Coenzyme Q10 Supplementation Research Articles

Evaluation of efficacy and safety of coenzyme Q10 in pediatric hemodialysis patients: a randomized controlled trial

BackgroundThere is evidence from clinical trials that coenzyme Q10 significantly improves mitochondrial function and decreases oxidative stress and cardiovascular disease in adult hemodialysis patients. However, we have never fully investigated its role in pediatric patients before. This study aimed to assess the effects of coenzyme Q10 supplementation on oxidative stress and inflammatory markers in pediatric hemodialysis patients. This was a prospective, randomized, double-blinded, placebo-controlled trial. Thirty-six pediatric hemodialysis patients were recruited and simply randomized to receive either oral coenzyme Q10 (3–5 mg/kg) daily or placebo daily for 12 weeks.ResultsUsing the Mann–Whitney test, children in the intervention group showed a significant reduction in the median percent change of blood urea nitrogen from baseline of − 58.18 versus − 9.6 in the placebo group (p = 0.002). The median percent change of serum malondialdehyde significantly decreased by − 55.68 in the intervention group, while it increased by 39.75 in the placebo group (p < 0.001). Additionally, the median percent change from baseline in serum tumor necrosis factor-α levels significantly decreased by − 46.69 in the intervention group and increased by 8.5 in the placebo group (p = 0.03).ConclusionSupplementation of oral coenzyme Q10 may have beneficial effects on oxidative stress and inflammatory markers in pediatric hemodialysis patients. This study emphasized the potential efficacy of an average coenzyme Q10 dose of 4 mg/kg/day in pediatric hemodialysis patients; this gives the green light for other researchers to confidently evaluate larger doses as an attempt to control the systemic inflammation in this patient population. Further research is needed to determine whether coenzyme Q10 treatment improves clinical outcomes such as infection, hospitalization, cardiovascular events, and mortality in pediatric hemodialysis patients.Trial Registration Clinical trials.gov, NCT05170893, Registered 28 December 2021, https://clinicaltrials.gov/study/NCT05170893?cond=NCT05170893&rank=1.Graphical abstract

Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review.

Primary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood. The disease often progresses to kidney failure and the renal histopathology is most commonly focal segmental glomerulosclerosis (FSGS). Four SRNS cases (2 females and 2 males) from 2 unrelated families who were followed clinically for nearly 3 years. Clinical exome testing and analyses were performed by MyGenostics Laboratory in China to evaluate unexplained proteinuria given the strong family history of glomerular disease and histologic evidence of SRNS. Pathogenic variants were identified in COQ8B in the exome studies and confirmed by direct sequencing. Clinical exome sequencing revealed biallelic variants of the COQ8B gene in 2 families. In the Family 1, the oldest of three affected siblings died of renal failure at 11 years of age. Based on the results of genetic testing which identified a homozygous variant of COQ8B, the other two affected siblings with mild proteinuria and normal renal function were treated with CoQ10 oral supplementation at an early stage. Coenzyme Q10 treatment was effective in reducing proteinuria levels in both patients from Family 1 over the first 6 months and the two patients still have low-level proteinuria and normal renal function at nearly three years. In Family 2, clinical exome sequencing revealed a compoundheterozygous variants of COQ8B in a patient with biopsy- proven FSGS. His disease was unresponsive to prior treatment with glucocorticoids and cyclosporine. Oral CoQ10 was initiated based on his genetic diagnosis and was it was effective in reducing proteinuria over the first 5 months months of therapy. However after 1 year, his disease progressed tokidney failure. Kidney transplantation was performed at 5 years of age and his condition has been stable without rejection and no recurrence of disease. COQ8B gene variant-related glomerulopathy often presents as SRNS without obvious extrarenal manifestations. The histopathology is mainly FSGS and follows an autosomal recessive mode of inheritance. Some patients may benefit from early coenzyme Q10 supplementation. For patients whose disease progresses to kidney failure, kidney transplantation can be an effective treatment. For children with unexplained proteinuria and abnormal renal function, genetic testing should be performed early in the course of disease to guide therapy where possible and improve prognosis.

Coenzyme Q and Selenium Co-Supplementation Alleviate Methionine Choline-Deficient Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice.

The pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) is closely associated with increased oxidative stress and lipid peroxidation. Coenzyme Q (CoQ) and selenium (Se) are well-established antioxidants with protective effects against oxidative damage. This study aimed to investigate the effects of CoQ and Se in ameliorating MASH induced by a methionine choline-deficient (MCD) diet in mice. C57BL/6J male mice were fed either a methionine choline-sufficient (MCS) or MCD diet and treated with vehicle, CoQ (100 mg/kg), Se (158 μg/kg), or their combination (CoQ + Se) for 4 weeks. The MCD diet significantly increased hepatic steatosis, inflammation, and fibrosis compared to MCS controls. Treatment with CoQ and Se, particularly in combination, markedly reduced the MAFLD activity score, hepatic inflammation, and fibrosis. Combined supplementation of CoQ and Se significantly decreased serum alanine aminotransferase and aspartate aminotransferase levels and hepatic TG and cholesterol concentrations. CoQ and Se effectively mitigated hepatic oxidative stress by enhancing catalase and superoxide dismutase activities, increasing glutathione peroxidase (GPX) activity, and restoring the GSH/GSSG ratio. Lipid peroxidation markers, such as malondialdehyde and 4-hydroxynonenal, were significantly reduced. Furthermore, the expression of ferroptosis-related markers, including acyl-CoA synthetase long-chain family member 4, arachidonate 12-lipoxygenase, and hepatic non-heme iron content, was significantly downregulated, while GPX4 expression was upregulated by combined CoQ and Se treatment. CoQ and Se synergistically alleviate MASH progression by reducing oxidative stress and lipid peroxidation, which may contribute to the suppression of ferroptosis. Combined CoQ and Se supplementation demonstrates therapeutic potential for managing MASH and related liver injury.

The Role of Coenzyme Q10 in Modern Medicine: Insights into Energy Metabolism and Antioxidant Therapy

Background: Coenzyme Q10 (CoQ10), a key component of mitochondrial energy production and a potent antioxidant, plays an essential role in addressing oxidative stress and mitochondrial dysfunction. Its applications span cardiovascular health, infectious diseases, neurological conditions, reproductive health, and fatigue management. However, gaps remain in understanding its optimal dosing, long-term impact, and efficacy across diverse health conditions. Methods: This review synthesized findings from clinical trials, meta-analyses, and observational studies. A systematic search of PubMed and ScienceDirect was conducted, selecting studies based on methodological rigor and relevance to CoQ10’s mechanisms, efficacy, and safety. Results: CoQ10 supplementation reduced cardiovascular mortality, alleviated migraine symptoms, improved mitochondrial function, and decreased oxidative stress. Promising but inconclusive evidence supports its role in managing statin-induced myopathy and enhancing reproductive outcomes. CoQ10 was consistently shown to be safe and well-tolerated. Conclusion: CoQ10 demonstrates significant therapeutic potential across several health conditions. Its antioxidant and bioenergetic benefits are well-documented, but further research is needed to refine dosing strategies and evaluate long-term effects. CoQ10 remains a promising complementary therapy for modern health challenges.

Does coenzyme Q10 improve semen quality and circulating testosterone level? a systematic review and meta-analysis of randomized controlled trials.

Seminal oxidative stress has been shown to be a key factor in the development of male infertility. However, the benefits of infertility treatments with antioxidants such as coenzyme Q10 (CoQ10) remains controversial. The aim of the present study was to assess the effects of CoQ10 supplementation on semen quality, i.e., semen volume, total sperm number, sperm concentration, total sperm motility, percentage of progressive sperm motility and sperm morphology. In addition, the effects of CoQ10 supplementation on circulating testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin B levels were evaluated. A systematic review and a meta-analysis of randomized controlled trials (RCTs) were performed to assess the effects of CoQ10 supplementation on semen quality and serum levels of male reproductive hormones. We conducted a strategic literature search in the Cochrane, EMBASE, PubMed/MEDLINE, Scopus, and Web of Science databases and collected only RCTs. The data in the collected RCTs were then meta-analyzed according to PRISMA guidelines. Out of 2,144 collected studies, only eight were classified eligible. The studies included a total of 877 male subjects; 462 CoQ10-treated and 415 untreated/placebo-treated. We found significantly higher total sperm counts (SMD -13.38 [95% CI: -16.33, -10.43] P< 0.0001), total (SMD -7.26 [95% CI: -10.15, -4.36] P< 0.00001) and progressive motility (SMD -6.386 [95% CI: -10.04, -2.73] P= 0.0006), and normally formed sperm (SMD -1.96 [95% CI: -3.29, -0.62] P= 0.004) in CoQ10-treated male subjects compared with untreated/placebo-treated male subjects. Nonetheless, there was a significant inter-study heterogeneity in these studies. Moreover, significantly higher serum testosterone (SMD -0.59 [95% CI: -0.79, -0.40] P< 0.00001) and inhibin B levels (SMD -0.92 [95% CI: -1.47, -0.37] P= 0.001) were recorded in CoQ10-treated subjects compared to untreated/placebo-treated subjects. In addition, CoQ10 supplementation significantly lowered serum LH (SMD 1.77 [95% CI: 1.26, 2.28] P< 0.00001) and FSH concentrations (SMD 1.60 [95% CI: 1.38, 1.81] P< 0.00001). Interestingly, there was no significant inter-study heterogeneity in the hormonal studies. However, CoQ10 supplementation had no significant effect on semen volume (SMD 0.12 [95% CI: -0.13, 0.37] P= 0.34) and sperm concentration (SMD -6.69 [95% CI: -16.28, 2.90] P= 0.17). Our study shows that CoQ10 supplementation increases total sperm count, total and progressive sperm motility, and the proportion of normally formed sperm in association with higher serum testosterone and inhibin B levels. Our study therefore supports the view in the literature of a beneficial use of CoQ10 in male infertility treatment. However, further well-designed RCTs with sufficiently large numbers of subjects are required to reach a final conclusion.

Beeswax Alcohol (BWA, Raydel®) Improved Blood Oxidative Variables and Ameliorated Severe Damage of Zebrafish Kidneys, Testes, and Ovaries Impaired by 24-Week Consumption of a High-Cholesterol and High-Galactose Diet: A Comparative Analysis with Coenzyme Q10.

The present study describes the comparative effect of 24-week supplementation of beeswax alcohol (BWA, Raydel®, 0.5% and 1.0%, wt/wt) and coenzyme Q10 (CoQ10, 0.5% and 1.0%, wt/wt) on plasma oxidative variables and the prevention of organ injury in adult zebrafish subjected to a high-cholesterol (HC, 4%, wt/wt) and -D-galactose (Gal, 30%, wt/wt) diet. Adult zebrafish were fed various HC+Gal diets enriched with either BWA or CoQ10. After 24 weeks of dietary intervention, blood and organs were harvested for subsequent biochemical and histological evaluations. The HC+Gal-elevated plasma oxidative variables were reverted by the consumption of BWA, marked by the lowest plasma malondialdehyde (MDA) level and highest sulfhydryl content. The HC+Gal-impaired zebrafish swimming ability (staggering movement) was substantially recovered by BWA, manifested by a ~three-fold (p < 0.001) enhancement in swimming distance and speed. Also, the intake of BWA affected the morphology of HC+Gal-compromised kidney and induced histological changes by mitigating reactive oxygen species (ROS) production and cellular senescence, which was markedly more effective than the results seen in the CoQ10 group. Likewise, BWA proved effective in preventing HC+Gal-induced testis damage, apparent in the 48.3% (p < 0.05) higher spermatozoa and 26.3% (p < 0.01) reduced interstitial space between the seminiferous tubules. BWA substantially prevented HC+Gal-induced ovary damage by suppressing oxidative stress, lipid deposition and senescence, leading to the restoration of mature vitellogenic oocyte counts. BWA demonstrated a greater ability than CoQ10 to enhance plasma antioxidant status, suppress ROS generation, delay organ aging and alleviate HC+Gal-induced adversity in zebrafish.

Coenzyme Q10 Supplementation Effects on In Vitro Oocyte Maturation, Lipid Peroxidation, and Embryonic Development in Prepubertal and Aging Thai-Holstein Cows.

This study investigated the effects of coenzyme Q10 (CoQ10) supplementation on in vitro oocyte maturation, lipid peroxidation, and embryonic development in prepubertal and aging Thai-Holstein cows. First, we used slaughterhouse-derived oocytes to confirm that CoQ10 (50 μM) significantly enhanced cleavage (53.33% vs. 37.50%) and blastocyst formation rates (46.81% vs. 27.50%). Thereafter, oocytes were collected from four prepubertal and four aging cows via ovum pick-up and matured in vitro with or without CoQ10 supplementation. The follicular development and oocyte quality were assessed. Aging cows exhibited significantly more follicles (24.00 vs. 16.67) and greater oocyte recovery (16.67 vs. 11.67) than prepubertal cows. Additionally, CoQ10 supplementation significantly reduced malondialdehyde levels in aging cows (1.28 vs. 0.61 nmol/mL), indicating reduced lipid peroxidation. Finally, CoQ10 significantly improved cleavage rates in both age groups (prepubertal: 22.50 to 32.50%; aging: 41.71 to 65.00%) and blastocyst formation rates in aging cows (prepubertal: 17.50 to 20.00%; aging: 31.44 to 53.72%). These results suggest that CoQ10 supplementation enhances oocyte maturation and embryonic development, particularly in aging cows, likely by mitigating oxidative stress and supporting mitochondrial function. Therefore, CoQ10 may be a valuable supplement in assisted reproductive technologies for improving reproductive efficiency in cattle breeding programs.

Circulating Glutathione Peroxidase-3 in Elderly-Association with Renal Function, Cardiovascular Mortality, and Impact of Selenium and Coenzyme Q10 Supplementation.

Low-selenium status was associated with impaired renal function, which improved after selenium and coenzyme Q10 supplementation in an RCT. Here, we evaluated serum glutathione peroxidase-3 (GPx3) and its relation to serum selenium, selenoprotein P (SELENOP), renal function, mortality, and the impact of supplementation, which are all important, especially in elderly individuals. In total, 383 study participants (197 receiving selenium yeast and coenzyme Q10 and 186 on a placebo) were evaluated. We applied benchmark dose modelling to determine GPx3 saturation, ANCOVA, Kaplan-Meier, and multivariate Cox proportional regression analyses for mortality evaluations. Selenium and GPx3 activity were modestly correlated. In comparison with SELENOP, GPx3 levelled off at a much lower value, 100 vs. 150 µg Se/L. GPx3 was associated with renal function, but not SELENOP. Supplementation increased glomerular function by ≈23% with an increase in GPx3. Being low in GPx3 displayed twice the risks of mortality in both placebos and active treatments. At serum selenium <100 µg/L, GPx3 activity was dependent on both selenium status and renal function. As renal function is reduced in the elderly, GPx3 is not an appropriate marker of selenium status. Low GPx3 was associated with an increased risk of mortality dependent of selenium status and independent of renal function.

200 Effect of coenzyme Q10 supplementation on bovine oocyte maturation and embryo development

200 Effect of coenzyme Q10 supplementation on bovine oocyte maturation and embryo development

Child Neurology: Five-Year Update on Siblings With Riboflavin Transporter Deficiency: Stable Visual and Neurologic Status With Continued Riboflavin Therapy.

Riboflavin transporter deficiency (RTD), previously referred to as Brown-Vialetto-Van Laere syndrome, is caused by pathogenic variants in the SLC52A1, SLC52A2, or SLC52A3 genes, resulting in RTD types 1, 2, and 3, respectively. Researchers estimate an occurrence of approximately 1 in 1,000,000. There is only one case of type 1 described in medical literature. Type 2 is characterized by muscle weakness in the arms and neck, vision loss, hearing impairment, and sensory ataxia. In type 3, vocal cord paralysis is more common and muscle weakness is more generalized. In 2018, we described a case of a 6-year-old girl with RTD type 2 who made remarkable visual recovery after initiation of treatment with oral riboflavin and coenzyme Q10 supplementation. The patient's younger brother began the same treatment regimen after genetic testing confirmed that he carried the same genetic variant. In this report, we update the visual and neurologic status in these siblings 5 years after our initial report and 7.5 years after initiation of riboflavin treatment.

Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q10 Biosynthesis Disorders.

Disorders of coenzyme Q10 (CoQ10) biosynthesis comprise a group of 11 clinically and genetically heterogeneous rare primary mitochondrial diseases. We sought to delineate clinical, biochemical, and neuroimaging features of these disorders, together with outcomes after oral CoQ10 supplementation and the utility of peripheral blood mononuclear cell (PBMNC) CoQ10 levels in monitoring therapy. This was a retrospective cohort study, registered as an audit at a specialist pediatric hospital (Registration Number: 3318) of 14 patients with genetically confirmed CoQ10 biosynthesis deficiency, including 13 previously unreported cases. We show that oral doses of CoQ10 up to 70 mg/kg/d were needed to ameliorate neurologic features. Additional idebenone was required to control seizures in some cases, and 3 children with neonatal-onset neurologic disease died in early childhood despite receiving high-dose oral CoQ10 from birth. We also demonstrate that early diagnosis and treatment of CoQ10 deficiency with oral supplementation (30 mg/kg/d) can reverse renal manifestations and can completely prevent kidney disease over 10 years of follow-up. PBMNC CoQ10 levels increased after oral CoQ10 supplementation, demonstrating absorption of exogenous CoQ10 into the bloodstream. An early genome-wide diagnostic approach is needed for expeditious diagnosis of CoQ10 biosynthesis disorder because our study demonstrates that there are no pathognomonic blood, muscle, or imaging biomarkers of these diseases. Our findings indicate that earlier diagnosis and treatment with high-dose CoQ10 is key in halting progression of kidney disease or preventing it altogether. This study uses serial PBMNC CoQ10 levels to monitor therapy. Patients with genetically confirmed CoQ10 biosynthesis disorder should receive high-dose oral CoQ10 as soon as possible after presentation, regardless of genetic cause, to prevent disease progression, but parents of children with neonatal or infantile neurologic presentations should be counseled about the poor prognosis.

Renoprotective effects of coenzyme Q10 supplementation in patients with chronic kidney disease: a protocol for a systematic review

IntroductionCoenzyme Q10 (CoQ10) is a fat-soluble vitamin-like quinone. The plasma levels of CoQ10 are reduced in patients with chronic kidney disease (CKD). CoQ10 supplementation can improve mitochondrial function and decrease...

Effect of Coenzyme Q10 Supplementation on Lipid and Glycaemic Profiles: An Umbrella Review.

Coenzyme Q10 (CoQ10) has been suggested as an adjunct therapy for endocrine and metabolic disorders. The aim of this study was to synthesise the evidence for the effect of CoQ10 supplementation on lipid and/or glycaemic alterations, including total cholesterol (TC), LDL- and HDL-cholesterol (LDL-C and HDL-C), lipoprotein a, fasting blood glucose (FBG), haemoglobin A1c (HbA1c), fasting insulin and Homeostatic Model Assessment of Insulin Resistance. A systematic search was conducted in Medline, Scopus, Web of Science and the Cochrane Library from their inception to July 2024. Meta-analyses that evaluated the effect of CoQ10 on the lipid or glycaemic profiles were included. Results were expressed as mean difference (MD) or standardised mean difference (SMD). CoQ10 showed an effect on the glycaemic profile, especially on FBG (MD from -11.21 to -5.2 mg/dL, SMD from -2.04 to -0.17) and on HbA1c (MD from -1.83 to -0.12%, SMD of -0.30). CoQ10 may also have an effect on the lipid profile, such as TC, triglycerides, HDL-C and even LDL-C, although the inconsistency of the results was somewhat higher. Supplementation with CoQ10 may be beneficial, especially in populations with diabetes mellitus or other endocrine and metabolic disorders. It could also have some effect on lipid parameters, which, together with the above, may reduce cardiovascular morbidity and mortality, although this is something that needs further research.

Physical activity and supplementation as alternative methods in migraine prophylaxis -literature review

Migraine is a common and debilitating neurological disorder. It is crucial to realize that migraines are distinguished from other types of headaches. People suffering from migraine are often unable to function normally, neglecting work and daily duties. The associated costs burden not only the patients but also their family and social life. What is more, many psychiatric comorbidities are common in migraine patients. Because of all these factors, preventive treatment is essential because it can decrease migraine frequency and improve quality of life. There are many preventative medications but satisfactory improvement in reducing the frequency of migraine attacks may not be achieved without modification of lifestyle including taking care of physical activity and supplementation. Many studies have shown that moderate physical activity and supplementation of vitamins B2, D, coenzyme Q10 and magnesium has a positive effect on reducing duration and frequency of the migraine attack.

The Effects of Ubiquinone on the Antioxidant System in Male Rats Exposed to Saccharin-Induced the Hepatic Toxicity

Saccharin (Sac) is a widely used artificial sweetener with significant applications in the food industry, pharmaceutical formulations, and tobacco products. Despite its popularity, saccharin has drawn attention due to its potential carcinogenic effects and associations with various health risks, including renal impairment, hepatic dysfunction, obesity, and diabetes. This study aimed to investigate the protective effects of Ubiquinone, or coenzyme Q10 (COQ10), on liver toxicity induced by saccharin, focusing on oxidative stress and antioxidant markers. In this experiment, rats were divided into six groups of ten. The control group received no treatment, while the second group was administered COQ10 at a dosage of 20 mg per kilogram of body weight. The third and fourth groups were given saccharin at 1/10 and 1/20 of the lethal dose 50 (LD50), respectively. The fifth and sixth groups received saccharin at the same dosages as the third and fourth groups, but with additional COQ10 supplementation. All treatments were administered orally for 30 days, after which liver tissues were collected to assess oxidative stress and antioxidant markers. The results revealed that saccharin significantly increased oxidative stress in the liver, as evidenced by elevated levels of malondialdehyde (MDA) and oxidized glutathione (GSSG). Additionally, saccharin-treated groups exhibited a marked decrease in antioxidant markers, including reduced glutathione (GSH) and superoxide dismutase (SOD). However, the groups that received COQ10 alongside saccharin showed significant improvement, with oxidative stress and antioxidant levels nearly returning to those observed in the control group. These findings suggest that saccharin consumption promotes the generation of reactive oxygen species and contributes to liver damage, characterized by necrotic hepatocytes, sinusoidal dilatation, and inflammatory infiltration. The protective effects of COQ10 in mitigating saccharin-induced oxidative stress highlight its potential as a therapeutic agent for preventing liver damage associated with saccharin intake.

Histological Analysis of White Pulp of Spleen Due to Supplementation of Coenzyme Q10 in Immunocompromised Adult Female Albino Wistar Rats

Histological Analysis of White Pulp of Spleen Due to Supplementation of Coenzyme Q10 in Immunocompromised Adult Female Albino Wistar Rats

4-Hydroxybenzoic acid restrains Nlrp3 inflammasome priming and activation via disrupting PU.1 DNA binding activity and direct antioxidation

Reactive oxygen species (ROS) production is considered central to triggering the nucleotide-binding domain-like receptor family pyrin domain containing 3 (Nlrp3) inflammasome activation and the subsequent inflammatory responses. Coenzyme Q10 (CoQ10) plays a critical role in maintaining intracellular ROS homeostasis and inhibiting excessive Nlrp3 inflammasome activation. However, direct supplementation of CoQ10 showed unsatisfactory clinical improvement due to its limited absorption and bioavailability. Therefore, stimulating endogenous CoQ10 biosynthesis by supplementing CoQ10 precursors may provide a more promising therapeutic approach. In this study, we described the role of 4-hydroxybenzoic acid (4-HBA), a precursor of CoQ10, in attenuating excessive inflammatory responses. We found that while supplementation of 4-HBA inhibited the priming and activation of Nlrp3 inflammasome, this effect was independent of its metabolic transformation into CoQ10. 4-HBA itself exhibits antioxidative activities. Furthermore, 4-HBA can disrupt the binding activity of PU.1 on the promoters of Tlr4 and Md2, thereby directly suppressing Nlrp3 inflammasome priming during LPS-induced inflammatory responses. Therefore, strategically utilizing 4-HBA or increasing 4-HBA intake may represent a potential strategy for reducing excessive inflammation.

Evaluation of Antioxidant Effects of Coenzyme Q10 against Hyperglycemia-Mediated Oxidative Stress by Focusing on Nrf2/Keap1/HO-1 Signaling Pathway in the Liver of Diabetic Rats.

Hyperglycemia-induced oxidative stress can damage the liver and lead to diabetes complications. Coenzyme Q10 (CoQ-10) reduces diabetes-related oxidative stress. However, its molecular mechanisms are still unclear. This study aimed to examine CoQ-10's antioxidant capabilities against hyperglycemia-induced oxidative stress in the livers of diabetic rats, specifically targeting the Nrf2/Keap1/ARE signaling pathway. This study was conducted between 2020-2021 at Arak University of Medical Sciences. A total of 30 male adult Wistar rats (8 weeks old) weighing 220-250 g were randomly assigned to five groups (n=6 in each group): control healthy, sesame oil (CoQ-10 solvent), CoQ-10 (10 mg/Kg), diabetic, and diabetic+CoQ-10. Liver oxidative stress indicators, including malondialdehyde, catalase, glutathione peroxidase, and glutathione, were estimated using the spectrophotometry method. Nrf2, Keap1, HO-1, and NQO1 gene expressions were measured using real-time PCR tests in the liver tissue. All treatments were conducted for 6 weeks. Statistical analysis was performed using SPSS software. One-way ANOVA followed by LSD's or Tukey's post hoc tests were used to compare the results of different groups. P<0.05 was considered statistically significant. The findings showed that induction of diabetes significantly increased Keap1 expression (2.1±0.9 folds, P=0.01), and significantly inhibited the mRNA expression of Nrf2 (0.38±0.2 folds, P=0.009), HO-1 (0.27±0.1 folds, P=0.02), and NQO1 (0.26±0.1 folds P=0.01), compared with the healthy group. In the diabetic group, the activity of glutathione peroxidase, catalase enzymes, and glutathione levels was decreased with an increase in malondialdehyde level. CoQ-10 supplementation significantly up-regulated the expressions of Nrf2 (0.85±0.3, P=0.04), HO-1 (0.94±0.2, P=0.04), NQO1 (0.88±0.5, P=0.03) genes, and inhibited Keap1 expression (1.1±0.6, P=0.02). Furthermore, as compared to control diabetic rats, CoQ-10 ameliorated oxidative stress by decreasing malondialdehyde levels and increasing catalase, glutathione peroxidase activities, and glutathione levels in the liver tissues of the treated rats in the treatment group. The findings of this study revealed that CoQ-10 could increase the antioxidant capacity of the liver tissue in diabetic rats by modulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway.

Refractory Epilepsy in Adult Patient With COQ8A Variant Improves With CoQ10 Supplementation: A Case for Exome Sequencing in the ICU.

Describe a case of stroke-like episodes and refractory status epilepticus diagnosed with primary CoQ10 deficiency-4 (COQ10D4) using whole-exome sequencing in the intensive care unit (ICU), with treatment implications. A patient presented to the emergency department with 1 month of progressively worsening focal motor status epilepticus and stroke-like imaging abnormalities. Multiple seizure medications, ketogenic diet, and elective intubation for anesthetic drips failed to achieve sustained seizure freedom. Genetic testing was pursued for prognostic information and identified potential treatment. Whole-exome sequencing revealed compound heterozygous variants of COQ8A, including 1 allele not previously described as pathogenic. The patient's history, imaging, and genetic testing supported a diagnosis of COQ10D4. High-dose coenzyme Q10 supplementation was started with gradual clinical improvement. Whole-exome sequencing is a fast and cost-effective means to diagnose rare neurologic disease in critically ill patients and can uncover treatment options. While primarily used in the neonatal ICU, appropriately selected adult patients may also benefit.

LncRNA DCRT Protects Against Dilated Cardiomyopathy by Preventing NDUFS2 Alternative Splicing by Binding to PTBP1.

Dilated cardiomyopathy is characterized by left ventricular dilation and continuous systolic dysfunction. Mitochondrial impairment is critical in dilated cardiomyopathy; however, the underlying mechanisms remain unclear. Here, we explored the cardioprotective role of a heart-enriched long noncoding RNA, the dilated cardiomyopathy repressive transcript (DCRT), in maintaining mitochondrial function. The DCRT knockout (DCRT-/-) mice and DCRT knockout cells were developed using CRISPR-Cas9 technology. Cardiac-specific DCRT transgenic mice were generated using α-myosin heavy chain promoter. Chromatin coimmunoprecipitation, RNA immunoprecipitation, Western blot, and isoform sequencing were performed to investigate the underlying mechanisms. We found that the long noncoding RNA DCRT was highly enriched in the normal heart tissues and that its expression was significantly downregulated in the myocardium of patients with dilated cardiomyopathy. DCRT-/- mice spontaneously developed cardiac dysfunction and enlargement with mitochondrial impairment. DCRT transgene or overexpression with the recombinant adeno-associated virus system in mice attenuated cardiac dysfunction induced by transverse aortic constriction treatment. Mechanistically, DCRT inhibited the third exon skipping of NDUFS2 (NADH dehydrogenase ubiquinone iron-sulfur protein 2) by directly binding to PTBP1 (polypyrimidine tract binding protein 1) in the nucleus of cardiomyocytes. Skipping of the third exon of NDUFS2 induced mitochondrial dysfunction by competitively inhibiting mitochondrial complex I activity and binding to PRDX5 (peroxiredoxin 5) and suppressing its antioxidant activity. Furthermore, coenzyme Q10 partially alleviated mitochondrial dysfunction in cardiomyocytes caused by DCRT reduction. Our study revealed that the loss of DCRT contributed to PTBP1-mediated exon skipping of NDUFS2, thereby inducing cardiac mitochondrial dysfunction during dilated cardiomyopathy development, which could be partially treated with coenzyme Q10 supplementation.