Vitamin MK-7 enhances vitamin D3-induced osteogenesis in hMSCs: modulation of key effectors in mineralization and vascularization.

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

Coenzyme Q10 supplementation in infertile men with low-grade varicocele: an open, uncontrolled pilot study.

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

Relationship between plasma antioxidants and thyroid hormones in chronic obstructive pulmonary disease.

BACKGROUND: A low-T3 syndrome is observed in chronic diseases, but its treatment is still debated. Chronic obstructive pulmonary disease (COPD) has not been conclusively studied under this aspect. COPD is a complex condition, which cannot be considered a lung-related disorder, but rather a systemic disease also associated to increased oxidative stress. We evaluated thyroid hormones and antioxidant systems, the lipophilic Coenzyme Q10 (CoQ10) and total antioxidant capacity (TAC) in COPD patients to reveal the presence of a low-T3 syndrome in COPD and investigate the correlation between thyroid hormones, lung function parameters and antioxidants. METHODS: We studied: 32 COPD patients and 45 controls, evaluating thyrotropin (TSH), free-triiodotyronine (fT3), free-tetraiodotyronine (fT4), CoQ10 (also corrected for cholesterol) and TAC. CoQ10 was assayed by HPLC; TAC by the metmyoglobin-ABTS method and expressed as latency time (LAG) in radical species appearance. RESULTS: We found significantly lower LAG values, fT3 and fT4 levels and significantly higher TSH in COPD patients vs. controls. LAG values significantly correlated with fT3 concentration. 12 out of 32 patients exhibited fT3 levels lower than normal range. So we divided COPD patients in 2 groups on the basis of the fT3 concentration (normal fT3 COPD and low fT3 COPD). We observed lower LAG values in normal fT3-COPD, compared to healthy subjects, with a further significant reduction in low fT3-COPD patients. Moreover higher TSH concentration was present in normal fT3-COPD, compared to healthy subjects, with a further significant increase in low fT3-COPD patients. CoQ10/cholesterol ratio was higher in low fT3-COPD vs. normal fT3-COPD, with a nearly significant difference. CONCLUSIONS: These data seem to indicate an increased oxidative stress in low fT3-COPD and a role of fT3 in modulating antioxidant systems. However low fT3 levels are joined to metabolic indexes of true hypothyroidism, suggesting that elevated CoQ10 expresses a reduced tissue utilization. These data might suggest the need of thyroid replacement therapy in such a condition.

Reference gene validation for qPCR on normoxia- and hypoxia-cultured human dermal fibroblasts exposed to UVA: is ß-actin a reliable normalizer for photoaging studies?

Data normalization of gene expression on human dermal fibroblasts (HDF) exposed to UVA has commonly been done using either GAPDH or ß-actin as reference genes without any validation of their expression stability. Since this aspect, important for accurate normalization, has been overlooked, we aimed to establish a suitable set of reference genes for studies on UVA-treated HDF cultured under both standard atmospheric oxygen tension (normoxia, 21%) and under a physiological, low oxygen tension for these cells (hypoxia, 5%). The stability of six commonly used reference genes was assessed using the geNorm and NormFinder softwares subsequent to reverse-transcription quantitative real-time PCR (RT-qPCR). GAPDH/SDHA were found to be the most stable genes under normoxia, while SDHA/TBP or HPRT1/ß2M were the most stable ones under hypoxia in HDF exposed to 18 J/cm(2) UVA. ß-Actin was always the most unstable reference gene. To emphasize the importance of selecting the most stably expressed reference genes for obtaining reliable results, mRNA expression levels of MMP-1 and COL1A1 were analyzed vs the best reference genes and the worst one. These reference genes are hence recommended for future qPCR analyses in studies concerning photo-damage on UVA-treated HDF.

Effect of Coenzyme Q10 in mitigating oxidative DNA damage in Down syndrome patients, a double blind randomized controlled trial.

Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with a complex phenotype. Oxidative stress is known to play a major role in this pathology both due to genetic and epigenetic factors, suggesting that oxidative imbalance contributes to the clinical manifestation of DS. In particular, the implications of oxidative DNA damage in Down syndrome has been linked with neurodegeneration. Here we report the results of a double blind controlled trial aimed at investigating the protective effect of Coenzyme Q(10) on DNA oxidation in this clinical setting using the single cell gel electrophoresis technique.

Hormones and antioxidant systems: role of pituitary and pituitary-dependent axes.

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

Evaluation of antioxidant systems in pituitary-adrenal axis diseases.

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

Coenzyme Q10 and male infertility.

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

Coenzyme Q10 and oxidative imbalance in Down syndrome: biochemical and clinical aspects.

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

In vitro photostability and photoprotection studies of a novel 'multi-active' UV-absorber.

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

Seminal antioxidants in humans: preoperative and postoperative evaluation of coenzyme Q10 in varicocele patients.

Coenzyme Q10 in seminal fluid shows a direct correlation with seminal parameters except in patients with varicocele. To evaluate whether surgical treatment of varicocele could revert CoQ10 abnormalities, we have studied CoQ10 distribution in thirty-three VAR patients, before and 6-8 months after varicocelectomy, twenty patients with idiopathic oligozoospermia, eleven with isolated asthenozoospermia and sixteen normal fertile men. CoQ10 was assayed in total seminal fluid, plasma or cell pellet by HPLC. A significantly higher CoQ10 proportion in seminal plasma in VAR vs. controls (mean +/- SEM: 61.68 +/- 2.41 vs. 41.60 +/- 1.99%, respectively) was present; total CoQ10 correlated with sperm motility in controls, but not in VAR; an inverse correlation between cellular CoQ10 and motility was present in VAR, but not in controls. Postoperatively, a partial reversion was observed, since the plasma-to-total CoQ10 ratio decreased, but the correlation between total CoQ10 and motility was not restored. On the contrary, the peculiar correlation between cellular CoQ10 and motility was no more detectable in postoperative VAR patients. A partial postoperative reversal of abnormalities in CoQ10 distribution and correlation with seminal parameters was therefore present. As seminal plasma CoQ10 reflects an interchange between intracellular and extracellular compartments, its different distribution could cause a greater sensitivity to peroxidative damage and a reduced utilization for energetic purpose.

An update of Coenzyme Q10 implications in male infertility: biochemical and therapeutic aspects.

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

Coenzyme Q10 evaluation in pituitary-adrenal axis disease: preliminary data.

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

Relationships between plasma CoQ10 levels and thyroid hormones in chronic obstructive pulmonary disease.

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

Effect on absorption and oxidative stress of different oral Coenzyme Q10 dosages and intake strategy in healthy men.

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

Dynamics of lipid oxidation and antioxidant depletion in Mediterranean fish stored at different temperatures.

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

Effect of UV-C mediated oxidative stress in leukemia cell lines and its relation to ubiquinone content.

UV-C radiation is able to impair cellular functions by directly damaging DNA, and by inducing an increased formation of reactive oxygen species that leads to a condition of oxidative stress. In this study we evaluated different responses to UV insult of two leukemia cell lines, HL-60 and Raji, and the relationship with their CoQ10 content. DNA damage was monitored by means of the alkaline single cell gel electrophoresis (Comet assay); intracellular levels of ROS, mitochondrial depolarization and cell viability was measured by flow cytometry. Raji cells appeared more resistant to the UV insult; moreover, they did not show any increase in ROS content and the extent of mitochondrial depolarisation was much lower than in HL 60 cell line. Raji cells also contained significantly higher levels of CoQ10 and their ability to incorporate and to reduce exogenous CoQ10 added to the culture medium was remarkably elevated compared with HL 60.

Coenzyme Q10, antioxidant status and ApoE isoforms.

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

Coenzyme Q10 levels in idiopathic and varicocele-associated asthenozoospermia.

Levels of coenzyme Q10 (CoQ10) and of its reduced and oxidized forms (ubiquinol, QH2, and ubiquinone, Qox) have been determined in sperm cells and seminal plasma of idiopathic (IDA) and varicocele-associated (VARA) asthenozoospermic patients and of controls. The results have shown significantly lower levels of coenzyme Q10 and of its reduced form, QH2, in semen samples from patients with asthenospermia; furthermore, the coenzyme Q10 content was mainly associated with spermatozoa. Interestingly, sperm cells from IDA patients exhibited significantly lower levels of CoQ10 and QH2 when compared to VARA ones. The QH2/Qox ratio was significantly lower in sperm cells from IDA patients and in seminal plasma from IDA and VARA patients when compared with the control group. The present data suggest that the QH2/Qox ratio may be an index of oxidative stress and its reduction, a risk factor for semen quality. Therefore, the present data could suggest that sperm cells, characterized by low motility and abnormal morphology, have low levels of coenzyme Q10. As a consequence, they could be less capable in dealing with oxidative stress which could lead to a reduced QH2/Qox ratio. Furthermore, the significantly lower levels of CoQ10 and QH2 levels in sperm cells from IDA patients, when compared to VARA ones, enable us to hypothesize a pathogenetic role of antioxidant impairment, at least as a cofactor, in idiopathic forms of asthenozoospermia.