Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart.

Elevated intracellular sodium Nai adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Nai decreases Gibb's free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH2, which are all reversed on lowering Nai to baseline levels. Pseudo hypoxia and stabilization of HIF-1α is observed despite normal tissue oxygenation. Inhibition of mitochondrial Na/Ca-exchange with CGP-37517 or treatment with the mitochondrial ROS scavenger MitoQ prevents the metabolic alterations during Nai elevation. Elevated Nai plays a reversible role in the metabolic and functional changes and is a novel therapeutic target to correct metabolic dysfunction in heart failure.

Anticancer Effects of Mitoquinone via Cell Cycle Arrest and Apoptosis in Canine Mammary Gland Tumor Cells.

Treating female canine mammary gland tumors is crucial owing to their propensity for rapid progression and metastasis, significantly impacting the overall health and well-being of dogs. Mitoquinone (MitoQ), an antioxidant, has shown promise in inhibiting the migration, invasion, and clonogenicity of human breast cancer cells. Thus, we investigated MitoQ's potential anticancer properties against canine mammary gland tumor cells, CMT-U27 and CF41.Mg. MitoQ markedly suppressed the proliferation and migration of both CMT-U27 and CF41.Mg cells and induced apoptotic cell death in a dose-dependent manner. Furthermore, treatment with MitoQ led to increased levels of pro-apoptotic proteins, including cleaved-caspase3, BAX, and phospho-p53. Cell cycle analysis revealed that MitoQ hindered cell progression in the G1 and S phases in CMT-U27 and CF41.Mg cells. These findings were supported using western blot analysis, demonstrating elevated levels of cleaved caspase-3, a hallmark of apoptosis, and decreased expression of cyclin-dependent kinase (CDK) 2 and cyclin D4, pivotal regulators of the cell cycle. In conclusion, MitoQ exhibits in vitro antitumor effects by inducing apoptosis and arresting the cell cycle in canine mammary gland tumors, suggesting its potential as a preventive or therapeutic agent against canine mammary cancer.

Coenzyme Q10 prevents RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways.

Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.

Coenzyme Q10 mitigates cadmium cardiotoxicity by downregulating NF-κB/NLRP3 inflammasome axis and attenuating oxidative stress in mice.

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1ß, MCP-1, JNK1, and TGF-ß in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.

Oral administration of coenzyme Q10 ameliorates memory impairment induced by nicotine-ethanol abstinence through restoration of biochemical changes in male rat hippocampal tissues.

Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ10) is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ10 treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ10 treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ10 was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ10 treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.

Discovering the Potential Value of Coenzyme Q10 as an Adjuvant Treatment in Patients With Depression.

PURPOSE/BACKGROUND: Depressive disorder or mental cold is the most common mental disorder, and depression exists all over the world and in all countries and cultures. The results of several studies have shown that using compounds with antioxidant properties has been fruitful in patients with depression. Coenzyme Q10 (CoQ10) is a fat-soluble antioxidant and exerts its antioxidant effect by directly neutralizing free radicals or reducing tocopherol and preventing the inhibition of mitochondrial activity because of oxidative stress. This study aimed to investigate the effects of oral CoQ10 in patients with depression as an adjunctive treatment. METHODS/PROCEDURES: Sixty-nine patients with moderate and severe depression were randomly divided into 2 CoQ10 groups (36) and placebo (33). The first group of patients received CoQ10 supplements at a dose of 200 mg daily for 8 weeks along with standard interventions and treatments for depression, and the second group received standard treatments for depression along with a placebo. The change in the score of Montgomery-Åsberg Depression Rating Scale depression scale was evaluated 4 and 8 weeks after the intervention. Also, at baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity, total thiol groups, nitric oxide, malondialdehyde, and interleukin 6 were assessed. FINDINGS/RESULTS: The changes in the depression score at the end of the study showed that, in the group receiving the CoQ10 supplement after 8 weeks, there was a reduction in depression symptoms, which was statistically significant compared with before the start of the study Meanwhile, no significant changes were observed in the patients of the placebo group in terms of symptom reduction. Compared with baseline and the placebo condition, serum levels of nitric oxide and total thiol groups significantly decreased and increased, respectively. Also, no statistically significant changes were observed for interleukin 6, malondialdehyde, and total antioxidant capacity. IMPLICATIONS/CONCLUSIONS: A dose of 200 mg of CoQ10 supplement daily for 8 weeks can reduce depression and fatigue, as well as improve the quality of life of patients with depression. In addition, CoQ10 can significantly improve inflammation and oxidative stress status in patients with depression.

Ruixingdingia sedimenti gen. nov., sp. nov., a novel taxon within the family Paracoccaceae isolated from sediment of Qiantang River.

A Gram-stain-negative bacterium, designated LG-4T, was isolated from sediment of Qiantang River in Zhejiang Province, PR China. Cells were strictly aerobic, non-spore-forming, non-motile and short-rod-shaped (1.0-1.2 µm long and 0.7-0.8 µm wide). Growth occurred at 15-42 °C (optimum, 30 °C), at pH 5.0-9.0 (pH 7.0) and at 0-2.0 % (w/v) NaCl (optimum, 0.5 % NaCl). Strain LG-4T showed 95.75-96.90 % 16S rRNA gene sequence similarity to various type strains of the genera Tabrizicola, Pseudotabrizicola, Phaeovulum, Rhodobacter and Wagnerdoeblera of the family Paracoccaceae, and the most closely related strain was Tabrizicola soli ZQBWT (96.90 % similarity). The phylogenomic tree showed that strain LG-4T clustered in the family Paracoccaceae and was positioned outside of the clade composed of the genera Wagnerdoeblera and Falsigemmobacter. The average nucleotide identity and digital DNA-DNA hybridization values between strain LG-4T and the related type strains were in the range of 74.19-77.56 % and 16.70-25.80 %, respectively. The average amino acid identity (AAI) values between strain LG-4T and related type strains of the family Paracoccaceae were 60.94-69.73 %, which are below the genus boundary (70 %). The evolutionary distance (ED) values between LG-4T and the related genera of the family Paracoccaceae were 0.21-0.34, which are within the recommended standard (≥0.21-0.23) for defining a novel genus in the family Paracoccaceae. The predominant cellular fatty acids were C18 : 1 ω7c, C19 : 0 cyclo ω8c, C18 : 0 and C16 : 0, the isoprenoid quinone was Q-10, and the major polar lipids were phospholipid, phosphatidylglycerol, phosphatidylcholine, aminolipid and two unknown polar lipids. The genome size was 4.7 Mb with 68.6 mol% G+C content. On the basis of distinct phylogenetic relationships, low AAI values and high ED values, and differential phenotypic, physiological and biochemical characteristics, strain LG-4T represents a novel species of a new genus in the family Paracoccaceae, for which the name Ruixingdingia sedimenti gen. nov., sp. nov. is proposed. The type strain is LG-4T (=MCCC 1K08849T=KCTC 8136T).

Coenzyme Q10 and Autoimmune Disorders: An Overview.

Some 90 autoimmune disorders have been described in medical literature, affecting most of the tissues within the body. Autoimmune disorders may be difficult to treat, and there is a need to develop novel therapeutic strategies for these disorders. Autoimmune disorders are characterised by mitochondrial dysfunction, oxidative stress, and inflammation; there is therefore a rationale for a role for coenzyme Q10 in the management of these disorders, on the basis of its key role in normal mitochondrial function, as an antioxidant, and as an anti-inflammatory agent. In this article, we have therefore reviewed the potential role of CoQ10, in terms of both deficiency and/or supplementation, in a range of autoimmune disorders.

The mitochondria-targeted antioxidant MitoQ ameliorates inorganic arsenic-induced DCs/Th1/Th2/Th17/Treg differentiation partially by activating PINK1-mediated mitophagy in murine liver.

Inorganic arsenic is a well-established environmental toxicant linked to acute liver injury, fibrosis, and cancer. While oxidative stress, pyroptosis, and ferroptosis are known contributors, the role of PTEN-induced kinase 1 (PINK1)-mediated mitophagy in arsenic-induced hepatic immunotoxicity remains underexplored. Our study revealed that acute arsenic exposure prompts differentiation of hepatic dendritic cells (DCs) and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells, alongside increased transcription factors and cytokines. Inorganic arsenic triggered liver redox imbalance, leading to elevated alanine transaminase (ALT), hydrogen peroxide (H2O2), malondialdehyde (MDA), and activation of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway. PINK1-mediated mitophagy was initiated, and its inhibition exacerbates H2O2 accumulation while promoting DCs/Th1/Th2/Treg differentiation in the liver of arsenic-exposed mice. Mitoquinone (MitoQ) pretreatment relieved arsenic-induced acute liver injury and immune imbalance by activating Nrf2/HO-1 and PINK1-mediated mitophagy. To our knowledge, this is the first report identifying PINK1-mediated mitophagy as a protective factor against inorganic arsenic-induced hepatic DCs/Th1/Th2 differentiation. This study has provided new insights on the immunotoxicity of inorganic arsenic and established a foundation for exploring preventive and therapeutic strategies targeting PINK1-mediated mitophagy in acute liver injury. Consequently, the application of mitochondrial antioxidant MitoQ may offer a promising treatment for the metalloid-induced acute liver injury.

Hedgehog pathway inhibitors for locally advanced and metastatic basal cell carcinoma: A real-world single-center retrospective review.

Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50-60% response rate. Long-term toxicity includes muscle spasms and weight loss leading to dose decreases. This retrospective chart review also investigates the impact of CoQ10 and calcium supplementation in patients treated with HHI drugs at a single academic medical center from 2012 to 2022. We reviewed the charts of adult patients diagnosed with locally advanced or metastatic BCC treated with vismodegib or sonidegib primarily for progression-free survival (PFS). Secondary objectives included overall survival, BCC-specific survival, time to and reasons for discontinuation, overall response rate, safety and tolerability, use of CoQ10 and calcium supplements, and insurance coverage. Of 55 patients assessable for outcome, 34 (61.8%) had an overall clinical benefit, with 25 (45.4%) having a complete response and 9 (16.3%) a partial response. Stable disease was seen in 14 (25.4%) and 7 (12.7%) progressed. Of the 34 patients who responded to treatment, 9 recurred. Patients who were rechallenged with HHI could respond again. The median overall BCC-specific survival rate at 5 years is 89%. Dose reductions or discontinuations for vismodegib and sonidegib occurred in 59% versus 24% of cases, or 30% versus 9% of cases, respectively. With CoQ10 and calcium supplementation, only 17% required a dose reduction versus 42% without. HHI is highly effective for treating advanced BCC but may require dosing decreases. Sonidegib was better tolerated than vismodegib. CoQ10 and calcium supplementation can effectively prevent muscle spasms.

MitoQ protects against carbon tetrachloride-induced hepatocyte ferroptosis and acute liver injury by suppressing mtROS-mediated ACSL4 upregulation.

Ferroptosis has been shown to be involved in carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The mitochondrion-targeted antioxidant MitoQ can eliminate the production of mitochondrial reactive oxygen species (mtROS). This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone alleviated CCl4-induced hepatic lipid peroxidation and ALI. ACSL4 knockdown inhibited oxidized lipids in CCl4-exposed human hepatocytes. Moreover, CCl4 exposure decreased the mitochondrial membrane potential and OXPHOS subunit levels and increased the mtROS level in HepG2 cells. Correspondingly, MitoQ pretreatment inhibited the upregulation of ACSL4 in CCl4-evoked mouse livers and HepG2 cells. MitoQ attenuated lipid peroxidation in vivo and in vitro after CCl4 exposure. Finally, MitoQ pretreatment alleviated CCl4-induced hepatocytic ferroptosis and ALI. These findings suggest that MitoQ protects against hepatocyte ferroptosis in CCl4-induced ALI via the mtROS-ACSL4 pathway.

Effect of butylphthalide combined with idebenone on vascular dementia: A retrospective observational analysis.

To explore the efficacy and safety of butylphthalide combined with idebenone in the treatment of vascular dementia. The clinical data of 126 patients with vascular dementia who were admitted to our hospital between March 2021 and February 2023 were retrospectively reviewed. Among them, 62 patients received butylphthalide alone (single group) and 64 patients received butylphthalide combined with idebenone (combined group). Cognitive function scores, serum inflammatory factor levels, oxidative stress index levels, and incidence of adverse reactions were compared between the 2 groups before and after treatment. After treatment, the Hasegawa Dementia Scale, Mini Mental State Examination Scale, and activities of daily living scores in both groups were higher than before treatment, and the scores in the combined group were higher than before treatment (P < .05). After treatment, the levels of serum C-reactive protein, tumor necrosis factor-α, and interleukin 6 in both groups were lower than those before treatment, and those in the combined group were lower than those in the simple group (P < .05). After treatment, the levels of serum glutathione peroxidase and superoxide dismutase in the 2 groups were higher than those before treatment, and the level of malondialdehyde was lower than that before treatment. The levels of serum glutathione peroxidase and superoxide dismutase in the combined group were higher than those in the simple group, and the level of malondialdehyde was lower than that in the simple group (P < .05). There was no significant difference in the incidence of adverse reactions between the combined group (6.25%) and the simple group (3.23%) (P > .05). Compared with butylphthalide alone, intervention of butylphthalide combined with idebenone on vascular dementia can effectively reduce the degree of inflammatory and oxidative stress reactions, improve cognitive function, and promote the ability to perform activities of daily living in a safe manner.

Investigating the individual and combined effects of coenzyme Q10 and vitamin C on CLP-induced cardiac injury in rats.

Sepsis-induced cardiac injury represents a major clinical challenge, amplifying the urgency for effective therapeutic interventions. This study aimed to delve into the individual and combined prophylactic effects of Vitamin C (Vit C) and Coenzyme Q10 (CoQ10) against inflammatory heart injury in a cecal ligation and puncture (CLP) induced polymicrobial sepsis rat model. Thirty adult female Sprague-Dawley rats were randomly divided into five groups: Control, CLP, Vitamin C, CoQ10, and Vit C + CoQ10, each consisting of six rats. Treatments were administered orally via gavage for 10 days prior to the operation. Eighteen hours post-sepsis induction, the animals were euthanized, and specimens were collected for analysis. The study examined variations in oxidative (TOS, OSI, MDA, MPO) and antioxidative markers (TAS, SOD, CAT, GSH), histopathological changes, inflammatory cytokine concentrations (TNF-α, IL-1ß), nitric oxide (NO) dynamics, and cardiac indicators such as CK-MB. Impressively, the combined regimen markedly diminished oxidative stress, and antioxidative parameters reflected notable enhancements. Elevated NO levels, a central player in sepsis-driven inflammatory cascades, were effectively tempered by our intervention. Histological examinations corroborated the biochemical data, revealing diminished cardiac tissue damage in treated subjects. Furthermore, a marked suppression in pro-inflammatory cytokines was discerned, solidifying the therapeutic potential of our intervention. Interestingly, in certain evaluations, CoQ10 exhibited superior benefits over Vit C. Collectively, these findings underscore the potential therapeutic promise of Vit C and CoQ10 combination against septic cardiac injuries in rats.

Antioxidative Stress-Induced Destruction to Cochlear Cells Caused by Blind Antioxidant Therapy.

OBJECTIVE: Verification that blind and excessive use of antioxidants leads to antioxidant stress which exacerbates cochlear cell damage. STUDY DESIGN: Basic research. SETTING: The Third Affiliated Hospital of Sun Yat-Sen University. METHODS: We compared and quantified hair cell-like house ear institute-organ of corti 1 (HEI-OC1) cell density, cell viability, and apoptosis caused by different concentrations of N-acetylcysteine (NAC) via Hoechst staining, Cell Counting Kit 8, Hoechst with propidium iodide staining, and Annexin V with propidium iodide (PI) staining. Apoptosis induced by high concentrations of M40403 and coenzyme Q10 in cochlear explants was analyzed and compared by cochlear dissection and activated caspase 3 labeling. RESULTS: With the increase of NAC concentration (0-1000 µmol/L), cell density decreased consequently and reached the lowest at 1000 µmol/L (****P ≤ .0001). Cell viability is also declining (**P < .01). The number of Annexin V-fluorescein isothiocyanate-labeled cells and PI-labeled cells increased with increasing NAC concentration after treatment of HEI-OC1 cells for 48 hours. The proportion of apoptotic cells also rose (*P < .05, **P < .01). Cochlear hair cells (HCs) treated with low concentrations of M40403 and coenzyme Q10 for 48 hours showed no damage. When the concentrations of M40403 and coenzyme Q10 were increased (concentrations＞30 µmol/L), HC damage began, followed by a dose-dependent increase in HC loss (*P < .001, **P < .0001). Activated caspase-3 was clearly apparent in cochlear explants treated with 50 µmol/L M40403 and coenzyme Q10 compared with cochlear explants without added M40403 and coenzyme Q10. CONCLUSION: These experimental results suggest that inappropriate application of antioxidants can cause severe damage to normal cochlear HCs.

Idebenone Exerts anti-Triple Negative Breast Cancer Effects via Dual Signaling Pathways of GADD45 and AMPK.

Idebenone, a mitochondrial regulator, has exhibited anti-cancer activity in neurogenic and prostate tumor cells; however, its efficacy and specific targets in the treatment of triple-negative breast cancer (TNBC) remain unclear. This study aims to evaluate the potential of Idebenone as a therapeutic agent for TNBC. TNBC cell lines and Xenograft mouse models were used to assess the effect of Idebenone on TNBC both in vitro and in vivo. To investigate the underlying mechanism of Idebenone's effect on TNBC, cell viability assay, transwell invasion assay, cell cycle analysis, apoptosis assay, mitochondrial membrane potential assay, immunofluorescence staining, and transcriptome sequencing were utilized. The results showed that Idebenone impeded the proliferation, colony formation, migration, and invasion of TNBC cells, suppressed apoptosis, and halted the cell cycle in the G2/M phase. The inhibitory effect of Idebenone on TNBC was associated with the GADD45/CyclinB/CDK1 signaling pathway. By disrupting the mitochondrial membrane potential (MMP) and promoting mitophagy, Idebenone promoted cell autophagy through the AMPK/mTOR pathway, thus further suppressing the proliferation of TNBC cells. Furthermore, we found that Idebenone inhibited the development of TNBC in vivo. In conclusion, Idebenone may be a promising therapeutic option for TNBC as it is capable of inducing autophagy and apoptosis.

Involvement of Nrf2-PPAR-γ signaling in Coenzyme Q10 protecting effect against methotrexate-induced testicular oxidative damage.

Studies have identified Coenzyme Q10 (CoQ10) as a promising agent in improving idiopathic male infertility; however, its role in chemically or environmentally induced testicular dysfunction is not well-established. We investigated the potential of CoQ10 to attenuate methotrexate (MTX)-induced testicular damage and to identify molecular targets of CoQ10 effects. Wistar rats received a single intraperitoneal dose of 20 mg/kg MTX on the fifth day of the 10-day experimental protocol. 100 mg/kg CoQ10 was given orally daily for ten days, alone or combined with MTX. The testes of MTX-treated animals showed thickened tunica albuginea, distortion of seminiferous tubules with a marked reduction of germinal lining, a few primary spermatocytes with no spermatozoa, apoptotic cells, congested sub-capsular and interstitial blood vessels, and interstitial edema. Reduction of reproductive hormones and increased oxidative, inflammatory, and apoptotic biomarkers levels were also seen in the MTX-treated rats. CoQ10 + MTX-treated rats were protected against MTX-induced testicular histological changes and showed improvement in testosterone, luteinizing-, and follicle-stimulating hormone serum levels compared to the MTX group. The testes of the CoQ10 + MTX-treated rats showed reduced malondialdehyde, myloperoxidase, tumor necrosis factor -α, interleukin-6 and -1ß and Bax: Bcl2 ratio and enhanced glutathione, and catalase compared to MTX alone. CoQ10 enhanced MTX-induced downregulation of Nrf2 and PPAR-γ signaling and modulated its downstream targets, the inducible nitric oxide synthase, NF-κB, Bax, and Bcl2. In conclusion, CoQ10 targeted the Nrf2-PPAR-γ signaling loop and its downstream pathways, mitigating MTX-induced oxidative stress-related damages and alleviating the testicular dysfunction MTX caused. Our data suggest Nrf2-PPAR-γ signaling as a potential therapeutic target in testicular toxicity, where oxidative stress, inflammation, and apoptosis trigger damage.

The role of CoQ10 in embryonic development.

Coenzyme Q10 (CoQ10) is a natural component widely present in the inner membrane of mitochondria. CoQ10 functions as a key cofactor for adenosine triphosphate (ATP) production and exhibits antioxidant properties in vivo. Mitochondria, as the energy supply center of cells, play a crucial role in germ cell maturation and embryonic development, a complicated process of cell division and cellular differentiation that transforms from a single cell (zygote) to a multicellular organism (fetus). Here, we discuss the effects of CoQ10 on oocyte maturation and the important role of CoQ10 in the growth of various organs during different stages of fetal development. These allowed us to gain a deeper understanding of the pathophysiology of embryonic development and the potential role of CoQ10 in improving fertility quality. They also provide a reference for further developing its application in clinical treatments.

The role of coenzyme Q10 as a preventive and therapeutic agent for the treatment of cancers.

Currently, several options are available for the prevention and treatment of cancers; however, many limitations remain with these approaches. Recently, antioxidants have become important preventive and therapeutic alternatives with few adverse events and minimum cost. Coenzyme Q10 (CoQ10) is a naturally occurring component that performs an anticancer function by reducing oxidative stress. CoQ10 supplementation as an adjuvant therapy offers more progress in the elimination and development of cancers. This review aimed to critically assess and summarize the implication of CoQ10 in cancers, highlighting possible mechanisms, and future directions of research for the standardization of the current regimen for cancer prevention and treatment.

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview.

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Efficacy of coenzyme Q10 and curcumin on antioxidant enzyme activity and hippocampal alteration following exposure to cyclophosphamide in male rat.

Coenzyme Q10 (KQ10) and curcumin (KUR) supplements are extensively used for their potential antioxidant, anticancer, and antiapoptotic properties. The present study investigated the neuroprotective potential of KQ10 and KUR against the side effect of cyclophosphamide (SF) (150 mg/kg) on the hippocampus of male Wistar albino rats. Forty-nine 10-12 weeks old rats were randomly divided into seven groups: control, olive oil (OL), SF, KQ10, KUR, SF+KQ10, and SF+KUR. Our biochemical finding showed a significant decrease in superoxide dismutase (SOD) level in the SF group compared to the control group (p < 0.05). There was also a significant reduction in the total number of the hippocampal pyramidal neurons in the CA1, CA2, and CA1-3 regions in the SF group compared to the control group (p < 0.05). In the SF+KQ10 group, we found a significant increase in serum SOD level and the total number of the hippocampal pyramidal neurons in the CA1, CA2, and CA1-3 regions compared to the SF group (p < 0.05). Immunohistochemical and histopathological examination exhibited noteworthy findings in the hippocampus tissues. Our findings showed that KQ10 administration significantly mitigated the hippocampal alteration caused by SF through enhancing antioxidant enzyme activity and reducing apoptosis. However, we found no protective activity of KUR on the hippocampus tissue, which may be due to its weak antioxidative activity.