Coenzyme Q10-Loaded Albumin Nanoparticles Protect against Redox Imbalance and Inflammatory, Apoptotic, and Histopathological Alterations in Mercuric Chloride-Induced Hepatorenal Toxicity in Rats
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SUBMITTER: Ramadan S
PROVIDER: S-EPMC10669886 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:For a number of years, coenzyme Q10 (CoQ10) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in blood plasma, and extensively investigated its antioxidant role. These 2 functions constitute the basis for supporting the clinical use of CoQ10. Also, at the inner mitochondrial membrane level, CoQ10 is recognized as an obligatory cofactor for the function of uncoupling proteins and a modulator of the mitochondrial transition pore. Furthermore, recent data indicate that CoQ10 affects the expression of genes involved in human cell signaling, metabolism and transport, and some of the effects of CoQ10 supplementation may be due to this property. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, aging-related oxidative stress and carcinogenesis processes, and also statin treatment. Many neurodegenerative disorders, diabetes, cancer, and muscular and cardiovascular diseases have been associated with low CoQ10 levels as well as different ataxias and encephalomyopathies. CoQ10 treatment does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Oral administration of CoQ10 is a frequent antioxidant strategy in many diseases that may provide a significant symptomatic benefit.
| S-EPMC4112525 | biostudies-literature
Project description:Ubiquinone (coenzyme Q(10) or CoQ(10)) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions. Deficiency of CoQ(10) (MIM 607426) has been associated with five different clinical presentations that suggest genetic heterogeneity, which may be related to the multiple steps in CoQ(10) biosynthesis. Patients with all forms of CoQ(10) deficiency have shown clinical improvements after initiating oral CoQ(10) supplementation. Thus, early diagnosis is of critical importance in the management of these patients. This year, the first molecular defect causing the infantile form of primary human CoQ(10) deficiency has been reported. The availability of genetic testing will allow for a better understanding of the pathogenesis of this disease and early initiation of therapy (even presymptomatically in siblings of patients) in this otherwise life-threatening infantile encephalomyopathy.
| S-EPMC1832150 | biostudies-literature
Project description:BackgroundCoenzyme Q10 (CoQ10) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ10 deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ10 status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3G272S , CoQ6M406V, CoQ7M103T), reduction (NQO1P187S, NQO2L47F) and metabolism (apoE3/4) of CoQ10 and their association with CoQ10 status. For this purpose, CoQ10 serum levels of 54 healthy male volunteers were determined before (T0) and after a 14 days supplementation (T14) with 150 mg/d of the reduced form of CoQ10.FindingsAt T0, the CoQ10 level of heterozygous NQO1P187S carriers were significantly lower than homozygous S/S carriers (0.93 ± 0.25 μM versus 1.34 ± 0.42 μM, p = 0.044). For this polymorphism a structure homology-based method (PolyPhen) revealed a possibly damaging effect on NQO1 protein activity. Furthermore, CoQ10 plasma levels were significantly increased in apoE4/E4 genotype after supplementation in comparison to apoE2/E3 genotype (5.93 ± 0.151 μM versus 4.38 ± 0.792 μM, p = 0.034). Likewise heterozygous CoQ3G272S carriers had higher CoQ10 plasma levels at T14 compared to G/G carriers but this difference did not reach significance (5.30 ± 0.96 μM versus 4.42 ± 1.67 μM, p = 0.082).ConclusionsIn conclusion, our pilot study provides evidence that NQO1P187S and apoE polymorphisms influence CoQ10 status in humans.
| S-EPMC3160390 | biostudies-literature
Project description:ObjectivesThe goal of this investigation was to determine if acute influenza infection is associated with depletion of CoQ10 compared to healthy controls and to determine any associations between CoQ10 levels and illness severity and inflammatory biomarkers.Patients and methodsWe analyzed serum CoQ10 concentrations of patients with acute influenza enrolled in a randomized clinical trial prior to study drug administration. Patients were enrolled at a single urban tertiary care center over 3 influenza seasons (December 27, 2013 to March 31, 2016). Wilcoxon rank sum test was used to compare CoQ10 levels between influenza patients and healthy controls. Correlations with inflammatory biomarkers and severity of illness were assessed using Spearman correlation coefficient.ResultsWe analyzed CoQ10 levels from 50 patients with influenza and 29 controls. Overall, patients with acute influenza had lower levels of CoQ10 (.53 μg/mL, IQR .37-.75 vs .72, IQR .58-.90, P = .004). Significantly more patients in the influenza group had low CoQ10 levels (<.5 μg/mL) compared to controls (48% vs 7%, P < .001). Among influenza patients, there were significant but weak correlations between CoQ10 levels and IL-2 (r = -.30, P = .04), TNF-alpha (r = -.35, P = .01) and VEGF (r = .38, P = .007), but no correlation with IL-6, IL-10, VCAM or influenza severity of illness score (all P > .05).ConclusionsWe found that CoQ10 levels were significantly lower in patients with acute influenza infection and that these levels had significant although weak correlations with several inflammatory biomarkers.
| S-EPMC6304320 | biostudies-literature
Project description: Not available
| S-EPMC8092430 | biostudies-literature
Project description:Highlights • PM produced oxidative stress in gastric, liver, and kidney tissue.• PM-induced toxicity was mediated by ROS and mitochondrial dysfunction.• PM enhanced the activated caspase-3 expression.• CoQ10 alleviates PM-induced gastropathy and hepato-renal damage.• CoQ10 might be effective in COVID-19 treatment regimen. Piroxicam (PM) is an oxicam-NSAID commonly recommended for various pain and associated inflammatory disorders. However, it is reported to have a gastric and hepato-renal toxic effect. Therefore, the current research was planned to investigate the possible mechanisms behind the mitigating action of the coenzyme (CoQ10), a natural, free radical scavenger, against PM tissue injury. Rats were assigned to five equal groups; Control, CoQ10 (10 mg/kg, orally), PM (7 mg/kg, i.p.), CoQ + PM L, and CoQ + PM H group. After 28 days, PM provoked severe gastric ulceration and marked liver and kidney damage indicated by an elevated gastric ulcer index and considerable alteration in liver and kidney biochemical tests. The toxic effects might be attributed to mitochondrial dysfunction and excess generation of reactive oxygen species (ROS), as indicated by enhanced malondialdehyde (MDA) levels along with decreased reduced-glutathione (GSH) levels and catalase (CAT) activity. Apoptotic cell death also was demonstrated by increased regulation of activated caspase-3 in the stomach, liver, and kidney tissues. Interestingly, external supplementation of CoQ10 attenuated the PM-inflicted deleterious oxidative harm and apoptosis. This ameliorative action was ascribed to the free radical scavenging activity of CoQ10.
| S-EPMC7453214 | biostudies-literature
Project description:The human syndrome of coenzyme Q (CoQ) deficiency is a heterogeneous mitochondrial disease characterized by a diminution of CoQ content in cells and tissues that affects all the electron transport processes CoQ is responsible for, like the electron transference in mitochondria for respiration and ATP production and the antioxidant capacity that it exerts in membranes and lipoproteins. Supplementation with external CoQ is the main attempt to address these pathologies, but quite variable results have been obtained ranging from little response to a dramatic recovery. Here, we present the importance of modeling human CoQ deficiencies in animal models to understand the genetics and the pathology of this disease, although the election of an organism is crucial and can sometimes be controversial. Bacteria and yeast harboring mutations that lead to CoQ deficiency are unable to grow if they have to respire but develop without any problems on media with fermentable carbon sources. The complete lack of CoQ in mammals causes embryonic lethality, whereas other mutations produce tissue-specific diseases as in humans. However, working with transgenic mammals is time and cost intensive, with no assurance of obtaining results. Caenorhabditis elegans and Drosophila melanogaster have been used for years as organisms to study embryonic development, biogenesis, degenerative pathologies, and aging because of the genetic facilities and the speed of working with these animal models. In this review, we summarize several attempts to model reliable human CoQ deficiencies in invertebrates, focusing on mutant phenotypes pretty similar to those observed in human patients.
| S-EPMC4112529 | biostudies-literature
Project description:Coenzyme Q10 (CoQ10) is an essential cofactor in the mitochondrial respiratory chain, and as a dietary supplement it has recently gained attention for its potential role in the treatment of neurodegenerative disease. Evidence for mitochondrial dysfunction in neurodegenerative disorders derives from animal models, studies of mitochondria from patients, identification of genetic defects in patients with neurodegenerative disease, and measurements of markers of oxidative stress. Studies of in vitro models of neuronal toxicity and animal models of neurodegenerative disorders have demonstrated potential neuroprotective effects of CoQ10. With this data in mind, several clinical trials of CoQ10 have been performed in Parkinson's disease and atypical Parkinson's syndromes, Huntington's disease, Alzheimer disease, Friedreich's ataxia, and amyotrophic lateral sclerosis, with equivocal findings. CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy. Phase III trials of high-dose CoQ10 in large sample sizes are needed to further ascertain the effects of CoQ10 in neurodegenerative diseases.
| S-EPMC2785862 | biostudies-literature
Project description:Coenzyme Q (CoQ) is an essential component of the respiratory chain but also participates in other mitochondrial functions such as regulation of the transition pore and uncoupling proteins. Furthermore, this compound is a specific substrate for enzymes of the fatty acids beta-oxidation pathway and pyrimidine nucleotide biosynthesis. Furthermore, CoQ is an antioxidant that acts in all cellular membranes and lipoproteins. A complex of at least ten nuclear (COQ) genes encoded proteins synthesizes CoQ but its regulation is unknown. Since 1989, a growing number of patients with multisystemic mitochondrial disorders and neuromuscular disorders showing deficiencies of CoQ have been identified. CoQ deficiency caused by mutation(s) in any of the COQ genes is designated primary deficiency. Other patients have displayed other genetic defects independent on the CoQ biosynthesis pathway, and are considered to have secondary deficiencies. This review updates the clinical and molecular aspects of both types of CoQ deficiencies and proposes new approaches to understanding their molecular bases.
| S-EPMC3245903 | biostudies-literature
Project description:Our present study reveals significant decelerating effects on senescence processes in middle-aged SAMP1 mice supplemented for 6 or 14 months with the reduced form (QH2, 500 mg/ kg BW/ day) of coenzyme Q10 (CoQ10). To unravel molecular mechanisms of these CoQ10 effects, a genome-wide transcript profiling in liver, heart, brain and kidney of SAMP1 mice supplemented with the reduced (QH2) or oxidized form of CoQ10 (Q10) was performed. Liver seems to be the main target tissue of CoQ10 intervention, followed by kidney, heart and brain. Stringent evaluation of the resulting data revealed that QH2 has a stronger impact on gene expression than Q10, which was primarily due to differences in the bioavailability. Indeed, we found that QH2 supplementation was more effective than Q10 to increase levels of CoQ10 in the liver of SAMP1 mice (54.92-fold and 30.36-fold, respectively). To identify functional and regulatory connections of the “top 50” (p < 0.05) up- and down-regulated QH2-sensitive transcripts in liver (fold changes ranging from 21.24 to -6.12), text mining analysis (Genomatix BiblioSphere, GFG level B3) was used. Hereby, we identified 11 QH2-sensitive genes which are regulated by PPAR-α and are primarily involved in cholesterol synthesis (e.g. HMGCS1, HMGCL, HMGCR), fat assimilation (FABP5), lipoprotein metabolism (PLTP) and inflammation (STAT-1). Thus, we provide evidence that QH2 is involved in the reduction of fat and cholesterol synthesis via modulation of the PPAR-α signalling pathway. These data may explain, at least in part, the observed effects on decelerated age-dependent degeneration processes in QH2-supplemented SAMP1 mice.
2010-03-05 | GSE15129 | GEO