Clinical aspects of coenzyme Q10 : An update Littarru, Gian Paolo, M.D., Ph.D; Tiano, Luca, Ph.D
Nutrition (Burbank, Los Angeles County, Calif.),
03/2010, Letnik:
26, Številka:
3
Journal Article
Recenzirano
Abstract The fundamental role of coenzyme Q10 (CoQ10 ) in mitochondrial bioenergetics and its well-acknowledged antioxidant properties constitute the basis for its clinical applications, although ...some of its effects may be related to a gene induction mechanism. Cardiovascular disease is still the main field of study and the latest findings confirm a role of CoQ10 in improving endothelial function. The possible relation between CoQ10 deficiency and statin side effects is highly debated, particularly the key issue of whether CoQ10 supplementation counteracts statin myalgias. Furthermore, in cardiac patients, plasma CoQ10 was found to be an independent predictor of mortality. Studies on CoQ10 and physical exercise have confirmed its effect in improving subjective fatigue sensation and physical performance and in opposing exercise-related damage. In the field of mitochondrial myopathies, primary CoQ10 deficiencies have been identified, involving different genes of the CoQ10 biosynthetic pathway; some of these conditions were found to be highly responsive to CoQ10 administration. The initial observations of CoQ10 effects in Parkinson's and Huntington's diseases have been extended to Friedreich's ataxia, where CoQ10 and other quinones have been tested. CoQ10 is presently being used in a large phase III trial in Parkinson's disease. CoQ10 has been found to improve sperm count and motility on asthenozoospermia. Moreover, for the first time CoQ10 was found to decrease the incidence of preeclampsia in pregnancy. The ability of CoQ10 to mitigate headache symptoms in adults was also verified in pediatric and adolescent populations.
Probiotics are live microorganisms that confer several beneficial effects to the host, including enhancement of bone mineralization. However, probiotic action on bone regeneration is not well studied ...and therefore we analysed various effects of probiotic treatment on the caudal fin regeneration of zebrafish. Morphological analysis revealed an increased regenerated area with shorter and thicker lepidotrichia segments after probiotic treatment. Fourier transform infrared spectroscopy imaging analysis highlighted the distribution of phosphate groups in the regenerated fins and probiotic group showed higher amounts of well-crystallized hydroxyapatite. At the midpoint (5 days post amputation) of regeneration, probiotics were able to modulate various stages of osteoblast differentiation as confirmed by the upregulation of some key marker genes such as runx2b, sp7, col10a1a, spp1 and bglap, besides suppressing osteoclast activity as evidenced from the downregulation of ctsk. Probiotics also caused an enhanced cell cycle by regulating the expression of genes involved in Retinoic acid (rarga, cyp26b1) and Wnt/β-catenin (ctnnb1, ccnd1, axin2, sost) signaling pathways, and also modulated phosphate homeostasis by increasing the entpd5a levels. These findings provide new outlooks for the use of probiotics as a prophylactic treatment in accelerating bone regeneration and improving skeletal health in both aquaculture and biomedical fields.
For a number of years, coenzyme Q (CoQ10 in humans) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in plasma, ...and extensively investigated its antioxidant role. These two functions constitute the basis on which research supporting the clinical use of CoQ10 is founded. Also at the inner mitochondrial membrane level, coenzyme Q is recognized as an obligatory co-factor for the function of uncoupling proteins and a modulator of the transition pore. Furthermore, recent data reveal that CoQ10 affects expression of genes involved in human cell signalling, metabolism, and transport and some of the effects of exogenously administered CoQ10 may be due to this property. Coenzyme Q is the only lipid soluble antioxidant synthesized endogenously. In its reduced form, CoQH2, ubiquinol, inhibits protein and DNA oxidation but it is the effect on lipid peroxidation that has been most deeply studied. Ubiquinol inhibits the peroxidation of cell membrane lipids and also that of lipoprotein lipids present in the circulation. Dietary supplementation with CoQ10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoproteins to the initiation of lipid peroxidation. Moreover, CoQ10 has a direct anti-atherogenic effect, which has been demonstrated in apolipoprotein E-deficient mice fed with a high-fat diet. In this model, supplementation with CoQ10 at pharmacological doses was capable of decreasing the absolute concentration of lipid hydroperoxides in atherosclerotic lesions and of minimizing the size of atherosclerotic lesions in the whole aorta. Whether these protective effects are only due to the antioxidant properties of coenzyme Q remains to be established; recent data point out that CoQ10 could have a direct effect on endothelial function. In patients with stable moderate CHF, oral CoQ10 supplementation was shown to ameliorate cardiac contractility and endothelial dysfunction. Recent data from our laboratory showed a strong correlation between endothelium bound extra cellular SOD (ecSOD) and flow-dependent endothelial-mediated dilation, a functional parameter commonly used as a biomarker of vascular function. The study also highlighted that supplementation with CoQ10 that significantly affects endothelium-bound ecSOD activity. Furthermore, we showed a significant correlation between increase in endothelial bound ecSOD activity and improvement in FMD after CoQ10 supplementation. The effect was more pronounced in patients with low basal values of ecSOD. Finally, we summarize the findings, also from our laboratory, on the implications of CoQ10 in seminal fluid integrity and sperm cell motility.
The present study explored what effect manufacturing has on the antioxidant properties of teas coming from a single cultivar but processed differently to give a white, two black (Orthodox and CTC) ...and two green (low-caffeine and non-decaffeinated) teas. Total phenol (TPC), flavonoids (TFC), theaflavins, individual catechins content, and chelating activity were also investigated. Using the ABTS, ORAC and LDL assays the following ‘antioxidant profile’ was obtained: green≥low-caffeine green>white≥black Orthodox>black CTC, with statistically significant correlation between ORAC and LDL assays (r2=0.444, p=0.0067), whereas TPC and TFC significantly correlate with the ABTS one (r2=0.871, p=0.000 and r2=0.438, p=0.007, respectively). Metal chelating activity, which was lowest in the green teas, does not correlate with antioxidant activity but appears to be influenced by theaflavins content. The results contribute to better understand how the manufacturing process influences the antioxidant activity of tea when variables (geographical region, environmental conditions, cultivar type, plucking techniques) are kept to a minimum. Secondly, we show that novel African green, white and black Orthodox teas, made from tea varieties typically used in black CTC tea production, may have potential health benefits comparable with commonly consumed teas.
► Antioxidant activity (AA) of tea from same cultivar but processed differently. ► When tea processing is the only variable, AA is highest in green tea. ► AA correlates with total phenol, flavonoid and catechins content. ► Metal-chelating activity correlates with total theaflavin content. ► Novel African green, white and black orthodox teas have potential health benefits.
Metabolic complications in an obese state can be aggravated by an abnormal inflammatory response and enhanced production of reactive oxygen species. Pro-inflammatory response is known to be ...associated with the formation of toxic reactive oxygen species and subsequent generation of oxidative stress. Indeed, adipocytes from obese individuals display an altered adipokine profile, with upregulated expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL-6). Interestingly, natural compounds, including phenolic enriched foods are increasingly explored for their ameliorative effects against various metabolic diseases. Of interest is gallic acid, a trihydroxybenzoic acid that has progressively demonstrated robust anti-obesity capabilities in various experimental models. In addition to reducing excessive lipid storage in obese subjects, gallic acid has been shown to specifically target the adipose tissue to suppress lipogenesis, improve insulin signaling, and concomitantly combat raised pro-inflammatory response and oxidative stress. This review will revise mechanisms involved in the pathophysiological effects of inflammation and oxidative stress in an obese state. To better inform on its therapeutic potential and improvement of human health, available evidence reporting on the anti-obesity properties of gallic acid and its derivatives will be discussed, with emphases on its modulatory effect on molecular mechanisms involved in insulin signaling, inflammation and oxidative stress.
Many neurodegenerative and inherited metabolic diseases frequently compromise nervous system function, and mitochondrial dysfunction and oxidative stress have been implicated as key events leading to ...neurodegeneration. Mitochondria are essential for neuronal function; however, these organelles are major sources of endogenous reactive oxygen species and are vulnerable targets for oxidative stress-induced damage. The brain is very susceptible to oxidative damage due to its high metabolic demand and low antioxidant defence systems, therefore minimal imbalances in the redox state can result in an oxidative environment that favours tissue damage and activates neuroinflammatory processes. Mitochondrial-associated molecular pathways are often compromised in the pathophysiology of neurodegeneration, including the parkin/PINK1, Nrf2, PGC1α, and PPARγ pathways. Impairments to these signalling pathways consequently effect the removal of dysfunctional mitochondria, which has been suggested as contributing to the development of neurodegeneration. Mitochondrial dysfunction prevention has become an attractive therapeutic target, and there are several molecular pathways that can be pharmacologically targeted to remove damaged mitochondria by inducing mitochondrial biogenesis or mitophagy, as well as increasing the antioxidant capacity of the brain, in order to alleviate mitochondrial dysfunction and prevent the development and progression of neurodegeneration in these disorders. Compounds such as natural polyphenolic compounds, bioactive quinones, and Nrf2 activators have been reported in the literature as novel therapeutic candidates capable of targeting defective mitochondrial pathways in order to improve mitochondrial function and reduce the severity of neurodegeneration in these disorders.
Retinitis pigmentosa (RP) is a group of mitochondrial diseases characterized by progressive degeneration of rods and cones leading to retinal loss of light sensitivity and, consequently, to ...blindness. To date, no cure is available according to the clinical literature. As a disease associated with pigmentation-related, pro-oxidant state, and mitochondrial dysfunction, RP may be viewed at the crossroads of different pathogenetic pathways involved in adverse health outcomes, where mitochondria play a preeminent role. RP has been investigated in a number of experimental and clinical studies aimed at delaying retinal hyperpigmentation by means of a number of natural and synthetic antioxidants, as well as mitochondrial cofactors, also termed mitochondrial nutrients (MNs), such as alpha-lipoic acid, coenzyme Q10 and carnitine. One should consider that each MN plays distinct—and indispensable—roles in mitochondrial function. Thus, a logical choice would imply the administration of MN combinations, instead of individual MNs, as performed in previous studies, and with limited, if any, positive outcomes. A rational study design aimed at comparing the protective effects of MNs, separately or in combinations, and in association with other antioxidants, might foresee the utilization of animal RP models. The results should verify a comparative optimization in preventing or effectively contrasting retinal oxidative stress in mouse RP models and, in prospect, in human RP cases.
Background
The mitochondrial cofactors
α
-lipoic acid (ALA), coenzyme Q10 (CoQ10) and carnitine (CARN) play distinct and complementary roles in mitochondrial functioning, along with strong ...antioxidant actions. Also termed mitochondrial nutrients (MNs), these cofactors have demonstrated specific protective actions in a number of chronic disorders, as assessed in a well-established body of literature.
Methods
Using PubMed, the authors searched for articles containing information on the utilization of MNs in inflammatory disorders as assessed from in vitro and animal studies, and in clinical trials, in terms of exerting anti-inflammatory actions.
Results
The retrieved literature provided evidence relating acute pathologic conditions, such as sepsis and pneumonia, with a number of redox endpoints of biological and clinical relevance. Among these findings, both ALA and CARN were effective in counteracting inflammation-associated redox biomarkers, while CoQ10 showed decreased levels in proinflammatory conditions. MN-associated antioxidant actions were applied in a number of acute disorders, mostly using one MN. The body of literature assessing the safety and the complementary roles of MNs taken together suggests an adjuvant role of MN combinations in counteracting oxidative stress in sepsis and other acute disorders, including COVID-19-associated pneumonia.
Conclusions
The present state of art in the use of individual MNs in acute disorders suggests planning adjuvant therapy trials utilizing MN combinations aimed at counteracting proinflammatory conditions, as in the case of pneumonia and the COVID-19 pandemic.
Three killer toxins that were previously investigated, one excreted by Kluyveromyces wickerhamii and two by different strains of Wickerhamomyces anomalus, were produced at the pilot scale, ...lyophilized and characterized, and the formulates were assessed for their zymocidial effect against Brettanomyces bruxellensis spoilage yeast. A comparative analysis allowed the evaluation of the minimum inhibitory concentration (MIC) against a sensitive strain. Fungicidal and fungistatic concentrations were used to evaluate the cytocidal effect using a cytofluorimetric approach that confirmed the lethal effect of all lyophilized formulates against
spoilage yeasts. Moreover, the potential killer toxins' cytotoxicity against human intestinal cells (Caco-2) were evaluated to exclude any possible negative effect on the consumers. Finally, the effective lethal effect of all three lyophilized killer toxins toward
sensitive strain were tested. The results indicated that all of them acted without dangerous effects on the human epithelial cells, opening the way for their possible commercial application. In particular, D15 showed the lowest MIC and the highest activity, was evaluated also in wine, revealing a strong reduction of
yeast growth and, at the same time, a control of ethyl phenols production.
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder currently affecting the ageing population. Although the aetiology of PD has yet to be fully elucidated, environmental ...factors such as exposure to the naturally occurring neurotoxin rotenone has been associated with an increased risk of developing PD. Rotenone inhibits mitochondrial respiratory chain (MRC) complex I activity as well as induces dopaminergic neuronal death. The aim of the present study was to investigate the underlying mechanisms of rotenone-induced mitochondrial dysfunction and oxidative stress in an in vitro SH-SY5Y neuronal cell model of PD and to assess the ability of pre-treatment with Coenzyme Q10 (CoQ10) to ameliorate oxidative stress in this model. Spectrophotometric determination of the mitochondrial enzyme activities and fluorescence probe studies of reactive oxygen species (ROS) production was assessed. Significant inhibition of MRC complex I and II–III activities was observed, together with a significant loss of neuronal viability, CoQ10 status, and ATP synthesis. Additionally, significant increases were observed in intracellular and mitochondrial ROS production. Remarkably, CoQ10 supplementation was found to reduce ROS formation. These results have indicated mitochondrial dysfunction and increased oxidative stress in a rotenone-induced neuronal cell model of PD that was ameliorated by CoQ10 supplementation.
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