Biofactors - Volume 25, issue 1-4

Article Type: Other

Citation: BioFactors, vol. 25, no. 1-4, pp. 1-1, 2005

Article Type: Other

Citation: BioFactors, vol. 25, no. 1-4, pp. 3-3, 2005

Authors: Genova, Maria Luisa | Bianchi, Cristina | Lenaz, Giorgio

Article Type: Research Article

Abstract: In this review we examine early and recent evidence for an aggregated organization of the mitochondrial respiratory chain. Blue Native Electrophoresis suggests that in several types of mitochondria Complexes I, III and IV are aggregated as fixed supramolecular units having stoichiometric proportions of each individual complex. Kinetic evidence by flux control analysis agrees with this view, however the presence of Complex IV in bovine mitochondria cannot be demonstrated, presumably due to high levels of free …Complex. Since most Coenzyme Q appears to be largely free in the lipid bilayer of the inner membrane, binding of Coenzyme Q molecules to the Complex I–III aggregate is forced by its dissociation equilibrium; furthermore free Coenzyme Q is required for succinate-supported respiration and reverse electron transfer. The advantage of the supercomplex organization is in a more efficient electron transfer by channelling of the redox intermediates and in the requirement of a supramolecular structure for the correct assembly of the individual complexes. Preliminary evidence suggests that dilution of the membrane proteins with extra phospholipids and lipid peroxidation may disrupt the supercomplex organization. This finding has pathophysiological implications, in view of the role of oxidative stress in the pathogenesis of many diseases. Show more

Keywords: Coenzyme Q, bound, pool, respiratory chain, supercomplexes, flux control analysis, electron channelling

Citation: BioFactors, vol. 25, no. 1-4, pp. 5-20, 2005

Authors: Gavilán, Ángela | Asencio, Claudio | Cabello, Juan | Rodríguez-Aguilera, Juan C. | Schnabel, Ralf | Navas, Plácido

Article Type: Research Article

Abstract: Ubiquinone is an essential molecule in aerobic organisms to achieve both, ATP synthesis and antioxidant defence. Mutants in genes responsible of ubiquinone biosynthesis lead to non-respiring petite yeast. In C. elegans, coq-7/clk-1 but not coq-3 mutants live longer than wild type showing a 'slowed' phenotype. In this paper we demonstrate that absence in ubiquinone in coq-1, coq-2 or coq-8 mutants lead to larval development arrest, slowed pharyngeal pumping, eventual paralysis and cell death. All …these features emerge during larval development, whereas embryo development appeared similar to that of wild type individuals. Dietary coenzyme Q did not restore any of the alterations found in these coq mutants. These phenomena suggest that coenzyme Q mutants unable to synthesize this molecule develop a deleterious phenotype leading to lethality. On the contrary, phenotype of C. elegans coq-7/clk-1 mutants may be a unique phenotype than can not generalize to mutants in ubiquinone biosynthesis. This particular phenotype may not be based on the absence of endogenous coenzyme Q, but to the simultaneous presence of dietary coenzyme Q and the its biosynthesis intermediate demethoxy-coenzyme Q. Show more

Keywords: Coenzyme Q, aging, C. elegans, development

Citation: BioFactors, vol. 25, no. 1-4, pp. 21-29, 2005

Authors: González-Aragón, David | Burón, María I. | López-Lluch, Guillermo | Hermán, María D. | Gómez-Díaz, Consuelo | Navas, Plácido | Villalba, José M.

Article Type: Research Article

Abstract: The present work was set to study how CoQ concentrations affected steady-state levels of superoxide in a cellular model of partial CoQ_{10} deficiency in cultured human myeloid leukemia HL-60 cells. Culturing HL-60 cells in the presence of p-aminobenzoate, a competitive inhibitor of polyprenyl-4-hydroxybenzoate transferase (Coq2p), produced a significant decrease of CoQ_{10} levels without affecting cell viability. Concomitant decreases in CoQ-dependent electron transport activity and mitochondrial membrane potential were …observed under these conditions. Intracellular superoxide was significantly elevated in cells treated with p-aminobenzoate, both under serum-containing and serum-free conditions, and this effect was reversed by exogenous CoQ_{10} . A slight increase of superoxide was also observed in CoQ_{10} -supplemented cells in the absence of serum. Our results support a requirement for CoQ_{10} to control superoxide levels in HL-60 cells. The importance of extramitochondrial sources of superoxide in cells with impaired CoQ_{10} biosynthesis is discussed. Show more

Citation: BioFactors, vol. 25, no. 1-4, pp. 31-41, 2005

Authors: De Luca, Thomas | Morré, Dorothy M. | Zhao, Haiyun | Morré, D. James

Article Type: Research Article

Abstract: To elucidate possible biochemical links between growth arrest from antiproliferative chemotherapeutic agents and apoptosis, our work has focused on agents (EGCg, capsaicin, cis platinum, adriamycin, anti-tumor sulfonylureas, phenoxodiol) that target tNOX. tNOX is a cancer-specific cell surface NADH oxidase (ECTO-NOX protein), that functions in cancer cells as the terminal oxidase for plasma membrane electron transport. When tNOX is active, coenzyme Q_{10} (ubiquinone) of the plasma membrane is oxidized and NADH …is oxidized at the cytosolic surface of the plasma membrane. However, when tNOX is inhibited and plasma membrane electron transport is diminished, both reduced coenzyme Q_{10} (ubiquinol) and NADH would be expected to accumulate. To relate inhibition of plasma membrane redox to increased ceramide levels and arrest of cell proliferation in G_{1} and apoptosis, we show that neutral sphingomyelinase, a major contributor to plasma membrane ceramide, is inhibited by reduced glutathione and ubiquinone. Ubiquinol is without effect or stimulates. In contrast, sphingosine kinase, which generates anti-apoptotic sphingosine-1-phosphate, is stimulated by ubiquinone but inhibited by ubiquinol and NADH. Thus, the quinone and pyridine nucleotide products of plasma membrane redox, ubiquinone and ubiquinol, as well as NAD^{+} and NADH, may directly modulate in a reciprocal manner two key plasma membrane enzymes, sphingomyelinase and sphingosine kinase, potentially leading to G_{1} arrest (increase in ceramide) and apoptosis (loss of sphingosine-1-phosphate). As such, the findings provide potential links between coenzyme Q_{10} -mediated plasma membrane electron transport and the anticancer action of several clinically-relevant anticancer agents. Show more

Keywords: Apoptosis, ECTO-NOX, NADH oxidase, tNOX, cancer, capsaicin, ceramide, coenzyme Q, (-)-epigallocatechin-3-gallate (EGCg), plasma membrane electron transport, sphingomyelinase, sphingosine-1-phosphate, sphingosine kinase

Citation: BioFactors, vol. 25, no. 1-4, pp. 43-60, 2005

Authors: Palan, Prabhudas R. | Connell, Kathleen | Ramirez, Elizabeth | Inegbenijie, Christian | Gavara, Rachana Y. | Ouseph, Jacob A. | Mikhail, Magdy S.

Article Type: Research Article

Abstract: The present study examines the influence of menopause and hormone replacement therapy (HRT) on serum levels of coenzyme Q_{10} and other lipid-soluble antioxidants in normal women. Serum levels of coenzyme Q_{10} , α-tocopherol, γ-tocopherol, β-carotene and lycopene in 50 premenopausal women (not using oral contraceptives), 33 healthy postmenopausal and 15 postmenopausal women on HRT ("Prempo"; combination of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone acetate) were …measured by high-pressure liquid chromatography. Lipid profiles were also analyzed. Significantly higher serum coenzyme Q_{10} and α-tocopherol levels were detected in postmenopausal compared with premenopausal women (P<0.05, and < 0.001); whereas, in postmenopausal subjects on HRT, we detected a significant decrease in coenzyme Q_{10} and γ-tocopherol levels (P<0.001, and < 0.05) and increased α-tocopherol levels (P<0.05). Serum levels of β-carotene, lycopene, LDL, HDL, cholesterol and triglyceride were comparable among the study groups. Coenzyme Q_{10} is postulated to be involved in preventing cardiovascular disease (CVD) because of its bioenergetics role in the mitochondrial respiratory chain and its antioxidant properties at the mitochondrial and extramitochondrial levels. The decrease in serum concentrations of coenzyme Q_{10} , produced by HRT, may promote oxygen free radical-induced membrane damage and may, thus alter cardiovascular risk in postmenopausal women. HRT-induced reductions in lipid-soluble antioxidant(s) levels, and its potential consequences on CVD, needs to be further investigated. Show more

Keywords: Menopause, hormone replacement therapy, coenzyme Q_{10}, tocopherols, antioxidants

Citation: BioFactors, vol. 25, no. 1-4, pp. 61-66, 2005

Authors: Niklowitz, Petra | Menke, Thomas | Giffei, Jörg | Andler, Werner

Article Type: Research Article

Abstract: In contrast to other lipophilic antioxidants Coenzyme Q10 originates from food intake as well as from endogenous synthesis. The CoQ10 concentration and lipid content of maternal milk and maternal plasma was investigated during early lactation. Breast milk was obtained from 23 women: A: colostrums (24–48 hours postpartum), B: transitional milk (day 7 pp), C: mature milk (day 14 pp). At the same time capillary blood specimens were collected. Milk and plasma were stored at …−84°C until CoQ10 was analysed after hexane extraction by HPLC. The lipid content was determined by PAP-analysis of cholesterol. The plasma content of CoQ10 was the highest soon after delivery (A: 1.29, B:1.20, C:1.07 pmol/μl; Wilcoxon p<0.05 A vs. C and B vs. C). This tendency was still evident after lipid-adjustment (A:209, B:180, C:175 μmol CoQ10/mol cholesterol; Wilcoxon p<0.01 A vs. B and C). The level of CoQ10 in milk showed a gradual decline during early lactation (A:0.80, B:0.57, C:0.44 pmol/μl; Wilcoxon p<0.02 A vs. B and C). After lipid-adjustment this tendency became even more evident (A: 137, B:86, C:67 μmol CoQ10/mol cholesterol; Wilcoxon p<0.002 A vs. B and C, p<0.05 B vs. C). The content of CoQ10 in plasma and milk showed a correlation with early milk (Spearman p<0.005) but not with mature milk. Although lipid content is low the colostrums is a rich source for the lipophilic antioxidant CoQ10. Show more

Keywords: Coenzyme Q10, colostrum, milk, human, lactation

Citation: BioFactors, vol. 25, no. 1-4, pp. 67-72, 2005

Authors: Quiles, José L. | Ochoa, Julio J. | Battino, Maurizio | Gutierrez-Rios, Purificación | Nepomuceno, Eduardo A. | Frías, Magdalena López | Huertas, Jesús R. | Mataix, José

Article Type: Research Article

Abstract: Life-long low-dosage supplementation of coenzyme Q_{10} (CoQ_{10}) is studied in relation to the antioxidant status and DNA damage. Thirty-two male rats were assigned into two experimental groups differing in the supplementation or not with 0.7 mg/kg/day of CoQ_{10} . Eight rats per group were killed at 6 and 24 months. Plasma retinol, α-tocopherol, coenzyme Q, total antioxidant capacity and fatty acids were analysed. DNA strand breaks were …studied in peripheral blood lymphocytes. Aging and supplementation led to significantly higher values for CoQ homologues, retinol and α-tocopherol. No difference in total antioxidant capacity was detected at 6 months but significantly lower values were found in aged control animals. Similar DNA strand breaks levels were found at 6 months. Aging led to significantly higher DNA strand breaks levels in both groups but animals supplemented with CoQ_{10} led to a significantly lower increase in that marker. Aged rats showed significantly higher polyunsaturated fatty acids. This study demonstrates that lifelong intake of a low dosage of CoQ_{10} enhances plasma levels of CoQ_{9} , CoQ_{10} , α-tocopherol and retinol. In addition, CoQ_{10} supplementation attenuates the age-related fall in total antioxidant capacity of plasma and the increase in DNA damage in peripheral blood lymphocytes. Show more

Keywords: Comet assay, DNA strand breaks, ubiquinone, coenzyme Q_{9}, α-tocopherol, retinol, fatty acids, total antioxidant capacity

Citation: BioFactors, vol. 25, no. 1-4, pp. 73-86, 2005

Authors: Nohl, Hans | Rohr-Udilova, Natalia | Gille, Lars | Bieberschulte, Werner | Jurek, Daniela | Marian, Brigitte | Schulte-Hermann, Rolf

Article Type: Research Article

Abstract: High consumption of dietary fat promotes colon carcinogenesis. While this effect is well known the underlying mechanism is not understood. Fatty acid hydroperoxides (LOOH) arise from unsaturated fatty acids in the presence of oxygen and elevated temperature during food processing. An approach was made starting from the assumption that LOOH are present in dietary fats as a result of boiling. LOOH undergoes homolytic cleavage in the presence of iron. We studied their effects on gene expression …in colorectal tumour cells using linoleic acid hydroperoxide (LOOH) as model compound. Addition to the medium of LT97 adenoma and SW480 carcinoma cells enhanced the production of hydrogen peroxide. Both cell lines were observed to increase VEGF and COX-II expression based on mRNA. Expression of VEGF was inhibited by caroverine and ubiquinon. Show more

Citation: BioFactors, vol. 25, no. 1-4, pp. 87-95, 2005

Authors: Li, Geng | Zou, Liang-Yu | Cao, Chun-Mei | Yang, Edward S.

Article Type: Research Article

Abstract: Coenzyme Q10 (CoQ10) is an essential biological cofactor which increases brain mitochondrial concentration and exerts neuroprotective effects. In the present study, we exposed SHSY5Y neuroblastoma cells to neurotoxic beta amyloid peptides (Aβ) and oxygen glucose deprivation (OGD) to investigate the neuroprotective effect of 10μM CoQ10 by measuring (i) cell viability by the MTT assay, (ii) opening of the mitochondrial permeability transition pore via the fluorescence intensity of calcein-AM, and (iii) superoxide anion …concentration by hydroethidine. Cell viability (mean ± S.E.M.) was 55.5 ± 0.8% in the group exposed to Aβ + OGD, a value lower than that in the Aβ or OGD group alone (P<0.01). CoQ10 had no neuroprotective effect on cell death induced by either Aβ or OGD, but increased cell survival in the Aβ + OGD group to 57.3 ± 1.7%, which was higher than in the group treated with vehicle (P<0.05). The neuroprotective effect of CoQ10 was blocked by administration of 20μM atractyloside. Pore opening and superoxide anion concentration were increased in the Aβ + OGD group relative to sham control (P<0.01), and were attenuated to the sham level (P>0.05) when CoQ10 was administered. Our results demonstrate that CoQ10 protects neuronal cells against Aβ neurotoxicity together with OGD by inhibiting the opening of the pore and reducing the concentration of superoxide anion. Show more

Keywords: Coenzyme Q10, Beta amyloid, oxygen-glucose deprivation, mitochondrial permeability transition pore, superoxide anion

Citation: BioFactors, vol. 25, no. 1-4, pp. 97-107, 2005

Authors: Montero, R. | Artuch, R. | Briones, P. | Nascimento, A. | García-Cazorla, A. | Vilaseca, M.A. | Sánchez-Alcázar, J.A. | Navas, P. | Montoya, J. | Pineda, M.

Article Type: Research Article

Abstract: Coenzyme Q_{10} (CoQ) deficiency syndrome is a disorder of unknown ethiology that may cause different forms of mitochondrial encephalomyopathy. In the present study our aim was to analyse CoQ concentration and mitochondrial respiratory chain (MRC) enzyme activities in muscle biopsies of patients with clinical suspicion and/or biochemical-molecular diagnosis of a mitochondrial disorder. We studied 36 patients classified into 3 groups: 1) 14 patients without a definitive diagnosis of mitochondrial disease, …2) 13 patients with decreased CI+III and II+III activities of the MRC, and 3) 9 patients with definitive diagnosis of mitochondrial disease. Only 1 of the 14 patients of group 1 showed slightly reduced CoQ values in muscle. Six of the 13 patients from group 2 showed partial CoQ deficiency in muscle and 1 of the 9 cases from group 3 presented a slight CoQ deficiency. Significantly positive correlation was observed between CI+III and CII+III activities with CoQ concentrations in the 36 muscle homogenates from patients (r=0.555; p=0.001; and r=0.460; p=0.005, respectively). In conclusion, measurement of MRC enzyme activities is a useful tool for the detection of CoQ deficiency, which should be confirmed by CoQ quantification. Show more

Keywords: Coenzyme Q_{10} deficiency, mitochondrial encephalomyopathies, paediatric patients

Citation: BioFactors, vol. 25, no. 1-4, pp. 109-115, 2005

Authors: Shults, Clifford W. | Haas, Richard

Article Type: Research Article

Citation: BioFactors, vol. 25, no. 1-4, pp. 117-126, 2005

Authors: Mancinelli, Rino | Vargiu, Romina | Cappai, Antonello | Floris, Giuseppe | Fraschini, Matteo | Faa, Gavino

Article Type: Research Article

Abstract: Mechanisms underlying dilated cardiomyopathy (DCM) are poorly understood and effective therapy is still unavailable. The aim of this study was to examine the heart ultrastructure and dynamic of BIO T0-2 cardiomyopathic hamsters, an animal model of DCM, and to study in these animals, the effects of a co-formulation (HS12607) of propionyl-L-carnitine, coenzyme Q_{10} and omega-3 fatty acids on cardiac mechanical parameters. Sarcomere length, Frank-Starling mechanism and force-frequency relations were studied …on isolated ventricular papillary muscle from age-matched BIO F1B normal Syrian hamsters, BIO T0-2 control and BIO T0-2 HS12607-treated cardiomyopathic Syrian hamsters. At the optimum length to maximum active force, electron microscopy of left ventricular papillary muscle revealed that seven out of ten muscles studied showed shorter sarcomeres (1.20 ± 0.29μm), and the remaining three showed longer sarcomeres (2.80 ± 0.13μm), compared to those of normal hamsters (2.05± 0.06μm, n=10). Severe alterations of the Frank-Starling mechanism, force-frequency relations and derivative parameters of contractile waves were also observed in vitro in the BIO T0-2 control hamsters. Long-term (8 weeks) treatment with HS12607 prevented alterations in sarcomere length in the BIO T0-2 cardiomyopathic hamsters; the Frank-Starling mechanism and force-frequency relations were also significantly (P<0.05) improved in these hamsters. Therefore results of the present study strongly suggest the need for clinical studies on metabolic therapeutic intervention in the effort to stop the progression of dilated cardiomyopathy. Show more

Keywords: BIO T0-2 Syrian hamster, dilated cardiomyopathy, propionyl-L-carnitine, coenzyme Q_{10}, omega-3 fatty acids

Citation: BioFactors, vol. 25, no. 1-4, pp. 127-135, 2005

Authors: Belardinelli, Romualdo | Muçaj, Andi | Lacalaprice, Francesca | Solenghi, Maridia | Principi, Federica | Tiano, Luca | Littarru, Gian Paolo

Article Type: Research Article

Abstract: Background: There is evidence that plasma CoQ_{10} levels decrease in patients with advanced chronic heart failure (CHF). Objective: To investigate whether oral CoQ_{10} supplementation could improve cardiocirculatory efficiency in patients with CHF. Methods: We studied 21 patients in NYHA class II and III (18M, 3W, mean age 59 ±9 years) with stable CHF secondary to ischemic heart disease (ejection fraction 37 ± 7%), using a double-blind, …placebo-controlled cross-over design. Patients were assigned to oral CoQ_{10} (100 mg tid) and to placebo for 4 weeks, respectively. Results: CoQ_{10} supplementation resulted in a threefold increase in plasma CoQ_{10} level (P<0.0001 vs placebo). Systolic wall thickening score index (SWTI) was improved both at rest and peak dobutamine stress echo after CoQ_{10} supplementation (+12.1 and 15.6%, respectively, P<0.05 vs placebo). Left ventricular ejection fraction improved significantly also at peak dobutamine (15% from study entry P<0.0001) in relation to a decrease in LV end-systolic volume index (from 57 ± 7 mL/m^2 to 45 mL/m^2 , P<0.001). Improvement in the contractile response was more evident among initially akinetic (+33%) and hypokinetic (+25%) segments than dyskinetic ones (+6%). Improvement in SWTI was correlated with changes in plasma CoQ_{10} levels (r=−0.52, P<0.005). Peak VO_2 was also improved after CoQ_{10} as compared with placebo (+13%, <0.005). No side effects were reported with CoQ_{10} . Conclusions: Oral CoQ_{10} improves LV contractility in CHF without any side effects. This improvement is associated with an enhanced functional capacity. Show more

Keywords: Coenzyme Q_{10}, chronic heart failure, left ventricular contractility, functional capacity

Citation: BioFactors, vol. 25, no. 1-4, pp. 137-145, 2005

Authors: Langsjoen, Peter H. | Langsjoen, Jens O. | Langsjoen, Alena M. | Lucas, Lindsay A.

Article Type: Research Article

Abstract: Fifty consecutive new cardiology clinic patients who were on statin drug therapy (for an average of 28 months) on their initial visit were evaluated for possible adverse statin effects (myalgia, fatigue, dyspnea, memory loss, and peripheral neuropathy). All patients discontinued statin therapy due to side effects and began supplemental CoQ_{10} at an average of 240 mg/day upon initial visit. Patients have been followed for an average of 22 months with 84% of the patients …followed now for more than 12 months. The prevalence of patient symptoms on initial visit and on most recent follow-up demonstrated a decrease in fatigue from 84% to 16%, myalgia from 64% to 6%, dyspnea from 58% to 12%, memory loss from 8% to 4% and peripheral neuropathy from 10% to 2%. There were two deaths from lung cancer and one death from aortic stenosis with no strokes or myocardial infarctions. Measurements of heart function either improved or remained stable in the majority of patients. We conclude that statin-related side effects, including statin cardiomyopathy, are far more common than previously published and are reversible with the combination of statin discontinuation and supplemental CoQ_{10} . We saw no adverse consequences from statin discontinuation. Show more

Keywords: Statin cardiomyopathy, coenzyme Q_{10}, CoQ_{10}, ubiquinone, statins, statin side effects, HMG-CoA reductase inhibitors

Citation: BioFactors, vol. 25, no. 1-4, pp. 147-152, 2005

Authors: Teran, Enrique | Vivero, Sandra | Racines-Orbe, Marcia | Castellanos, Alberto | Chuncha, Galo | Enriquez, Galo | Moya, Walter

Article Type: Research Article

Abstract: Preeclampsia is a common (∼7% of all pregnancies) disorder of pregnancy in which the normal hemodynamic response to pregnancy is compromised. Despite many years of intensive research, the pathogenesis of preeclampsia is still not fully understood. The objective of the present study was to investigate the levels of coenzyme Q_{10} (CoQ_{10}) in placental tissue compared to maternal and umbilical cord levels both during normal pregnancy and in those complicated …with preeclampsia. Pregnant women (n=30) and women with preeclampsia (n=30) were included. Maternal, newborn cord blood levels and placental content of coenzyme Q_{10} were measured by high performance liquid chromatography (HPLC). Plasma coenzyme Q_{10} levels were significantly higher in normal pregnant women than in women with preeclampsia. CoQ_{10} content in placenta from women with preeclampsia (mean 0.28 SEM 0.11 nmol/mg protein) was significantly higher compared to normal pregnancy (mean 0.09 SEM 0.01 nmol/mg protein; p=0.05). Levels of CoQ_{10} in cord blood from normal pregnant women (mean 0.30 SEM 0.05μmol/l) were significantly lower than in preeclamptic women (mean 4.03 SEM 2.38μmol/l). In conclusion, these data indicate a possible involvement of CoQ_{10} in preeclampsia that might bear deep physiopathological significance and deserve to be further elucidated. Show more

Keywords: Coenzyme Q_{10}, pregnancy, preeclampsia, placenta, cord blood

Citation: BioFactors, vol. 25, no. 1-4, pp. 153-158, 2005

Authors: Giannubilo, Stefano R. | Tranquilli, Andrea L. | Santolini, Cristina | Prinicipi, Federica | Mancinelli, Romina | Littarru, Gian Paolo

Article Type: Research Article

Abstract: Oxidative stress is considered a key factor in HELLP syndrome, a severe complication of preeclampsia in pregnancy. In the present study we analysed the content of Coenzyme Q_{10} (CoQ_{10} ), a fundamental component of the mitochondrial respiratory chain and recognized lipophilic antioxidant, in placentas from women affected by HELLP syndrome and compared them with the relative controls. Twenty-eight patients with HELLP syndrome and twenty-eight age-matched healthy pregnant …controls were enrolled. Two aliquots of placental tissue were taken immediately after delivery and placed into liquid nitrogen. Thawed samples were homogenised by Ultra-Turrax; total protein and CoQ_{10} concentration were thereafter analysed. CoQ_{10} concentration was 0.162 ± 0.07μg/mg protein in HELLP syndrome versus 0.87 ± 0.003μg/mg protein in controls, the difference being highly significant. A positive correlation, within the placentas from HELLP, was found between the weight of the new-born and CoQ_{10} /protein ratio. A significant positive correlation was also present between CoQ_{10} /protein ratio and Apgar at 1st and 5th minute as well as between CoQ_{10} /protein ratio and the median cerebral artery pulsatility index. The increase in placental CoQ_{10} in this syndrome might derive from a compensatory mechanism in a situation of increased oxidative stress. Show more

Keywords: CoQ_{10}, pregnancy, placenta, HELLP syndrome, oxidative stress

Citation: BioFactors, vol. 25, no. 1-4, pp. 159-163, 2005

Authors: Mancini, A. | De Marinis, L. | Littarru, G.P. | Balercia, G.

Article Type: Research Article

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 _{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. Show more

Keywords: Coenzyme Q_{10}, oxidative stress, infertility

Citation: BioFactors, vol. 25, no. 1-4, pp. 165-174, 2005

Authors: Ashida, Yutaka | Yamanishi, Haruyo | Terada, Takatomo | Oota, Norihito | Sekine, Kyoichi | Watabe, Kazuo

Article Type: Research Article

Abstract: We have already shown that prolonged supplementation of CoQ_{10} in humans reduces the wrinkle area rate and wrinkle volume per unit area in the corner of the eye. CoQ_{10} supplementation is known to increase the CoQ_{10} level in serum and in many organs; however, the level of CoQ_{10} in skin has not yet been fully investigated yet. We examined whether CoQ_{10} intake elevates the CoQ_{10} …and CoQ_{9} levels in epidermis, dermis, serum and other organs (kidney, heart, brain, muscle and crystalline lens) in 43-week-old hairless male mice. We also established a method using a high performance liquid chromatograph equipped with an electrochemical detector (HPLC-ECD) to simultaneously quantify CoQ_{9} and CoQ_{10} in the tissues. CoQ_{10} (0, 1, 100 mg/kg p.o.) was administered daily for 2 weeks. CoQ_{10} supplementation of 100 mg/kg increased the serum and epidermal CoQ_{10} levels significantly, but did not increase the CoQ_{10} levels in either dermis or other organs. In conclusion, we showed that CoQ_{10} intake elevates the epidermal CoQ_{10} level, which may be a prerequisite to the reduction of wrinkles and other benefits related to the potent antioxidant and energizing effects of CoQ_{10} in skin. Show more

Keywords: Coenzyme Q_{10}, coenzyme Q_{9}, HPLC, ECD, diet, skin, epidermis, serum

Citation: BioFactors, vol. 25, no. 1-4, pp. 175-178, 2005

Authors: Blatt, T. | Lenz, H. | Koop, U. | Jaspers, S. | Weber, T. | Mummert, C. | Wittern, K.-P. | Stäb, F. | Wenck, H.

Article Type: Research Article

Abstract: As an organism ages, there is a decline in mitochondrial function and cellular energy balance. This decline is both accelerated by and can cause the formation of reactive oxygen species (ROS) that damage nuclear and mitochondrial DNA, lipid membranes as well as structural and catalytic proteins, especially those involved in energetic pathways of cells. Further, ROS have also been linked to some of the detrimental skin changes that occur as a result of photoaging. …We have previously shown that levels of Coenzyme Q10 (CoQ10), a component of the respiratory chain in mitochondria, are reduced in skin cells from aging donors, and that topical supplementation can ameliorate processes involved in skin aging. Creatine is another important component of the cellular energy system and phosphocreatine, its phosphorylated form, functions as a reservoir for high energy phosphates. Unfortunately the creatine system and thus the energy storage mechanism in skin are negatively affected by aging and conditions of oxidative stress. This article reviews some of our in vivo data about the synergistic effects of combining a stabilized form of Creatine with CoQ10 and clearly depicts their beneficial effects as active ingredients in topical formulations. Show more

Keywords: CoQ10, creatine, topical application, skin aging, wrinkles, energy

Citation: BioFactors, vol. 25, no. 1-4, pp. 179-185, 2005

Authors: Tiano, Luca | Littarru, Gian Paolo | Principi, Federica | Orlandi, Marco | Santoro, Lucia | Carnevali, Paola | Gabrielli, Orazio

Article Type: Research Article

Abstract: Single cell gel electrophoresis (SCGE), also known as comet assay is a widely used method to detect DNA damage. Its use is nonetheless subjected to some pitfalls, due to differences in experimental set-up, to operator-dependent variability and to quantification of the comets, which is usually accomplished by visual scoring or by image-analysis software. Biological variability in the extent of DNA damage must be taken into account particularly regarding in vivo studies. In the present paper we …propose an improved methodology where major features are: a) cryopreservation of lymphocytes collected at different time points and simultaneous analysis in a single run; b) use of an internal control on each slide; c) development of a custom-made software with semi – automated image analysis in order to overcome operator dependent variability. Cryopreservation was accomplished by storing lymphocytes in liquid nitrogen in a solution commonly used for preserving vital cells to be reinfused. We found that this procedure did not alter DNA after 2 and 4 months of storage. The use of quality control from a batch of aliquoted lymphocytes from a healthy donor on each slide, enabled to highlight possible experimental anomalies as well as verify inter-experimental variability. Moreover, by using a newly developed software able to automatically recognise comets we minimised operator-dependent variability in the scoring process. This improved methodology is proposed for longitudinal in vivo studies and in the present work its application made it possible to assess a significant increase of DNA in pediatric Down Syndrome patients compared to healthy controls of the same age. Show more

Keywords: Comet assay, Down Syndrome, DNA damage

Citation: BioFactors, vol. 25, no. 1-4, pp. 187-195, 2005

Authors: Mancini, A. | Bianchi, A. | Fusco, A. | Sacco, E. | Leone, E. | Tilaro, L. | Porcelli, T. | Giampietro, A. | Principi, F. | De Marinis, L. | Littarru, G.P.

Article Type: Research Article

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-α-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 μg/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. Show more

Keywords: Coenzyme Q_{10}, pituitary, adrenal gland, thyroid

Citation: BioFactors, vol. 25, no. 1-4, pp. 197-199, 2005

Authors: Mancini, A. | Corbo, G.M. | Gaballo, A. | Valente, S. | Gigliotti, P. | Cimino, V. | De Marinis, L. | Principi, F. | Littarru, G.P.

Article Type: Research Article

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 μg/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. Show more

Keywords: Coenzyme Q10, thyroid hormones, "low-T3" syndrome, chronic obstructive pulmonary disease

Citation: BioFactors, vol. 25, no. 1-4, pp. 201-204, 2005

Authors: Sekine, K. | Ota, N. | Nishii, M. | Uetake, T. | Shimadzu, M.

Article Type: Research Article

Abstract: Coenzyme Q10 (CoQ_{10}) levels in human saliva were measured by HPLC with a highly sensitive electrochemical detector (ECD) and a special concentration column. This HPLC system showed satisfactory analytical results within the standard range of 0.78–50 ng/ml. We also found a significant correlation between CoQ_{10} levels in plasma and in saliva from parotid glands, while this correlation was lacking between plasma CoQ10 and CoQ10 in whole saliva. Unlike in plasma, there are …some fluctuations of saliva CoQ_{10} levels throughout the day. A good correlation was obtained by colleting parotid gland saliva at times between meals. The mean saliva CoQ_{10} level for 55 healthy volunteers was 17.0 ng/ml (S.D. 6.8 ng/ml); approximately one fiftieth of that in plasma. Regarding the influence of oral supplementation, CoQ_{10} was analyzed in plasma and parotid gland saliva from 20 healthy volunteers supplemented daily with 100 mg of CoQ_{10} for the first week and 200 mg for the second. The plasma CoQ_{10} levels of all volunteers increased to different extents in accordance with the CoQ_{10} daily intake and the corresponding change in saliva showed almost the same trend. Show more

Keywords: Coenzyme Q_{10}, CoQ_{10}, ubidecarenol, ubidecarenone, plasma, saliva, parotid gland, oxidative stress, supplementation, measurement, performance test, HPLC

Citation: BioFactors, vol. 25, no. 1-4, pp. 205-211, 2005

Authors: Battino, Maurizio | Bompadre, Stefano | Politi, Alessia | Fioroni, Massimiliano | Rubini, Corrado | Bullon, Pedro

Article Type: Research Article

Abstract: Reactive oxygen species and antioxidant status in periodontal diseases and periodontal-related pathologies is an item of growing interest. Immunohistochemical approach may be usefully employed in the study of soft tissues affected by periodontal disease, giving valuable information on tissue morphology and vascular proliferation that depends directly on the inflammatory state. In order to study CoQ_{10} and vitamin E content in healthy gingiva and in gingivitis a new adaptation to previously published …methods for their determination was adopted. During gingivitis tissue displayed a large inflammatory infiltration in the lamina propria and a VEGF positive squamous epithelium. The inflammatory infiltration consisted mainly of lymphocytes, plasma cells and neutrophils. Vitamin E dramatically decreased and CoQ_{10} remained unchanged despite the increased amount of cells present in the periodontally affected tissues, indicating that continuous oxidative stress which occurred in these structure affected the antioxidant pattern of the tissue. Show more

Keywords: VEGF, MVD, oxidative stress, gingivitis

Citation: BioFactors, vol. 25, no. 1-4, pp. 213-217, 2005

Authors: Singh, R.B. | Niaz, M.A. | Kumar, Adarsh | Sindberg, C.D. | Moesgaard, S. | Littarru, G.P.

Article Type: Research Article

Abstract: Introduction: The effect of various dosages and dose strategies of oral coenzyme Q_{10} (Q_{10} ) 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 × 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. Show more

Keywords: Dose strategy, Q_{10} formulations, uptake, antioxidant, oxidative stress

Citation: BioFactors, vol. 25, no. 1-4, pp. 219-224, 2005

Authors: Kalpravidh, Ruchaneekorn W. | Wichit, Angkana | Siritanaratkul, Noppadol | Fucharoen, Suthat

Article Type: Research Article

Abstract: Thalassemia is a group of genetic disorders resulting from different mutations in the globin gene complex and leading to an imbalance in globin synthesis. Unmatched globin chains are less stable and susceptible to oxidation. Patients with β-thalassemia/HbE are prone to increased oxidative stress as indicated by increased lipid peroxidation product, malondialdehyde (MDA), partly because of the presence of iron in the form of heme and hemichromes released from excess globin chains and excess iron …deposition in various tissues. The level of antioxidant such as glutathione is markedly decreased while activities of antioxidant enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) are increased. We have recently found that the levels of coenzyme Q_{10} (CoQ_{10}) are also very low in thalassemia. We therefore evaluated the oxidative stress and the antioxidants in these patients before and after supplementation with 100 mg CoQ_{10} daily for 6 months. The results showed that the plasma level of CoQ_{10} significantly increased and the oxidative stress decreased as the level of MDA declined. The administration of CoQ_{10} led to significant improvement of biochemical parameters of antioxidant enzymes. The antioxidant supplementation will be beneficial for thalassemia patients as adjunct therapy to increase their quality of life. Show more

Keywords: β-thalassemia/Hb E, oxidative stress, antioxidant, coenzyme Q_{10}

Citation: BioFactors, vol. 25, no. 1-4, pp. 225-234, 2005

Authors: Gvozdjáková, Anna | Kucharská, Jarmila | Bartkovjaková, Mária | Gazdíková, Katarína | Gazdík, Františ}ek

Article Type: Research Article

Abstract: Bronchial asthma is a chronic inflammatory disease of respiratory system, with disturbances in the dynamic balance of oxidant-antioxidant capacity of the lungs. Long-term administration of corticosteroids has been shown to result in mitochondrial dysfunction and oxidative damage of mitochondrial and nuclear DNAs. We previously documented decreased coenzyme Q_{10} (CoQ_{10}) and α-tocopherol concentrations in plasma and blood in corticosteroid-dependent bronchial asthma patients. In the present study we demonstrate that …CoQ_{10} supplementation reduces the dosage of corticosteroids in these patients. Patients and methods: This was an open, cross-over, randomized clinical study with 41 bronchial asthma patients (13 males, 28 females), ages 25–50 years. All patients suffered from persistent mild to moderate asthma. The patients were divided into two groups, one group receiving standard antiasthmatic therapy and clinically stabilized, and the second group receiving, in addition, antioxidants consisting of CoQ_{10} as Q-Gel® (120 mg) + 400 mg α-tocopherol + 250 mg vitamin C a day. The groups were crossed over at 16 weeks for a total duration of 32 weeks. Results and conclusions: Data show that patients with corticosteroid-dependent bronchial asthma have low plasma CoQ_{10} concentrations that may contribute to their antioxidant imbalance and oxidative stress. A reduction in the dosage of corticosteroids required by the patients following antioxidant supplementation was observed, indicating lower incidence of potential adverse effects of the drugs, decreased oxidative stress. This study also demonstrates the significant uptake of CoQ_{10} by lung tissue in a rat model using hydrosoluble CoQ_{10} (Q-Gel®). Show more

Keywords: Bronchial asthma, corticosteroids, coenzyme Q_{10}, oxidative stress, DNA

Citation: BioFactors, vol. 25, no. 1-4, pp. 235-240, 2005

Authors: Passi, S. | Cataudella, S. | Tiano, L. | Littarru, G.P.

Article Type: Research Article

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°C or −80°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°C and −80°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°C and −80°C appeared to be degraded after 6 and 12 months were ubiquinol and vitamin C. As expected their degradation was higher at −30°C than at −80°C. In fact the average decrease for ubiquinol at −80°C was 42% at 6 and 12 months respectively, whereas at −30°C the decrease was 61% and 87% For vitamin C the average decrease at −80°C was 36% and 67% at 6 and 12 months respectively, and at −30°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. Show more

Keywords: Mediterranean fish, ubiquinol, ubiquinone, vitamin E, vitamin C, glutathione, enzymatic antioxidants, n-3 fatty acids, TBARS, protein carbonyls, 8OHdG

Citation: BioFactors, vol. 25, no. 1-4, pp. 241-254, 2005

Authors: Afzal, M. | Safer, A. Majeed | Al-Bloushi, Shaima

Article Type: Research Article

Abstract: Green tea (Camellia sinensis), and CoQ_9 when given to Wistar rats produced a partial reversal on reserpine induced oxidative stress and liver damage. Green tea, with its abundant polyphenol (-)Epigallocatechin 3-gallate (ECGC) and other catechins, is known for its antioxidative characteristics influencing lipid metabolism. Ubiquinone, abundant in heart muscle, is also a potent antioxidant with known effects in numerous pathologies. However the combined effect of ECGC and ubiquninone has not …been reported. In the present study we found that green tea extract, when given in combination with CoQ_9 to Wistar rats subjected to oxidative stress, showed a statistically significant antioxidative effect. Liver cholesterol level in rats receiving combination treatment was also significantly lower than control or rats receiving green tea extract alone. Reserpine induced liver damage in Wister rats was also partially reversed by a treatment of green tea extract when combined with CoQ_9 . These results may have important clinical implications and may be extrapolated for the treatment of patients suffering from liver damage due to hepatitis B/C or liver cirrhosis. Show more

Keywords: Green tea, Camellia sinensis, oolong, ubiquinone, CoQ_9, antioxidative

Citation: BioFactors, vol. 25, no. 1-4, pp. 255-259, 2005

Article Type: Other

Citation: BioFactors, vol. 25, no. 1-4, pp. 261-261, 2005