Coenzyme Q10 ameliorates chemotherapy-induced cognitive impairment in mice: a preclinical study.

BACKGROUND: Among the three most used anticancer drugs, cyclophosphamide, Adriamycin, and 5-Fluorouracil (CAF), the most significant outcome is chemobrain, caused by increased oxidative stress, inflammatory insult, and mitochondrial dysfunction. OBJECTIVE: In this study, endogenous antioxidant coenzyme Q10 (CoQ10) was evaluated for its neuroprotective effects in CICI. MATERIALS AND METHODS: The chemobrain was induced in Swiss albino female mice by administering CAF (40 + 4 + 25 mg/kg) intraperitoneal (i.p.) in three cycles (single injection per week) followed by treatment with CoQ10 (40 mg/kg; p.o.) for up to 3 weeks followed by behavioral, biochemical, molecular and histopathological analysis. RESULTS: Treatment with CoQ10 significantly improved cognition by improving exploring time in novel objects recognition test followed by increasing the time spent in the target quadrant in MWM test as compared to CAF-treated animals. Moreover, CoQ10 demonstrated antioxidant properties by reducing the expression of LPO while increasing levels of GSH, SOD, and catalase as compared to CAF-treated animals. While the levels of AChEs were significantly reduced after CoQ10 treatment in CAF-treated animals. In terms of its mechanism, it effectively counteracted the pro-inflammatory substances (TNF-α and IL-1ß) triggered by CAF while also enhancing the levels of anti-inflammatory markers (IL-10 and Nrf2). Moreover, CoQ10 showed mitochondrial enhancers and it improved the level of Complex (I, II, and IV). Besides that, mitochondrial morphological analysis was done by TEM, and neuronal morphology along with quantification analysis was performed by H&E staining using Image J software to confirm the neuroprotective effect of CoQ10 over CAF-induced cognitive impairment. CONCLUSION: This study suggests CoQ10 can protect the mitochondria by imposing antioxidant, and anti-inflammatory properties, which could be a potential therapy for CICI.

Attenuation of chromium (VI) and arsenic (III)-induced oxidative stress and hepatic apoptosis by phloretin, biochanin-A, and coenzyme Q10 via activation of SIRT1/Nrf2/HO-1/NQO1 signaling.

Heavy metal contamination is an alarming concern on a global scale, as drinking tainted water significantly increases human susceptibility to heavy metals. In a realistic scenario, humans are often exposed to a combination of harmful chemicals rather than a single toxicant. Phloretin (PHL), biochanin-A (BCA), and coenzyme Q10 (CoQ10) are bioactive compounds owning plentiful pharmacological properties. Henceforth, the current research explored the putative energizing effects of selected nutraceuticals in combined chromium (Cr) and arsenic (As) intoxicated Swiss albino mice. Potassium dichromate (75 ppm) and sodium meta-arsenite (100 ppm) were given in the drinking water to induce hepatotoxicity, conjugated with PHL and BCA (50 mg/kg each), and CoQ10 (10 mg/kg) intraperitoneally for 2 weeks. After the statistical evaluation, it was observed that the hepato-somatic index, metal load, and antioxidant activity (lipid peroxidation and protein carbonyl content) increased along with the concomitant decrease in the antioxidants (catalase, glutathione-S-transferase, superoxide dismutase, reduced glutathione, and total thiol) in the Cr and As intoxicated mice. Additionally, light microscopy observations, DNA breakages, decreased silent information regulator 1 (SIRT1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) gene expressions, together with stimulated apoptotic cell death manifested by the increased expressions of caspase 8 and caspase 3, thus, proved consistency with the aforementioned outcomes. Importantly, the treatment with nutraceuticals not only restored the antioxidant activity but also favorably altered the expressions of SIRT1, Nrf2, HO-1, and NQO1 signaling and apoptosis markers. These findings highlight the crucial role of the PHL, BCA, and CoQ10 combination in reducing Cr and As-induced hepatotoxicity in mice. By averting the triggered apoptosis in conjunction with oxidative stress, this combination increases the SIRT1, Nrf2, HO-1, and NQO1 signaling, thereby reassuringly maintaining the cellular equilibrium.

Effects of coenzyme Q10 on orthodontic tooth movement and alveolar bone remodeling in rats.

OBJECTIVES: To evaluate the effects of coenzyme Q10 (CoQ10) on alveolar bone remodeling and orthodontic tooth movement (OTM). MATERIALS AND METHODS: An orthodontic appliance was placed in 42 female Sprague‒Dawley rats were divided into two groups: the orthodontic force (OF) group (n = 21) and the OF + CoQ10 (CoQ10) treatment group (n = 21). Each group was divided into 3 subgroups, and the rats were sacrificed on days 3, 7 and 14. The rats in CoQ10 and OF groups were administered 100 mg/kg b.w./day CoQ10 (in 1 mL/b.w. soybean oil) and 1 mL b.w./day soybean oil, respectively, by orogastric gavage. The OTM was measured at the end of the experiment. The osteoclast, osteoblast and capillary numbers; vascular endothelial growth factor (VEGF), receptor activator nuclear kappa B ligand (RANKL) and osteoprotegrin (OPG) levels in tissue; and total antioxidant status (TAS) and total oxidant status (TOS) in blood were determined. RESULTS: Compared with the OF group, the CoQ10 treatment group exhibited decreased orthodontic tooth movement and osteoclast and capillary numbers. Indeed, the levels of VEGF and RANKL decreased, while the levels of OPG increased except on day 7. Additionally, the CoQ10 treatment group exhibited lower TOS and higher TAS on days 7 and 14 (p < 0.05). Histological findings showed that the morphology of osteoblasts changed in the CoQ10 group; however, there was no significant difference in the number of osteoblasts between the groups (p > 0.05). CONCLUSION: Due to its effect on oxidative stress and inflammation, CoQ10 regulates bone remodeling by inhibiting osteoclast differentiation, promoting osteoblast differentiation and reducing the amount of OTM. CLINICAL RELEVANCE: Considering that OTM may be slowed with the use of CoQ10, topics such as orthodontic treatment duration, orthodontic force activation and appointment frequency should be considered in treatment planning. It is predicted that the use of CoQ10 will support the effectiveness of treatment in clinical applications such as preventing relapse in orthodontic treatment by regulating bone modulation and anchorage methods that suppress/optimize unwanted tooth movement.

Clinical evidence of coenzyme Q10 pretreatment for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis.

BACKGROUND: To quantitatively evaluate the effect of coenzyme Q10 (CoQ10) pretreatment on outcomes of IVF or ICSI in women with diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs). METHODS: Nine databases were comprehensively searched from database inception to November 01, 2023, to identify eligible RCTs. Reproductive outcomes of interest consisted of three primary outcomes and six secondary outcomes. The sensitivity analysis was adopted to verify the robustness of pooled results. RESULTS: There were six RCTs in total, which collectively involved 1529 participants with DOR receiving infertility treatment with IVF/ICSI. The review of available evidence suggested that CoQ10 pretreatment was significantly correlated with elevated clinical pregnancy rate (OR = 1.84, 95%CI [1.33, 2.53], p = 0.0002), number of optimal embryos (OR = 0.59, 95%CI [0.21, 0.96], p = 0.002), number of oocytes retrieved (MD = 1.30, 95%CI [1.21, 1.40], p < 0.00001), and E2 levels on the day of hCG (SMD = 0.37, 95%CI [0.07, 0.66], p = 0.01), along with a reduction in cycle cancellation rate (OR = 0.60, 95%CI [0.44, 0.83], p = 0.002), miscarriage rate (OR = 0.38, 95%CI [0.15, 0.98], p = 0.05), total days of Gn applied (MD = -0.89, 95%CI [-1.37, -0.41], p = 0.0003), and total dose of Gn used (MD = -330.44, 95%CI [-373.93, -286.96], p < 0.00001). The sensitivity analysis indicated that our pooled results were robust. CONCLUSIONS: These findings suggested that CoQ10 pretreatment is an effective intervention in improving IVF/ICSI outcomes for women with DOR. Still, this meta-analysis included relatively limited sample sizes with poor descriptions of their methodologies. Rigorously conducted trials are needed in the future.

Activation of Mitochondria in Mesenchymal Stem Cells by Mitochondrial Delivery of Coenzyme Q10.

The efficacy of mesenchymal stem cell (MSC) transplantation has been reported for various diseases. We previously developed a drug delivery system targeting mitochondria (MITO-Porter) by using a microfluidic device to encapsulate Coenzyme Q10 (CoQ10) on a large scale. The current study aimed to confirm if treatment with CoQ10 encapsulated by MITO-Porter enhanced mitochondrial functions in MSCs, with the potential to improve MSC transplantation therapy. We used highly purified human bone marrow-derived MSCs, described as rapidly expanding clones (RECs), and attempted to control and increase the amount of CoQ10 encapsulated in the MITO-Porter using microfluidic device system. We treated these RECs with CoQ10 encapsulated MITO-Porter, and evaluated its cellular uptake, co-localization with mitochondria, changes in mitochondrial respiratory capacity, and cellular toxicity. There was no significant change in mitochondrial respiratory capacity following treatment with the previous CoQ10 encapsulated MITO-Porter; however, mitochondrial respiratory capacity in RECs was significantly increased by treatment with CoQ10-rich MITO-Porter. Utilization of a microfluidic device enabled the amount of CoQ10 encapsulated in MITO-Porter to be controlled, and treatment with CoQ10-rich MITO-Porter successfully activated mitochondrial functions in MSCs. The MITO-Porter system thus provides a promising tool to improve MSC cell transplantation therapy.

The Scavenging Activity of Coenzyme Q10 Plus a Nutritional Complex on Human Retinal Pigment Epithelial Cells.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q10 (CoQ10), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ10 (Q) to a nutritional antioxidant complex (Nutrof Total®; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H2O2 significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1ß, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1ß gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H2O2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ10 supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR.

Idebenone protects the kidneys of rats with renovascular arterial hypertension by inhibiting oxidative stress and apoptosis.

Here, the protective effect of antioxidant Idebenone (IDB) on renovascular hypertension was studied. The two-kidney one-clip (2K-1C) model of renal hypertension was established. The rats were divided into 3 groups: sham-operation group, 2K-1C renal hypertensive rats' model group and model treated with IDB group. The mean arterial blood pressure (MBP) of rats was measured and pathological condition of kidney was observed by H&E staining. The change of renal damage biomarkers (Cre, BUN, urine proteins), inflammatory factors (IL-6, IL-1ß and TNF-α), oxidative stress ratio and key factors (MDA, SOD and CAT) were assessed by kits. The apoptosis key proteins (BAD, BAX, Caspase9, GSK-3ß) were detected via Western blot. The 2K-1C model of renal hypertension was established. IDB reduced the MBP, Cre, BUN, urine proteins and improved the pathological condition of 2K-1C kidney. IDB restrained the inflammation factors (IL-6, IL-1ß and TNF-α) and oxidative stress in kidney of renal hypertensive rats' model. Besides, IDB suppressed the expression of apoptosis key factors (BAD, BAX, Caspase9, GSK-3ß) in kidney of renal hypertensive rats' model. IDB protects the kidneys of rats with renovascular arterial hypertension by inhibiting inflammation, oxidative stress, and apoptosis. These findings might provide medication guidance for IDB in renovascular arterial hypertension.

HISTOLOGICAL EFFECTS OF CO ENZYME Q10 ON DOXORUBICIN-INDUCED DEFICITS OF CARDIOPULMONARY AXIS IN WHITE ALBINO RATS.

Doxorubicin is the common chemotherapeutic agent that has been harnessed for the treatment of various types of malignancy including the treatment of soft tissue and osteosarcoma and cancers of the vital organs like breast, ovary, bladder, and thyroid. It is also used to treat leukaemia and lymphoma, however, this is an obstacle because of their prominent side effects including cardiotoxicity and lung fibrosis, we do aim to determine the role of CoQ10 as an antioxidant on the impeding the deleterious impacts of doxorubicin on tissue degenerative effects. To do so, 27 rats were subdivided into 3 groups of 9 each; CoQ10 exposed group, Doxorubicin exposed group, and CoQ10 plus Doxorubicin group. At the end of the study, the animals were sacrificed and lungs with hearts were harvested, and slides were prepared for examination under a microscope. The results indicated that doxorubicin induced abnormal cellular structure resulting in damaging cellular structures of the lung and heart while CoQ10 impeded these damaging effects and nearly restoring normal tissue structure. As a result, CoQ10 will maintain normal tissue of the lung and heart.

Effect of Coenzyme Q10 on early wound healing after recession coverage surgery with the modified coronally advanced tunnel technique and a connective tissue graft: A 6-month, triple-blinded, randomized, placebo-controlled pilot trial.

OBJECTIVES: Coenzyme Q10 (CoQ10) or ubiquinone is one of a cell's most important electron carriers during oxidative phosphorylation and many other cellular processes. As a strong anti-oxidant with further anti-inflammatory effects CoQ10 is of potential therapeutical value. The aim of this randomized controlled clinical trial was to investigate the effect of topical CoQ10 on early wound healing after recession coverage surgery using the modified coronally advanced tunnel (MCAT) and palatal connective tissue graft (CTG). MATERIALS AND METHODS: Thirty patients with buccal gingival recessions were evaluated after being randomly allocated to: 1) MCAT and CTG with topical application of a coenzyme Q10 spray for 21 days or 2) MCAT and CTG with placebo spray. Wound healing was evaluated by the early wound healing index (EHI). Patient-reported pain was analyzed by a 100-mm visual analogue scale (VAS) at day 2, 7, 14 and 21 post-surgically. Mean recession coverage, gain of keratinized tissue and esthetic outcomes were assessed at 6 months. RESULTS: EHI and pain scores showed no significant differences. Time to recovery defined as VAS<10 mm was shorter in the test group. Mean root coverage after 6 months was 84.62 ± 26.57% and 72.19 ± 26.30% for test and placebo, p=0.052. Complete root coverage was obtained in 9 (60%) test and in 2 (13.3%) placebo patients. Increase in keratinized tissue width and esthetical outcomes were similar for both groups. CONCLUSION: CoQ10 had no significant effect on early wound healing and on mean root coverage after 6 months. CLINICAL RELEVANCE: Early wound healing: in young healthy patients with no inflammatory oral conditions topical CoQ10 does not improve early healing.

In-vitro and in-vivo studies of two-drug cocktail therapy targeting chemobrain via the Nrf2/NF-κB signaling pathway.

Today, we critically need alternative therapeutic options for chemotherapy-induced cognitive impairment (CICI), often known as chemo brain. Mitochondrial dysfunction and oxidative stress are two of the primary processes that contribute to the development of chemobrain. Therefore, the purpose of this study was to investigate how CoQ10 and berberine shield neurons from chemotherapy-induced damage in in-vitro studies and memory loss in vivo studies. For the in-vitro investigation, we employed SH-SY5Y cell lines, and for the in-vivo study, we used female Swiss albino mice divided into seven different groups. Data from in-vitro studies revealed that treatment with coenzyme Q10 (CoQ10) and berberine improved chemotherapy-induced toxicity by reducing mitochondrial and total cellular ROS, as well as apoptosis-elicited markers (caspase 3 and 9). CoQ10 and berberine therapy inhibited the nuclear translocation of NF-κB and, consequently, the subsequent expressions of NLRP3 and IL-1ß, implying the prevention of inflammasome formation. Furthermore, CoQ10 and berberine therapy boosted Nrf2 levels. This is a regulator for cellular resistance to oxidants. The in vivo results showed that treatment with CoQ10 (40 mg/kg) and berberine (200 mg/kg) improved the behavioral alterations induced by CAF (40/4/25 mg/kg) in both the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. Furthermore, biochemical and molecular evidence revealed the antioxidant, mitochondrial restorative, and anti-inflammatory potential of CoQ10 (40 mg/kg) and berberine (200 mg/kg) against CAF (40/4/25 mg/kg) subjected mice. In addition, the histological analysis using H&E staining and transmission electron microscopy (for mitochondrial morphology) showed that mice treated with the cocktails had an increased number of healthy neurons with intact mitochondria and a reduced presence of autophagic vacuoles in the hippocampal region of the brain. These findings back up our theory about this novel cocktail method for CAF-induced cognitive impairment.

Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity.

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events, particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability, disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the -1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.

Antioxidants and Fertility in Women with Ovarian Aging: A Systematic Review and Meta-Analysis.

Ovarian aging is a major factor for female subfertility. Multiple antioxidants have been applied in different clinical scenarios, but their effects on fertility in women with ovarian aging are still unclear. To address this, a meta-analysis was performed to evaluate the effectiveness and safety of antioxidants on fertility in women with ovarian aging. A total of 20 randomized clinical trials with 2617 participants were included. The results showed that use of antioxidants not only significantly increased the number of retrieved oocytes and high-quality embryo rates but also reduced the dose of gonadotropin, contributing to higher clinical pregnancy rates. According to the subgroup analysis of different dose settings, better effects were more pronounced with lower doses; in terms of antioxidant types, coenzyme Q10 (CoQ10) tended to be more effective than melatonin, myo-inositol, and vitamins. When compared with placebo or no treatment, CoQ10 showed more advantages, whereas small improvements were observed with other drugs. In addition, based on subgroup analysis of CoQ10, the optimal treatment regimen of CoQ10 for improving pregnancy rate was 30 mg/d for 3 mo before the controlled ovarian stimulation cycle, and women with diminished ovarian reserve clearly benefited from CoQ10 treatment, especially those aged <35 y. Our study suggests that antioxidant consumption is an effective and safe complementary therapy for women with ovarian aging. Appropriate antioxidant treatment should be offered at a low dose according to the patient's age and ovarian reserve. This study was registered at PROSPERO as CRD42022359529.

Effectiveness and mechanisms of combined use of antioxidant nutrients in protecting against oxidative stress-induced neuronal loss and related neurological deficits.

BACKGROUND: Oxidative stress is a well-known pathological factor driving neuronal loss and age-related neurodegenerative diseases. Melatonin, coenzyme Q10 and lecithin are three common nutrients with an antioxidative capacity. Here, we examined the effectiveness of them administrated individually and in combination in protecting against oxidative stress-induced neuronal death in vitro, and neurodegenerative conditions such as Alzheimer's disease and associated deficits in vivo. METHODS: Mouse neuroblastoma Neuro-2a (N2a) cells were exposed with H2O2 for 6 h, and subsequently treated with melatonin, coenzyme Q10, and lecithin alone or in combination for further 24 h. Cell viability was assessed using the CCK-8 assay. Eight-week-old male mice were intraperitoneally injected with D-(+)-galactose for 10 weeks and administrated with melatonin, coenzyme Q10, lecithin, or in combination for 5 weeks starting from the sixth week, followed by behavioral tests to assess the effectiveness in mitigating neurological deficits, and biochemical assays to explore the underlying mechanisms. RESULTS: Exposure to H2O2 significantly reduced the viability of N2a cells and increased oxidative stress and tau phosphorylation, all of which were alleviated by treatment with melatonin, coenzyme Q10, lecithin alone, and, most noticeably, by combined treatment. Administration of mice with D-(+)-galactose-induced oxidative stress and tau phosphorylation, brain aging, impairments in learning and memory, anxiety- and depression-like behaviors, and such detrimental effects were mitigated by melatonin, coenzyme Q10, lecithin alone, and, most consistently, by combined treatment. CONCLUSIONS: These results suggest that targeting oxidative stress via supplementation of antioxidant nutrients, particularly in combination, is a better strategy to alleviate oxidative stress-mediated neuronal loss and brain dysfunction due to age-related neurodegenerative conditions.

DHODH Alleviates Heart Failure via the Modulation of CoQ-Related Ferroptotic Inhibition.

BACKGROUND: Heart failure (HF) is a clinical syndrome that seriously endangers human health and quality of life as the terminal stage of cardiovascular diseases. Ferroptosis as a new iron-dependent programmed cell death mode that is closely related to the occurrence and development of cardiovascular diseases. Dihydroorotate dehydrogenase (DHODH) has been found to play a crucial role in inhibiting ferroptosis and improving mitochondrial function, and its expression can be upregulated by estradiol (E2). Recent studies have found that DHODH can inhibit ferroptosis by reducing coenzyme Q (CoQ) to CoQH2. Therefore, this study aims to explore the effect of up-regulation of DHODH on the pathological hypertrophy and fibrosis of heart failure and its mechanisms. METHODS: The mouse heart failure model was established by transverse aortic constriction (TAC), surgery in mice. Two days after the operation, a subcutaneous injection of E2 or the same volume of sesame oil was given for 8 weeks. Then, the left ventricular systolic function related indicators of mice were measured by echocardiography, and the degree of myocardial fibrosis of mice was detected by histological analysis; the expression levels of heart failure markers were detected by quantitative polymerase chain reaction (q-PCR) and western blot (WB) analysis; the morphological changes of mitochondria in cardiac cells of mice were observed by transmission electron microscopy. Cell model were established by stimulating with phenylephrine for 96 hours. Ferroptosis markers were detected by kits and WB analysis. Mitochondrial function was verified by a JC-1 fluorescent probe, and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining. The knockdown results were detected by WB analysis after transfection of small interfering RNA (siRNA) of CoQ. Fer-1 was added as a positive control to verify the ferroptosis-related changes of myocardial cells. RESULTS: In the animal model, we found that E2 treatment alleviates TAC-induced cardiac hypertrophy and fibrosis and suppresses cardiomyocyte ferroptosis by promotes DHODH upregulation in murine cardiomyocytes. In the cell model, DHODH upregulation protects against phenylephrine-induced cardiomyocytes with failure. However, the effect on up-regulating DHODH was inhibited by transfection to down-regulate CoQ expression. CONCLUSIONS: The up-regulation of DHODH could effectively ameliorate the manifestations of heart failure such as myocardial hypertrophy and fibrosis in mice after TAC surgery, inhibit ferroptosis of cardiac myocytes, and ameliorate mitochondrial function. The mechanism involves CoQ-related biological processes.

Evaluating the efficacy of ubiquinol in heart failure patients: a systematic review and meta-analysis.

Aim: We aim to analyze past literature to evaluate the efficacy of coenzyme Q10 (CoQ-10) in the population with heart failure (HF). Methods: A systematic literature search was conducted through MEDLINE (via PubMed) and Cochrane Library. The outcomes analyzed were a reduction in HF-related mortality, an improvement in exercise capacity, and the left ventricular ejection fraction (LVEF). Results: Among 16 studies, CoQ-10 significantly reduced HF-related mortality by 40% and improved exercise capacity in patients with HF, but demonstrated no significant difference in LVEF however, the potential of its efficacy on LVEF could not be ruled out. Conclusion: CoQ-10 significantly enhances exercise capacity and reduces HF-related mortality; however, its impact on patients with reduced LVEF requires further investigation.

[Box: see text].

Protective Effects of Coenzyme Q10 on Testicular Histology in Rats Exposed via Chronic Mosquito Coil Smoke Inhalation.

OBJECTIVE: To determine the preventive effect of coenzyme Q10 (CoQ10) on the testicular histology of rats exposed chronically to mosquito coil smoke. STUDY DESIGN: Experimental study. Place and Duration of the Study: Department of Anatomy, Army Medical College/National University of Medical Sciences, Rawalpindi, Pakistan, from January to December 2020. METHODOLOGY: Thirty male Sprague Dawley rats were divided into three groups of 10 rats each. Group A was the healthy control. Group B rats were exposed to allethrin-based mosquito coil smoke for 12 weeks (4 hours/day). Group C rats received coenzyme Q10 (CoQ10, 10mg/kg/day) through oral gavage, in addition to 12 weeks of mosquito coil smoke exposure (4 hours/day). At the end of the study, testicular histology was compared among three groups including the germinal epithelium height, seminiferous tubule diameter, and testicular capsule thickness, while adjusting for the body weight variations among rats. RESULTS: The rats in Group B, exposed only to mosquito coil smoke showed testicular disruption, characterised by dilated seminiferous tubules (p <0.001), reduced germinal epithelial height (p <0.001), and thickened testicular capsule (p <0.007), as compared to the control group rats. However, the germinal epithelium height (p = 0.73) and testicular capsule thickness (p = 0.31) of rats receiving CoQ10 in addition to mosquito coil smoke inhalation were not significantly different from the control group. CONCLUSION: Prolonged inhalation of allethrin-based mosquito coil smoke can cause testicular disruption among rats. The oral CoQ10 administration can effectively prevent the histomorphological adverse effects on the testis among rats exposed to mosquito coil smoke. KEY WORDS: Allethrin, Coenzyme Q10, Germinal epithelium, Mosquito coil, Seminiferous tubules, Testicular capsule.

Coenzyme Q0 inhibited the NLRP3 inflammasome, metastasis/EMT, and Warburg effect by suppressing hypoxia-induced HIF-1α expression in HNSCC cells.

Coenzyme Q0 (CoQ0), a quinone derivative from Antrodia camphorata, has antitumor capabilities. This study investigated the antitumor effect of noncytotoxic CoQ0, which included NLRP3 inflammasome inhibition, anti-EMT/metastasis, and metabolic reprogramming via HIF-1α inhibition, in HNSCC cells under normoxia and hypoxia. CoQ0 suppressed hypoxia-induced ROS-mediated HIF-1α expression in OECM-1 and SAS cells. Under normoxia and hypoxia, the inflammatory NLRP3, ASC/caspase-1, NFκB, and IL-1ß expression was reduced by CoQ0. CoQ0 reduced migration/invasion by enhancing epithelial marker E-cadherin and suppressing mesenchymal markers Twist, N-cadherin, Snail, and MMP-9, and MMP-2 expression. CoQ0 inhibited glucose uptake, lactate accumulation, GLUT1 levels, and HIF-1α-target gene (HK-2, PFK-1, and LDH-A) expressions that are involved in aerobic glycolysis. Notably, CoQ0 reduced ECAR as well as glycolysis, glycolytic capability, and glycolytic reserve and enhanced OCR, basal respiration, ATP generation, maximal respiration, and spare capacity in OECM-1 cells. Metabolomic analysis using LC-ESI-MS showed that CoQ0 treatment decreased the levels of glycolytic intermediates, including lactate, 2/3-phosphoglycerate, fructose 1,6-bisphosphate, and phosphoenolpyruvate, and increased the levels of TCA cycle metabolites, including citrate, isocitrate, and succinate. HIF-1α silencing reversed CoQ0-mediated anti-metastasis (N-Cadherin, Snail, and MMP-9) and metabolic reprogramming (GLUT1, HK-2, and PKM-2) under hypoxia. CoQ0 prevents cancer stem-like characteristics (upregulated CD24 expression and downregulated CD44, ALDH1, and OCT4) under normoxia and/or hypoxia. Further, in IL-6-treated SG cells, CoQ0 attenuated fibrosis by inhibiting TGF-ß and Collagen I expression and suppressed EMT by downregulating Slug and upregulating E-cadherin expression. Interesting, CoQ0 inhibited the growth of OECM-1 tumors in xenografted mice. Our results advocate CoQ0 for the therapeutic application against HNSCC.

Therapeutic effects of mitoquinol during an acute heat stress challenge in growing barrows.

Study objectives were to determine the effects of mitoquinol (MitoQ, a mitochondrial-targeted antioxidant) on biomarkers of metabolism and inflammation during acute heat stress (HS). Crossbred barrows [n = 32; 59.0 ±â€…5.6 kg body weight (BW)] were blocked by BW and randomly assigned to 1 of 4 environmental-therapeutic treatments: 1) thermoneutral (TN) control (n = 8; TNCon), 2) TN and MitoQ (n = 8; TNMitoQ), 3) HS control (n = 8; HSCon), or 4) HS and MitoQ (n = 8; HSMitoQ). Pigs were acclimated for 6 d to individual pens before study initiation. The trial consisted of two experimental periods (P). During P1 (2 d), pigs were fed ad libitum and housed in TN conditions (20.6 ±â€…0.8 °C). During P2 (24 h), HSCon and HSMitoQ pigs were exposed to continuous HS (35.2 ±â€…0.2 °C), while TNCon and TNMitoQ remained in TN conditions. MitoQ (40 mg/d) was orally administered twice daily (0700 and 1800 hours) during P1 and P2. Pigs exposed to HS had increased rectal temperature, skin temperature, and respiration rate (+1.5 °C, +6.8 °C, and +101 breaths per minute, respectively; P < 0.01) compared to their TN counterparts. Acute HS markedly decreased feed intake (FI; 67%; P < 0.01); however, FI tended to be increased in HSMitoQ relative to HSCon pigs (1.5 kg vs. 0.9 kg, respectively; P = 0.08). Heat-stressed pigs lost BW compared to their TN counterparts (-4.7 kg vs. +1.6 kg, respectively; P < 0.01); however, the reduction in BW was attenuated in HSMitoQ compared to HSCon pigs (-3.9 kg vs. -5.5 kg, respectively; P < 0.01). Total gastrointestinal tract weight (empty tissue and luminal contents) was decreased in HS pigs relative to their TN counterparts (6.2 kg vs. 8.6 kg, respectively; P < 0.01). Blood glucose increased in HSMitoQ relative to HSCon pigs (15%; P = 0.04). Circulating non-esterified fatty acids (NEFA) increased in HS compared to TN pigs (P < 0.01), although this difference was disproportionately influenced by elevated NEFA in HSCon relative to HSMitoQ pigs (251 µEq/L vs. 142 µEq/L; P < 0.01). Heat-stressed pigs had decreased circulating insulin relative to their TN counterparts (47%; P = 0.04); however, the insulin:FI ratio tended to increase in HS relative to TN pigs (P = 0.09). Overall, circulating leukocytes were similar across treatments (P > 0.10). Plasma C-reactive protein remained similar among treatments; however, haptoglobin increased in HS relative to TN pigs (48%; P = 0.03). In conclusion, acute HS exposure negatively altered animal performance, inflammation, and metabolism, which were partially ameliorated by MitoQ.

Heat stress (HS) compromises animal health and productivity, and this causes major economic losses in almost every livestock sector. The negative consequences of HS are thought to originate from intestinal barrier dysfunction and subsequent immune activation. The underlying causes of lost intestinal integrity during HS are likely multifactorial; however, intestinal ischemia, increased accumulation of reactive oxygen species, and the ensuing epithelial oxidative damage might be potential causes. Mitochondria-targeted antioxidants, such as mitoquinol (MitoQ), are probably more effective than traditional dietary antioxidants (i.e., selenium, vitamin E) at alleviating oxidative stress, as they localize and accumulate within the mitochondria, potentiating their antioxidant activity. Thus, the present study aimed to investigate MitoQ's role during a thermal event in growing pigs. Herein, HS increased all body temperature indices, decreased feed intake (FI), and induced substantial body weight (BW) loss. Interestingly, the reduction in FI and BW was less dramatic in pigs receiving MitoQ. Changes in circulating metabolism and the acute phase response were observed due to the HS challenge; however, contrary to our expectations, these changes were not offset by MitoQ administration. Although our results suggest a positive MitoQ effect on growth performance, future studies are needed to corroborate the replicability of this response during HS.

[Coenzyme Q10 alleviates depression-like behaviors in mice with chronic restraint stress by down-regulating the pyroptosis signaling pathway].

OBJECTIVE: To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress (CRS). METHODS: Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low, moderate and high doses (50, 100 and 200 mg/kg, respectively, n=8), VX765 (a caspase-1 specific inhibitor, 50 mg/kg, n=8), or fluoxetine (10 mg/kg, n=8) on a daily basis for 4 weeks, and the changes in depression-like behaviors of the mice were assessed by sugar water preference test, forced swimming test and tail suspension test. The expression of glial fibrillary acidic protein (GFAP) in the hippocampus of the mice was detected using immunohistochemistry, and the number of synaptic spines was determined with Golgi staining. Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus, and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay. RESULTS: Compared with the normal control mice, the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests (P < 0.05), and these depression-like behaviors were obviously improved by treatment with coenzyme Q10, VX765 or FLX. The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines, enhanced expressions of GSDMD-N, caspase-1 and IL-1ß, and increased colocalization of neurons and caspase-1 p10 (all P < 0.05). All these changes were significantly ameliorated in the mouse models after treatment with Q10. CONCLUSION: Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.

Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice.

BACKGROUND: Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, including degeneration of the articular cartilage, alterations in subchondral bone (SCB) morphology, and inflammation of the synovium. METHODS: We investigated the prevalence of primary OA in aged, genetically diverse UM-HET3 mice. Articular cartilage (AC) integrity and SCB morphology were assessed in 182 knee joints of 22-25 months old mice using the Osteoarthritis Research Society International (OARSI) scoring system and micro-CT, respectively. Additionally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging. RESULTS: Aged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13, inducible nitric oxide synthase, and the NLR family pyrin domain containing-3 inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and ß-galactosidase, also correlated with AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density. Notably, MB and MitoQ treatments influenced the disease's progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance. CONCLUSIONS: Our study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.