Coenzyme Q10 Ameliorates Ultraviolet B Irradiation Induced Cell Death Through Inhibition of Mitochondrial Intrinsic Cell Death Pathway

Ultraviolet B (UVB) induces cell death by increasing free radical production, activating apoptotic cell death pathways and depolarizing mitochondrial membrane potential. Coenzyme Q10 (CoQ10), an essential cofactor in the mitochondrial electron transport chain, serves as a potent antioxidant in the mitochondria. The aim of the present study is to establish whether CoQ10 is capable of protecting neuronal cells against UVB-induced damage. Murine hippocampal HT22 cells were treated with 0.01, 0.1 or 1 μM of CoQ10 3 or 24 h prior to the cells being exposed to UVB irradiation. The CoQ10 concentrations were maintained during irradiation and 24 h post-UVB. Cell viability was assessed by counting viable cells and MTT conversion assay. Superoxide production and mitochondrial membrane potential were measured using fluorescent probes. Levels of cleaved caspase-9, caspase-3, and apoptosis-inducing factor (AIF) were detected using immunocytochemistry and Western blotting. The results showed that UVB irradiation decreased cell viability and such damaging effect was associated with increased superoxide production, mitochondrial depolarization, and activation of caspase-9 and caspase-3. Treatment with CoQ10 at three different concentrations started 24 h before UVB exposure significantly increased the cell viability. The protective effect of CoQ10 was associated with reduction in superoxide production, normalization of mitochondrial membrane potential and inhibition of caspase-9 and caspase-3 activation. It is concluded that the neuroprotective effect of CoQ10 results from inhibiting oxidative stress and blocking caspase-3 dependent cell death pathway

Exogenous coenzyme Q10 modulates MMP-2 activity in MCF-7 cell line as a breast cancer cellular model

<p>Abstract</p> <p>Background/Aims</p> <p>Matrix Metalloproteinases 2 is a key molecule in cellular invasion and metastasis. Mitochondrial ROS has been established as a mediator of MMP activity. Coenzyme Q₁₀contributes to intracellular ROS regulation. Coenzyme Q₁₀beneficial effects on cancer are still in controversy but there are indications of Coenzyme Q₁₀complementing effect on tamoxifen receiving breast cancer patients.</p> <p>Methods</p> <p>In this study we aimed to investigate the correlation of the effects of co-incubation of coenzyme Q10 and N-acetyl-L-cysteine (NAC) on intracellular H2O2 content and Matrix Metalloproteinase 2 (MMP-2) activity in MCF-7 cell line.</p> <p>Results and Discussion</p> <p>Our experiment was designed to assess the effect in a time and dose related manner. Gelatin zymography and Flowcytometric measurement of H2O2 by 2'7',-dichlorofluorescin-diacetate probe were employed. The results showed that both coenzyme Q10 and N-acetyl-L-cysteine reduce MMP-2 activity along with the pro-oxidant capacity of the MCF-7 cell in a dose proportionate manner.</p> <p>Conclusions</p> <p>Collectively, the present study highlights the significance of Coenzyme Q₁₀effect on the cell invasion/metastasis effecter molecules.</p

Effect of Coenzyme Q10 on ischemia and neuronal damage in an experimental traumatic brain-injury model in rats

<p>Abstract</p> <p>Background</p> <p>Head trauma is one of the most important clinical issues that not only can be fatal and disabling, requiring long-term treatment and care, but also can cause heavy financial burden. Formation or distribution of free oxygen radicals should be decreased to enable fixing of poor neurological outcomes and to prevent neuronal damage secondary to ischemia after trauma. Coenzyme Q₁₀(CoQ₁₀), a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. In this study, the role of CoQ₁₀in the treatment of head trauma is researched by analyzing the histopathological and biochemical effects of CoQ₁₀administered after experimental traumatic brain injury in rats. A traumatic brain-injury model was created in all rats. Trauma was inflicted on rats by the free fall of an object of 450 g weight from a height of 70 cm on the frontoparietal midline onto a metal disc fixed between the coronal and the lambdoid sutures after a midline incision was carried out.</p> <p>Results</p> <p>In the biochemical tests, tissue malondialdehyde (MDA) levels were significantly higher in the traumatic brain-injury group compared to the sham group (<it>p </it>< 0.05). Administration of CoQ₁₀after trauma was shown to be protective because it significantly lowered the increased MDA levels (<it>p </it>< 0.05). Comparing the superoxide dismutase (SOD) levels of the four groups, trauma + CoQ₁₀group had SOD levels ranging between those of sham group and traumatic brain-injury group, and no statistically significant increase was detected. Histopathological results showed a statistically significant difference between the CoQ₁₀and the other trauma-subjected groups with reference to vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia, and axonal edema (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ₁₀use in rats with traumatic brain injury.</p

Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia: Coenzyme Q10 Effect on Clinical Improvement

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q 10 (CoQ 10) supplementation on biochemical markers and clinical improvement were also evaluated. [Methods]: We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ 10, catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. [Results]: We found decreased CoQ 10, catalase and ATP levels in BMCs from FM patients as compared to normal control (P<0.05 and P<0.001, respectively) We also found increased level of LPO in BMCs from FM patients as compared to normal control (P<0.001). Significant negative correlations between CoQ 10 or catalase levels in BMCs and headache parameters were observed (r = -0.59, P<0.05; r = -0.68, P<0.05, respectively). Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<.05). Oral CoQ 10 supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P<0.001). [Discussion]: The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM.This work has been supported by IV Plan Propio de Investigación (University of Seville, ref. 2010/00000453), FIS PI10/00543 grant, FIS EC08/00076 grant, Ministerio de Sanidad, Spain and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), SAS 111242 grant, Servicio Andaluz de Salud-Junta de Andalucía, Proyecto de Investigación de Excelencia de la Junta de Andalucía CTS-5725 and Federación Andaluza de Fibromialgia y Fatiga Crónica (ALBA Andalucía).Peer Reviewe

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health

The poly-omics of ageing through individual-based metabolic modelling

Abstract Background Ageing can be classified in two different ways, chronological ageing and biological ageing. While chronological age is a measure of the time that has passed since birth, biological (also known as transcriptomic) ageing is defined by how time and the environment affect an individual in comparison to other individuals of the same chronological age. Recent research studies have shown that transcriptomic age is associated with certain genes, and that each of those genes has an effect size. Using these effect sizes we can calculate the transcriptomic age of an individual from their age-associated gene expression levels. The limitation of this approach is that it does not consider how these changes in gene expression affect the metabolism of individuals and hence their observable cellular phenotype. Results We propose a method based on poly-omic constraint-based models and machine learning in order to further the understanding of transcriptomic ageing. We use normalised CD4 T-cell gene expression data from peripheral blood mononuclear cells in 499 healthy individuals to create individual metabolic models. These models are then combined with a transcriptomic age predictor and chronological age to provide new insights into the differences between transcriptomic and chronological ageing. As a result, we propose a novel metabolic age predictor. Conclusions We show that our poly-omic predictors provide a more detailed analysis of transcriptomic ageing compared to gene-based approaches, and represent a basis for furthering our knowledge of the ageing mechanisms in human cells

Beneficial Effects of a Q-ter® Based Nutritional Mixture on Functional Performance, Mitochondrial Function, and Oxidative Stress in Rats

Mitochondrial dysfunction and oxidative stress are central mechanisms underlying the aging process and the pathogenesis of many age-related diseases. Selected antioxidants and specific combinations of nutritional compounds could target many biochemical pathways that affect both oxidative stress and mitochondrial function and, thereby, preserve or enhance physical performance. supplementation in rats at 29 months of age. supplementation may be particularly beneficial when initiated prior to major biological and functional declines that appear to occur with advancing age

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome