bluuebunny/crossref_metadata_2025 huggingface dataset:
C. elegansknockouts in ubiquinone biosynthesis genes result in different phenotypes during larval development
Authors: Gavilán ÁNgela , Asencio Claudio , Cabello Juan , Rodríguez‐Aguilera Juan C. , Schnabel Ralf , Navas PlÁCido
Published: December 2008

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‐respiringpetiteyeast. In C. elegans,coq‐7/clk‐1but notcoq‐3mutants 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 thesecoqmutants.

These phenomena suggest that coenzyme Q mutants unable to synthesize this molecule develop a deleterious phenotype leading to lethality. On the contrary, phenotype ofC. elegans coq‐7/clk‐1mutants 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.
NAD+/NADH and/or CoQ/CoQH2 ratios from plasma membrane electron transport may determine ceramide and sphingosine‐1‐phosphate levels accompanying G1 arrest and apoptosis
Authors: Luca Thomas De , Morré Dorothy M. , Zhao Haiyun , James Morré D.
Published: December 2008

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 Q10 (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 Q10 (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 G1 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 G1 arrest (increase in ceramide) and apoptosis (loss of sphingosine‐1‐phosphate). As such, the findings provide potential links between coenzyme Q10‐mediated plasma membrane electron transport and the anticancer action of several clinically‐relevant anticancer agents.
Coenzyme Q10 in maternal plasma and milk throughout early lactation
Authors: Niklowitz Petra , Menke Thomas , Giffei JÖRg , Andler Werner
Published: December 2008

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.
Ubiquinol and the papaverine derivative caroverine prevent the expression of tumour‐ promoting factors in adenoma and carcinoma colon cancer cells induced by dietary fat
Authors: Nohl Hans , Rohr‐Udilova Natalia , Gille Lars , Bieberschulte Werner , Jurek Daniela , Marian Brigitte , Schulte‐Hermann Rolf
Published: December 2008

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.
Coenzyme Q10 protects SHSY5Y neuronal cells from beta amyloid toxicity and oxygen‐glucose deprivation by inhibiting the opening of the mitochondrial permeability transition pore
Authors: Li Geng , Zou Liang‐Yu , Cao Chun‐Mei , Yang Edward S.
Published: December 2008

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.
Muscle coenzyme Q10 concentrations in patients with probable and definite diagnosis of respiratory chain disorders
Authors: Montero R. , Artuch R. , Briones P. , Nascimento A. , García‐Cazorla A. , Vilaseca M.A. , Śnchez‐Alćzar J.A. , Navas P. , Montoya J. , Pineda M.
Published: December 2008

Coenzyme Q10 (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.
A metabolic approach to the treatment of dilated cardiomyopathy in BIO T0–2 cardiomyopathic Syrian hamsters
Authors: Mancinelli Rino , Vargiu Romina , Cappai Antonello , Floris Giuseppe , Fraschini Matteo , Faa Gavino
Published: December 2008

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 Q10 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.
Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure
Authors: Belardinelli Romualdo , Muçaj Andi , Lacalaprice Francesca , Solenghi Maridia , Principi Federica , Tiano Luca , Littarru Gian Paolo
Published: December 2008

Background: There is evidence that plasma CoQ10 levels decrease in patients with advanced chronic heart failure (CHF).

Objective: To investigate whether oral CoQ10 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 CoQ10 (100 mg tid) and to placebo for 4 weeks, respectively.

Results: CoQ10 supplementation resulted in a threefold increase in plasma CoQ10 level (P<0.0001 vs placebo). Systolic wall thickening score index (SWTI) was improved both at rest and peak dobutamine stress echo after CoQ10 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/m2 to 45 mL/m2, 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 CoQ10 levels (r=−0.52, P<0.005). Peak VO2 was also improved after CoQ10 as compared with placebo (+13%, <0.005). No side effects were reported with CoQ10.

Conclusions: Oral CoQ10 improves LV contractility in CHF without any side effects. This improvement is associated with an enhanced functional capacity.
Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation
Authors: Langsjoen Peter H. , Langsjoen Jens O. , Langsjoen Alena M. , Lucas Lindsay A.
Published: December 2008

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 CoQ10 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 CoQ10. We saw no adverse consequences from statin discontinuation.
Coenzyme Q10 is increased in placenta and cord blood during preeclampsia
Authors: Teran Enrique , Vivero Sandra , Racines‐Orbe Marcia , Castellanos Alberto , Chuncha Galo , Enriquez Galo , Moya Walter
Published: December 2008

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 Q10 (CoQ10) 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 Q10 were measured by high performance liquid chromatography (HPLC). Plasma coenzyme Q10 levels were significantly higher in normal pregnant women than in women with preeclampsia. CoQ10content 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 CoQ10 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 CoQ10 in preeclampsia that might bear deep physiopathological significance and deserve to be further elucidated.
Placental CoQ10 levels in HELLP syndrome
Authors: Giannubilo Stefano R. , Tranquilli Andrea L. , Santolini Cristina , Prinicipi Federica , Mancinelli Romina , Littarru Gian Paolo
Published: December 2008

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 Q10 (CoQ10), 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 CoQ10 concentration were thereafter analysed. CoQ10 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 CoQ10 /protein ratio. A significant positive correlation was also present between CoQ10/protein ratio and Apgar at 1st and 5th minute as well as between CoQ10/protein ratio and the median cerebral artery pulsatility index. The increase in placental CoQ10 in this syndrome might derive from a compensatory mechanism in a situation of increased oxidative stress.
An update of Coenzyme Q10 implications in male infertility: Biochemical and therapeutic aspects
Authors: Mancini A. , De Marinis L. , Littarru G. P. , Balercia G.
Published: December 2008

This review is focused upon the role of coenzyme Q10 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 Q10 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 CoQ10 in seminal fluid was also investigated.

After the first in vitro experiments CoQ10 was administered to a group of idiopathic asthenozoospermic infertile patients. Seminal analysis showed a significant increase of CoQ10 both in seminal plasma and in sperm cells, together with an improvement in sperm motility.

The increased concentration of CoQ10 in seminal plasma and sperm cells, the improvement of semen kinetic features after treatment, and the evidence of a direct correlation between CoQ10 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.
CoQ10 supplementation elevates the epidermal CoQ10 level in adult hairless mice
Authors: Ashida Yutaka , Yamanishi Haruyo , Terada Takatomo , Oota Norihito , Sekine Kyoichi , Watabe Kazuo
Published: December 2008

We have already shown that prolonged supplementation of CoQ10 in humans reduces the wrinkle area rate and wrinkle volume per unit area in the corner of the eye. CoQ10 supplementation is known to increase the CoQ10 level in serum and in many organs; however, the level of CoQ10 in skin has not yet been fully investigated yet. We examined whether CoQ10 intake elevates the CoQ10 and CoQ9 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 CoQ9 and CoQ10 in the tissues. CoQ10 (0, 1, 100 mg/kg p.o.) was administered daily for 2 weeks. CoQ10 supplementation of 100 mg/kg increased the serum and epidermal CoQ10 levels significantly, but did not increase the CoQ10 levels in either dermis or other organs. In conclusion, we showed that CoQ10 intake elevates the epidermal CoQ10 level, which may be a prerequisite to the reduction of wrinkles and other benefits related to the potent antioxidant and energizing effects of CoQ10 in skin.
Stimulation of skin's energy metabolism provides multiple benefits for mature human skin
Authors: Blatt T. , Lenz H. , Koop U. , Jaspers S. , Weber T. , Mummert C. , Wittern K.‐P. , Stäb F. , Wenck H.
Published: December 2008

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.
Assessment of DNA damage in Down Syndrome patients by means of a new, optimised single cell gel electrophoresis technique
Authors: Tiano Luca , Littarru Gian Paolo , Principi Federica , Orlandi Marco , Santoro Lucia , Carnevali Paola , Gabrielli Orazio
Published: December 2008

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.
Coenzyme Q10 evaluation in pituitary‐adrenal axis disease: Preliminary data
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.
Published: December 2008

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.
Relationships between plasma CoQ10 levels and thyroid hormones in chronic obstructive pulmonary disease
Authors: Mancini A. , Corbo G. M. , Gaballo A. , Valente S. , Gigliotti P. , Cimino V. , De Marinis L. , Principi F. , Littarru G.P.
Published: December 2008

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.
Estimation of plasma and saliva levels of coenzyme Q10 and influence of oral supplementation
Authors: Sekine K. , Ota N. , Nishii M. , Uetake T. , Shimadzu M.
Published: December 2008

Coenzyme Q10 (CoQ10) 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 CoQ10 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 CoQ10 levels throughout the day. A good correlation was obtained by colleting parotid gland saliva at times between meals. The mean saliva CoQ10 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, CoQ10 was analyzed in plasma and parotid gland saliva from 20 healthy volunteers supplemented daily with 100 mg of CoQ10 for the first week and 200 mg for the second. The plasma CoQ10 levels of all volunteers increased to different extents in accordance with the CoQ10 daily intake and the corresponding change in saliva showed almost the same trend.
Antioxidant status (CoQ10 and Vit. E levels) and immunohistochemical analysis of soft tissues in periodontal diseases
Authors: Battino Maurizio , Bompadre Stefano , Politi Alessia , Fioroni Massimiliano , Rubini Corrado , Bullon Pedro
Published: December 2008

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 CoQ10 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 CoQ10 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.
Effect on absorption and oxidative stress of different oral Coenzyme Q10dosages and intake strategy in healthy men
Authors: Singh R. B. , Niaz M. A. , Kumar Adarsh , Sindberg C. D. , Moesgaard S. , Littarru G. P.
Published: December 2008

Introduction: The effect of various dosages and dose strategies of oral coenzyme Q10(Q10) administration on serum Q10concentration 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 Q10soft oil capsules (Myoqinon 100 mg, Pharma Nord, Denmark) or crystalline 100 mg Q10powder 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 Q10administration. 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 Q10(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 Q10. Q10dissolved in an oil matrix was more effective than the same amount of crystalline Q10in raising Q10serum levels. 200 mg of oil/soft gel formulation of Q10caused a larger increase in Q10serum levels than did 100 mg. Divided dosages (2 × 100 mg) of Q10caused a larger increase in serum levels of Q10than 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 Q10levels which may be due to vegetarian diets. Further studies in larger number of subjects would be necessary to confirm our findings.
Effect of coenzyme Q10 as an antioxidant in β‐thalassemia/Hb E patients
Authors: Kalpravidh Ruchaneekorn W. , Wichit Angkana , Siritanaratkul Noppadol , Fucharoen Suthat
Published: December 2008

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 Q10 (CoQ10) 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 CoQ10 daily for 6 months. The results showed that the plasma level of CoQ10 significantly increased and the oxidative stress decreased as the level of MDA declined. The administration of CoQ10 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.
Coenzyme Q10 supplementation reduces corticosteroids dosage in patients with bronchial asthma
Authors: Gvozdjáková Anna , Kucharská Jarmila , Bartkovjaková MÁRia , Gazdíková KatarÍNa , Gazdík FrantiŠEk
Published: December 2008

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 Q10 (CoQ10) and α‐tocopherol concentrations in plasma and blood in corticosteroid‐dependent bronchial asthma patients. In the present study we demonstrate that CoQ10 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 CoQ10 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 CoQ10 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 CoQ10 by lung tissue in a rat model using hydrosoluble CoQ10 (Q‐Gel®).
Dynamics of lipid oxidation and antioxidant depletion in Mediterranean fish stored at different temperatures
Authors: Passi S. , Cataudella S. , Tiano L. , Littarru G.P.
Published: December 2008

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.
CoQ9 potentiates green tea antioxidant activities in Wistar rats
Authors: Afzal M. , Safer A. Majeed , Al‐Bloushi Shaima
Published: December 2008

Green tea (Camellia sinensis), and CoQ9 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 CoQ9 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 CoQ9. 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.
6‐Gingerol prevents cisplatin‐induced acute renal failure in rats
Authors: Kuhad Anurag , Tirkey Naveen , Pilkhwal Sangeeta , Chopra Kanwaljit
Published: December 2008

Background: Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that enhanced oxidative stress caused by oxygen‐centered free radicals may contribute to the pathogenesis of cisplatin‐induced acute renal failure. 6‐Gingerol is claimed to be a potent antioxidant. The present study was performed to explore the renoprotective potential of 6‐gingerol on cisplatin‐induced oxidative stress and renal dysfunction.

Methods: 6‐Gingerol in dosages of 12.5, 25, 50 mg/kg was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase.

Results: A single dose of cisplatin resulted in marked renal oxidative and nitrosative stress and significantly deranged renal functions. 6‐Gingerol treatment significantly and dose‐dependently restored renal functions, reduced lipid peroxidation and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase.

Conclusions: The present study demonstrates the renoprotective potential of 6‐gingerol against cisplatin‐induced oxidative stress and renal dysfunction in rats. Hence, 6‐gingerol has a potential to be used as therapeutic adjuvant in cisplatin nephrotoxicity.
Relaxation and immunity enhancement effects of γ‐Aminobutyric acid (GABA) administration in humans
Authors: Abdou Adham M. , Higashiguchi S. , Horie K. , Kim Mujo , Hatta H. , Yokogoshi H.
Published: December 2008

The effect of orally administrated γ‐Aminobutyric acid (GABA) on relaxation and immunity during stress has been investigated in humans. Two studies were conducted. The first evaluated the effect of GABA intake by 13 subjects on their brain waves. Electroencephalograms (EEG) were obtained after 3 tests on each volunteer as follows: intake only water, GABA, or L‐theanine. After 60 minutes of administration, GABA significantly increases alpha waves and decreases beta waves compared to water or L‐theanine. These findings denote that GABA not only induces relaxation but also reduces anxiety. The second study was conducted to see the role of relaxant and anxiolytic effects of GABA intake on immunity in stressed volunteers. Eight acrophobic subjects were divided into 2 groups (placebo and GABA). All subjects were crossing a suspended bridge as a stressful stimulus. Immunoglobulin A (IgA) levels in their saliva were monitored during bridge crossing. Placebo group showed marked decrease of their IgA levels, while GABA group showed significantly higher levels. In conclusion, GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety. Moreover, GABA administration could enhance immunity under stress conditions.
Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver of diabetic mice
Authors: Kim Sung Hee , Hyun Sun Hee , Choung Se Young
Published: December 2008

Both Cinnamomi cassiae and Rhodiola rosea extracts are used as anti‐diabetic folk medicines. Recently, increased oxidative stress was shown to play an important role in the etiology and pathogenesis of diabetes mellitus and its complications. This study was designed to examine the effects of Cinnamomi cassiae and Rhodiola rosea extracts on blood glucose, lipid peroxidation, the level of reduced glutathione and its related enzymes (glutathione reductase, glutathione S‐transferase), and the activity of the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) in the liver of db/db mice.

Diabetic C57BL/Ks db/db mice were used as experimental models. Mice were divided into control (n =10), Cinnamomi cassiae (200 mg/kg/day, n = 10), and Rhodiola rosea (200 mg/kg/day, n =10) treated groups for 12 weeks of treatment. These type II diabetic mice were used to investigate the effects of Cinnamomi cassiae and Rhodiola rosea on blood glucose, reduced glutathione, glutathione reductase, glutathione S‐transferase, glutathione peroxidase, lipid peroxidation, catalase and superoxide dismutase.

Cinnamomi cassiae and Rhodiola rosea extracts significantly decreased on blood glucose, increased levels of reduced glutathione and the activities of glutathione reductase, glutathione S‐transferase, glutathione peroxidase, catalase and superoxide dismutase in the liver. Extract treatment also significantly decreased lipid peroxidation.

Cinnamomi cassiae and Rhodiola rosea extracts may be effective for correcting hyperglycemia and preventing diabetic complications.
Schisandrin B‐induced increase in cellular glutathione level and protection against oxidant injury are mediated by the enhancement of glutathione synthesis and regeneration in AML12 and H9c2 cells
Authors: Chiu Po Yee , Ko Kam Ming
Published: December 2008

Abstract. To define the relative role of reduced glutathione (GSH) synthesis and regeneration in schisandrin B (Sch B)‐induced increase in cellular GSH level and the associated cytoprotection against oxidative challenge, the effects of L‐buthionine‐[S,R]‐sulfoximine (BSO, a specific inhibitor of γ ‐glutamate cysteine ligase (GCL)) and 1,3‐bis(2‐chloroethyl)‐1‐nitrourea (BCNU, a specific inhibitor of glutathione reductase (GR)) treatments or their combined treatment were examined in control and Sch B‐treated AML12 and H9c2 cells, without and/or with menadione intoxication. Both BSO and BCNU treatments reduced cellular GSH level in AML12 and H9c2 cells, with the effect of BSO being more prominent. The GSH‐enhancing effect of Sch B was also suppressed by BSO and BCNU treatments, with the effect of the combined treatment with BSO and BCNU being semi‐additive. While Sch B treatment increased the GR but not GCL activity in AML12 and H9c2 cells, it increased the cellular cysteine level. BSO treatment also suppressed the Sch B‐induced increase in GR activity. BSO or BCNU treatment per se did not cause any detectable cytotoxic effect, as assessed by lactate dehydrogenase leakage, but the combined treatment with BSO and BCNU was cytotoxic, particularly in H9c2 cells. The cytotoxic effect of BSO and BCNU became more apparent following the menadione challenge. The cytoprotection afforded by Sch B pretreatment was partly suppressed by BSO or BCNU treatment, or completely abrogated by the combined treatment with BSO and BCNU. In conclusion, the results indicate that the cytoprotective action of Sch B is causally related to the increase in cellular GSH level, which is likely mediated by the enhancement of GSH synthesis and regeneration.
Antioxidant and antigenotoxic activities of Angelica keiskei, Oenanthe javanica and Brassica oleracea in the Salmonella mutagenicity assay and in HCT116 human colon cancer cells
Authors: Kwon Daejoong , Yoon Sun , Carter Orianna , Bailey George S. , Dashwood Roderick H.
Published: December 2008

Epidemiological studies indicate that consumption of green‐yellow vegetables rich in chlorophyll, vitamin C, vitamin E, and carotenoids reduce the risk of cancer. We sought to examine the antigenotoxic and antioxidant properties of chlorophyll‐rich methanol extracts of Angelica keiskei, Oenanthe javanica, and Brassica oleracea (kale). In the Salmonella mutagenicity assay, A. keiskei caused dose‐dependent inhibition against three heterocyclic amine mutagens in the presence of S9, O. javanica was antimutagenic only at the highest concentration in the assay (2 mg/plate), and B. oleracea showed no consistent inhibitory activity at non‐toxic levels. None of the extracts were effective against three direct‐acting mutagens in the absence of S9. Extracts of A. keiskei and, to a lesser extent O. javanica, inhibited two of the major enzymes that play a role in the metabolic activation of heterocyclic amines, based on ethoxyresorufin‐O‐deethylase and methoxyresorufin‐O‐demethylase assays in vitro. All three plant extracts were highly effective in assays which measured ferric reducing/antioxidant power, oxygen radical absorbance capacity, and Fe2+/H2O2‐mediated DNA nicking. Finally, using the ‘comet’ assay, all three plant extracts protected against H2O2‐induced genotoxic damage in human HCT116 colon cancer cells. These findings provide support for the antigenotoxic and antioxidant properties of chlorophyll‐rich extracts of A. keiskei, O. javanica, and B. oleracea, through mechanisms that include inhibition of carcinogen activation and scavenging of reactive oxygen species.