Hormonal and metabolic evaluation in Down's syndrome: preliminary evidence for TSH dysregulation in hyperthyrotropinemic patients.
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Adolescent↗
Biomedical subjects
G P Littarru
Publications and source records attributed to G P Littarru.
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.
Antioxidants↗
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.
Adrenal Gland Diseases↗
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.
Aged↗
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.
Absorption↗
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.
Animals↗
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.
Adult↗
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.
Cell Survival↗
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.
Alleles↗
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.
Coenzymes↗
Oxidative response and membrane modification of diabetic platelets challenged with PAF.
Alterations in the functional activities of platelets (PLT) in type I diabetes have been widely observed. These changes play a key role in the development of cardiovascular complications in diabetes. Various functional activities of PLT are the result of the interaction of numerous stimuli with PLT plasma membrane. This study was designed to evaluate the oxidative response and membrane modifications of diabetic PLT stimulated by platelet activating factor (PAF). The oxidative response was assessed by employing luminol- and lucigenin-amplified chemiluminescence. Luminol-amplified chemiluminescence is sensitive to the release of hydrogen peroxide whereas lucigenin-amplified chemiluminescence is sensitive to the production of superoxide anion. Membrane fluidity and polarity were studied using fluorescence spectroscopy. Membrane fluidity was investigated by measuring steady-state fluorescence anisotropy of 1-[4-trimethylammonium-phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and membrane polarity was studied by measuring the steady-state fluorescence emission and excitation spectra of 2-dimethylamino[6-lauroyl]-naphthalene (Laurdan). The diabetic group consisted of 20 type I diabetic children with good metabolic control. Our results show a significant decrease in the luminol- and lucigenin-amplified chemiluminescence of PAF stimulated PLT in the diabetic group with respect to controls. These data indicate a decrement in the release of reactive oxygen species by diabetic PLT. We observed a significant increase in steady-state fluorescence anisotropy of diabetic PLT membrane that reflects a decrease in membrane fluidity. Laurdan showed a blue shift of the fluorescence emission and excitation spectra in diabetic PLT with respect to the control group, indicating a decrease in membrane polarity. The addition of PAF to PLT induced a red shift of Laurdan spectra in both groups, indicating an increase in membrane polarity. Our study [table: see text] demonstrates an altered oxidative response to PAF stimulation of diabetic PLT, probably due to altered generation or handling of reactive oxygen species, and alterations in the physico-chemical properties of the plasma membrane which could influence various functional activities of PLT.
Acridines↗
Plasma membrane polarity of polymorphonuclear leucocytes from children with primary ciliary dyskinesia.
BACKGROUND: Polymorphonuclear leucocytes (PMN) from subjects with primary ciliary dyskinesia (PCD) can have abnormal locomotory systems. The locomotory activity of PMN is the result of biochemical events mediated by the plasma membrane. In this study we investigated plasma membrane polarity of PMN from children with PCD. DESIGN: Membrane polarity was studied in 11 children with PCD and in healthy controls by measuring the steady-state fluorescence excitation and emission spectra of 2-dimethylamino[6-lauroyl]naphthalene (Laurdan), which is known to be incorporated at the hydrophobic-hydrophilic interface of the bilayer, displaying spectral sensitivity to the polarity of its surroundings. Laurdan shows a marked steady-state emission red shift in polar solvents, with respect to nonpolar solvents. Moreover, the effect of the microtubule disassembling agent colchicine on PMN membrane polarity was evaluated. RESULT: Our results show a red shift of the fluorescence excitation and emission spectra of Laurdan in PMN from the PCD group with respect to the control group. These data indicate an increase in membrane polarity of PMN from the PCD group. Treatment of PMN with colchicine induced a red shift in the Laurdan excitation and emission spectra with the same trend observed in PMN from the PCD group. CONCLUSION: PMN from children with PCD are characterized by an increased plasma membrane polarity. These changes could be the basis of the modifications in the locomotory activities of PMN. The observed alterations may be attributed to abnormalities in the cytoskeleton.
2-Naphthylamine↗
Evaluation of ischemia-reperfusion damage during coronary angioplasty. Electrocardiographic assessment and biochemical modifications in blood from the coronary sinus.
BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) constitutes a clinical model of reperfusion following a short period of ischemia connected to balloon inflation during the procedure. During the procedure some ischemic damage and oxidative injury related to free radical attack might occur. In the present study we investigated the extent of ischemic damage and some biochemical indexes of reperfusion damage in patients undergoing PTCA. METHODS: Twenty-five patients who underwent PTCA because of angiographically detected occlusion of the coronary artery were enrolled. Balloon inflation lasted from 30 to 60 s. ECG changes were monitored throughout the procedure and blood samples were taken from the coronary artery and coronary sinus before balloon inflation, and again from coronary sinus at the peak of ischemia, 2 and 10 min after reperfusion. RESULTS: During PTCA procedure angina pectoris appeared in 62.7% of patients, whereas ST-segment elevation was present in 87% of patients, regressing completely after balloon deflation. Plasma malonyldialdehyde, an index of lipid peroxidation, did not change; coenzyme Q10 (in its oxidized and reduced forms), vitamin E and beta-carotene were also unchanged. Total antioxidant capacity and uric acid decreased upon reperfusion. CONCLUSIONS: Myocardial ischemia occurring during balloon inflation is brief and regresses completely after balloon deflation. Reperfusion following a short period of acute ischemia such as in PTCA does not constitute an oxidative event detectable through a common marker of lipid peroxidation nor does it alter the concentration of lipophilic antioxidants. It only lowers hydrosoluble antioxidants therefore representing a mild oxidative insult.
Aged↗
Distribution of antioxidants among blood components and lipoproteins: significance of lipids/CoQ10 ratio as a possible marker of increased risk for atherosclerosis.
Total CoQ10 levels were evaluated in whole blood and in plasma obtained from a group of 83 healthy donors. Extraction with light petroleum ether/methanol was more efficient, for whole blood, than the extraction which is often used for plasma and serum, i.e., ethanol hexane. An excellent correlation was present between plasma CoQ10 and whole blood CoQ10. CoQ10 is mainly associated with plasma rather than with cellular components. Positive, significant correlations were found between the LDL-chol/CoQ10 ratio and the total-chol/HDL-chol ratio, which is usually considered a risk factor for atherosclerosis. The proportion of CoQ10 carried by LDL was 58 +/- 10%, while the amount carried by HDL was 26 +/- 8%. In VLDL + IDL CoQ10 was 16 +/- 8%. The content of CoQ10 in single classes of lipoproteins is strictly correlated with CoQ10 plasma concentration. In a parallel study conducted on a population of diabetic patients (one IDDM group and one NIDDM) CoQ10 plasma levels were generally higher compared to the control group, also when normalised to total cholesterol. In particular the LDL fraction showed a CoQ10/chol ratio higher in NIDDM but not in IDDM patients, compared to controls. The CoQ10/triglycerides ratio was lower in NIDDM respect to controls and even lower in IDDM patients.
Aged↗
Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes.
Ubiquinol-10, the reduced form of coenzyme Q10, is a powerful antioxidant in plasma and lipoproteins. It has been suggested that endogenous ubiquinol-10 also exerts a protective role even towards DNA oxidation mediated by lipid peroxidation. Even though the antioxidant activity of coenzyme Q10 is mainly ascribed to ubiquinol-10, a role for ubiquinone-10 (the oxidized form), has been suggested not only if appropriate reducing systems are present. To investigate whether the concentration of ubiquinol-10 or ubiquinone-10 affects the extent of DNA damage induced by H2O2, we supplemented in vitro human lymphocytes with both forms of coenzyme Q10 and evaluated the DNA strand breaks by Comet assay. The exposure of lymphocytes to 100 microM H2O2 resulted in rapid decrease of cellular ubiquinol-10 content both in ubiquinol-10-enriched and in control cells, whereas alpha-tocopherol and beta-carotene concentration were unchanged. After 30 min from H2O2 exposure, the amount of DNA strand breaks was lower and cells' viability was significantly higher in ubiquinol-10-enriched cells compared with control cells. A similar trend was observed in ubiquinone-10-enriched lymphocytes when compared with control cells. Our experiments suggest that coenzyme Q10 in vitro supplementation enhances DNA resistance towards H2O2-induced oxidation, but it doesn't inhibit directly DNA strand break formation.
Adult↗
Antioxidant status and dialysis: plasma and saliva antioxidant activity in patients with fluctuating urate levels.
The present study is concerned with the influence of processes occurring during dialysis on the antioxidant capacity of plasma and saliva. The biological fluids were also tested for uric acid and total protein content. Before hemodialysis, plasma antioxidant status of hemodialyzed patients appears slightly higher than the corresponding status in normal subjects; after hemodialysis it is found unchanged. The result can be explained by a balance between a reduction in uric acid plasma content, due to the dialytic procedure, and an increase in protein content, possibly due to a dialysis-related hemoconcentration. Moreover, pre-dialysis total antioxidant capacity of whole saliva samples is higher than in healthy individuals and drastically decreases towards normal values following dialytic procedure. Our data indicate a certain concentration of the uric acid in the saliva of hemodialyzed patients and evidence that both total protein concentration and uric acid level show a good correlation with saliva total antioxidant capacity, suggesting that proteins are major antioxidants of this fluid. Further observations are needed to assess whether this improved saliva antioxidant ability has any consequence on the periodontal conditions of hemodialyzed subjects.
Adult↗
Dietary restriction affects antioxidant levels in rat liver mitochondria during ageing.
Six experimental groups of young (7-month-old) and aged (24-32-month-old) rats, underwent different dietary manipulations (i.e. dietary restriction and/or a vitamin E-depleted diet), and their liver mitochondria were assayed for several antioxidants and peroxidation markers. Glutathione levels were affected both by age and dietary treatment. Coenzyme Q9 and C0Q10 showed the highest levels in the oldest rats where ageing, as well as other oxidative stresses, could induce ubiquinone biosynthesis.
Aging↗
Metabolic and antioxidant markers in the plasma of sportsmen from a Mediterranean town performing non-agonistic activity.
It has been widely indicated that several pathological conditions depend upon concomitant risk factors rather than a unique one and that also the putative protective factors do not act alone. For these reasons it could be useful to consider subjects that present sufficiently homogeneous lifestyles (i.e. nutrition and physical activity). We carried out an investigation in a free-living community in order to clarify the possible correlations and differences among plasma metabolic and antioxidant markers in non-agonistic athletes. When subjects were divided in two main groups according to age (35-44 and 45-54 years) without considering the activity they performed, Duncan's analysis of variance revealed that they showed similar characteristics and only triglyceride levels were different. A clear negative correlation was found between vitamin E and VO2max in both age groups, a negative correlation was also found between CoQ10 and VO2max in the younger subjects and finally CoQ10 and vitamin E were also positively correlated in this first group. It appears, therefore, that people with a higher aerobic capacity have lower circulating levels of antioxidants.
Adult↗