-16873946

ABSTRACT

In previous works we have demonstrated plasma CoQ10 alterations in pituitary diseases, such as acromegaly or secondary hypothyroidism. However, pituitary lesions can induce complex clinical pictures due to alterations of different endocrine axes controlled by pituitary itself. A further rationale for studying CoQ10 in pituitary-adrenal diseases is related to the common biosynthetic pathway of cholesterol and ubiquinone. We have therefore assayed plasma CoQ10 levels in different conditions with increased or defective activity of pituitary-adrenal axis (3 subjects with ACTH-dependent adrenal hyperplasia, 2 cases of Cushing's disease and 1 case of 17-alpha-hydroxylase deficiency; 10 subjects with secondary hypoadrenalism, including three subjects with also secondary hypothyroidism). CoQ10 levels were significantly lower in isolated hypoadrenalism than in patients with adrenal hyperplasia and multiple pituitary deficiencies (mean +/- SEM: 0.57 +/- 0.04 vs 1.08 +/- 0.08 and 1.10 +/- 0.11 microg/ml, respectively); when corrected for cholesterol levels, the same trend was observed, but did not reach statistical significance. These preliminary data indicate that secretion of adrenal hormones is in some way related to CoQ10 levels, both in augmented and reduced conditions. However, since thyroid hormones have an important role in modulating CoQ10 levels and metabolism, when coexistent, thyroid deficiency seems to play a prevalent role in comparison with adrenal deficiency.


Subject(s)
Adrenal Gland Diseases/physiopathology , Pituitary Diseases/physiopathology , Pituitary-Adrenal System/physiopathology , Ubiquinone/analogs & derivatives , Adrenal Glands/pathology , Adrenal Insufficiency/physiopathology , Adult , Aged , Cholesterol/blood , Coenzymes , Female , Humans , Hydrocortisone/blood , Hyperplasia/physiopathology , Hypothyroidism/physiopathology , Male , Middle Aged , Thyroxine/blood , Triiodothyronine/blood , Ubiquinone/metabolism
12.
Biofactors ; 25(1-4): 201-4, 2005.
Article in English | MEDLINE | ID: mdl-16873947

ABSTRACT

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q 10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. On the other hand, a low-T3 syndrome, due to reduced peripheral conversion from the prohormone T4, is observed in different chronic diseases: this condition is considered an adaptation mechanism, usually not to be corrected by replacement therapy. In order to perform a metabolic evaluation, we have studied a group of 15 patients, aged 69-82 ys, affected by chronic obstructive pulmonary disease (COPD), comparing respiratory indexes, thyroid hormones and CoQ10 levels (also normalized with cholesterol levels) in patients with low (group A) or normal (group B) free-T3 (FT3) concentrations. We found that CoQ10 levels were significantly higher in patients of group A than in B (0.91+/- 0.03 vs 0.7 +/- 0.04 microg/ml respectively); the same difference was observed when comparing the ratios between CoQ10/cholesterol in the two groups (200.16 +/- 8.96 vs 161.08 +/- 7.03 nmol/mmol respectively). These preliminary data seem to indicate that low T3 levels are accompanied by metabolic indexes of a true hypothyroidism in COPD patients. Whether this datum supports the need to perform a replacement therapy in such a condition requires further studies.


Subject(s)
Pulmonary Disease, Chronic Obstructive/blood , Thyroid Hormones/blood , Ubiquinone/analogs & derivatives , Aged , Aged, 80 and over , Coenzymes , Humans , Oxygen/blood , Partial Pressure , Triiodothyronine/blood , Ubiquinone/blood
13.
J Tissue Eng Regen Med ; 9(6): 691-701, 2015 Jun.
Article in English | MEDLINE | ID: mdl-23109511

ABSTRACT

The osteoblast is the bone-forming cell and is derived from mesenchymal stem cells (MSCs). Osteo-inductive substances could represent a useful therapeutic approach during the fracture repair process. The aim of this work was to evaluate the effects of vitamin MK-7, alone or in association with vitamin D3, in differentiating human MSCs (hMSCs) in vitro along the osteoblastic lineage. In particular, primary endpoints of the study include gene and protein markers of osteoblast differentiation. Considering genes involved in bone formation and mineralization, our data show that vitamin MK-7 enhances vitamin D3 gene induction of osteocalcin (OC). Among genes related to cell growth and differentiation, a specific effect of vitamin MK-7 was observed for growth differentiation factor-10 (GDF10) and insulin-like growth factor 1 (IGF1), the latter being also involved in the induction of vascular endothelial growth factors (VEGFA). Accordingly, vitamin co-supplementation greatly affected VEGFA and its receptor fms-related tyrosine kinase 1 (FLT1), a key factor in both angiogenic and osteogenic processes. These results stress the relevance of MK-7 and D3 co-supplementation in the bone-healing process as able to modulate the expression of genes involved in both mineralization and angiogenesis. Moreover, at the protein level co-association of vitamins might provide an optimal balance between induction and carboxylation of osteocalcin, essential for its functionality in the extracellular matrix (ECM). Our results may provide hints for therapeutic application of hMSCs in bone disease, clarifying mechanisms involved in stem cell-mediated bone development, and they also highlight the relevance of co-supplementation strategies, since single supplementations might result in a suboptimal effect.


Subject(s)
Calcification, Physiologic/drug effects , Cholecalciferol/pharmacology , Mesenchymal Stem Cells/metabolism , Neovascularization, Physiologic/drug effects , Osteogenesis/drug effects , Vitamin K 2/analogs & derivatives , Adult , Biomarkers/metabolism , Cell Survival/drug effects , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gene Expression Regulation/drug effects , Humans , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Middle Aged , Osteocalcin/metabolism , Osteogenesis/genetics , Vitamin K 2/pharmacology
14.
Mol Aspects Med ; 18 Suppl: S105-12, 1997.
Article in English | MEDLINE | ID: mdl-9266511

ABSTRACT

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.


Subject(s)
Antioxidants/metabolism , Lipid Peroxidation , Lipoproteins, LDL/metabolism , Ubiquinone/analogs & derivatives , Administration, Oral , Adult , Antioxidants/pharmacokinetics , Coenzymes , Female , Humans , Kinetics , Lipoproteins, LDL/classification , Male , Middle Aged , Oxidation-Reduction , Ubiquinone/administration & dosage , Ubiquinone/blood , Ubiquinone/metabolism , Ubiquinone/pharmacokinetics
15.
Mol Aspects Med ; 18 Suppl: S241-5, 1997.
Article in English | MEDLINE | ID: mdl-9266529

ABSTRACT

It has been widely indicated that several pathological conditions depend upon concomitant risk factors rather than a unique one and that also the putative protective factors do not act alone. For these reasons it could be useful to consider subjects that present sufficiently homogeneous lifestyles (i.e. nutrition and physical activity). We carried out an investigation in a free-living community in order to clarify the possible correlations and differences among plasma metabolic and antioxidant markers in non-agonistic athletes. When subjects were divided in two main groups according to age (35-44 and 45-54 years) without considering the activity they performed, Duncan's analysis of variance revealed that they showed similar characteristics and only triglyceride levels were different. A clear negative correlation was found between vitamin E and VO2max in both age groups, a negative correlation was also found between CoQ10 and VO2max in the younger subjects and finally CoQ10 and vitamin E were also positively correlated in this first group. It appears, therefore, that people with a higher aerobic capacity have lower circulating levels of antioxidants.


Subject(s)
Antioxidants/analysis , Sports , Ubiquinone/analogs & derivatives , Adult , Age Factors , Bicycling , Cardiovascular Diseases/epidemiology , Cholesterol, HDL/blood , Coenzymes , Exercise Test , Humans , Italy , Male , Middle Aged , Oxygen Consumption , Risk Factors , Running , Triglycerides/blood , Ubiquinone/blood , Vitamin E/blood
16.
Mol Aspects Med ; 15 Suppl: s177-85, 1994.
Article in English | MEDLINE | ID: mdl-7752829

ABSTRACT

The authors prepared an experimental animal model of ischemia and reperfusion of the limbs to evaluate in vivo the reactive oxygen species involvement and protective role of coenzyme Q10 in reperfusion injury. A group of male rabbits (untreated group) underwent clamping of abdominal aorta for 3 hr and then declamping; at intervals blood sampling was drawn for coenzyme Q10, vitamin E, lactic acid and creatine kinase assays. Another group of male rabbits (treated group) underwent the same ischemia period but before declamping coenzyme Q10 was administered intra aorta. In untreated group, coenzyme Q10 and vitamin E plasma levels decreased while lactic acid and creatine kinase plasma levels increased during reperfusion. These data demonstrate that, after only 3 hr of ischemia, the extremities show a biochemical reperfusion injury, and this involves an increased consumption of antioxidants such as coenzyme Q10 and vitamin E. In the treated group, the increase of creatine kinase plasma levels during reperfusion was not significant, while the decrease in vitamin E was more marked.


Subject(s)
Extremities/blood supply , Ischemia/drug therapy , Reperfusion Injury/prevention & control , Ubiquinone/analogs & derivatives , Animals , Aorta, Abdominal , Coenzymes , Constriction , Creatine Kinase/blood , Isoenzymes , Lactates/blood , Lactic Acid , Male , Rabbits , Reactive Oxygen Species , Ubiquinone/blood , Ubiquinone/therapeutic use , Vitamin E/blood
17.
Mol Aspects Med ; 18 Suppl: S221-8, 1997.
Article in English | MEDLINE | ID: mdl-9266525

ABSTRACT

Defective sperm function in infertile men has been associated with increased lipid peroxidation and impaired function of antioxidant defenses in spermatozoa. Evidence strongly suggests that CoQ10, a lipid-soluble component of the respiratory chain acts, in its reduced form (ubiquinol), as a potent antioxidant in various biological systems, such as lipoproteins and membranes. In this study we assayed CoQ10 content in both the reduced and oxidized form (ubiquinol/ubiquinone), and hydroperoxide levels in seminal plasma and seminal fluid from 32 subjects with a history of infertility. Our results showed a significant correlation between ubiquinol content and sperm count (r = 0.62; P < 0.05) in seminal plasma. An inverse correlation between ubiquinol content and hydroperoxide levels both in seminal plasma and in seminal fluid (r = -0.56; P = 0.01) was found. Using multiple regression analysis we also found a strong correlation among sperm count, motility and ubiquinol-10 content (P < 0.01) in seminal fluid. An inverse correlation between ubiquinol/ubiquinone ratio and percentage of abnormal morphology was also observed in total fluid. These results suggest that ubiquinol-10 inhibits hydroperoxide formation in seminal fluid and in seminal plasma. Since peroxidation in sperm cells is an important factor affecting male infertility, ubiquinol could assume a diagnostic and/or a therapeutic role in these patients.


Subject(s)
Antioxidants/pharmacology , Hydrogen Peroxide/metabolism , Infertility, Male/metabolism , Lipid Peroxidation/drug effects , Semen/drug effects , Ubiquinone/analogs & derivatives , Adult , Coenzymes , Humans , Hydrogen Peroxide/analysis , Infertility, Male/drug therapy , Male , Oxidation-Reduction , Oxidative Stress , Reactive Oxygen Species/metabolism , Semen/metabolism , Spermatozoa/pathology , Ubiquinone/analysis , Ubiquinone/pharmacology
18.
Mol Aspects Med ; 15 Suppl: s109-15, 1994.
Article in English | MEDLINE | ID: mdl-7752822

ABSTRACT

The interaction of hydrogen peroxide with haem proteins leads readily to the formation of myoglobin and/or haemoglobin higher oxidation states (MbIV and/or HbIV), which are capable of promoting the oxidation of cellular costituents and are probably to blame for myocardic tissue damage in ischaemia/reperfusion. This study supports the evidence that the reduced form of Coenzyme Q, like other reducing agents, has an antioxidant activity exerted through the progressive reduction of ferryl forms (MbIV and/or HbIV) back to met and oxy forms (Mb and/or HbIIO2). Furthermore, the strong inactivation afforded by ferryl states of myoglobin on several enzymes, especially creatine kinase (CK), can be prevented by the addition of ubiquinol which protects the enzyme from the oxidative modifications. The ability of ubiquinol to recycle ferryl states of haem proteins provides a novel antioxidant mechanism for Coenzyme Q, besides its direct or indirect antiperoxidative activity, and may represent an important defense mechanism against oxidative tissue injury.


Subject(s)
Antioxidants/pharmacology , Hemoglobins/metabolism , Myoglobin/metabolism , Ubiquinone/pharmacology , Animals , Apoproteins/metabolism , Cattle , Creatine Kinase/metabolism , Free Radicals , Horses , Humans , Metmyoglobin/metabolism , Oxidation-Reduction , Ubiquinone/analogs & derivatives
19.
Mol Aspects Med ; 15 Suppl: s249-55, 1994.
Article in English | MEDLINE | ID: mdl-7752837

ABSTRACT

The levels of Coenzyme Q10 (CoQ10) were determined by HPLC in seminal fluid samples obtained from 77 patients who performed a standard semen analysis for infertility, previous phlogosis or varicocele. CoQ10 was determined in total seminal fluid (n = 60), in seminal plasma (n = 44) and in the cell pellet (n = 37). The molecule, in total fluid, showed a linear correlation with sperm count and motility. In the pellet of spermatozoa, a trend toward an inverse correlation between CoQ10 (expressed as ng/10(6) cells) and semen parameters could be observed. A different pattern was shown in varicocele patients, in whom, in total fluid, the correlation between CoQ10 and sperm count was preserved, but the one between CoQ10 and sperm motility was lacking; moreover, a higher proportion of CoQ10 was present in seminal plasma, and the inverse trend between cellular CoQ10 and sperm count and motility was not observed. These data suggest a pathophysiological role of ubiquinone in human seminal fluid and a molecular defect in the spermatozoa of varicocele patients.


Subject(s)
Semen/chemistry , Ubiquinone/analogs & derivatives , Adult , Coenzymes , Genital Diseases, Male/metabolism , Humans , Infertility, Male/metabolism , Inflammation , Male , Oligospermia/metabolism , Sperm Count , Sperm Motility , Ubiquinone/analysis , Varicocele/metabolism
20.
Mol Aspects Med ; 15 Suppl: s257-63, 1994.
Article in English | MEDLINE | ID: mdl-7752838

ABSTRACT

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty-six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24-hour automatic blood pressure monitoring were determined.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Ubiquinone/analogs & derivatives , Adult , Aged , Aldosterone/urine , Blood Pressure/drug effects , Cholesterol/blood , Cholesterol, HDL/blood , Coenzymes , Echocardiography , Electrocardiography , Endothelins/blood , Female , Humans , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , Hypertension/blood , Hypertension/complications , Male , Middle Aged , Potassium/metabolism , Renin/blood , Sodium/metabolism , Treatment Outcome , Ubiquinone/blood , Ubiquinone/therapeutic use , Vascular Resistance/drug effects
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