Biofactors - Volume 25, issue 1-4

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