Combination of trimetazidine and coenzyme Q10 for the treatment of acute viral myocarditis: a systematic review and meta-analysis.

INTRODUCTION: Coenzyme Q10 (CoQ10) is considered to be beneficial for patients with acute viral myocarditis (AVM). In addition, trimetazidine may be also beneficial to patients with AVM by promoting cardiac energy metabolism. This systematic review and meta-analysis examined the efficacy and safety of combining trimetazidine and CoQ10 with respect to CoQ10 alone in patients suffering from AVM. METHODOLOGY: PubMed, Embase, the Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched for relevant randomized controlled trials (RCTs). An analysis of random effects was employed to combine the results. RESULTS: Sixteen RCTs that included 1,364 patients with AVM contributed to the meta-analysis. Overall, 687 patients received the combined treatment, while 677 received the CoQ10 alone for a duration of 2-12 weeks (mean: 5.2 weeks). In contrast to monotherapy with CoQ10, combined treatment with trimetazidine and CoQ10 significantly improved overall therapy effectiveness (risk ratio [RR]: 1.19, 95% confidence interval [CI]: 1.13 to 1.24, p < 0.001; I2 = 0%). Differences in study parameters such as the incidence of heart failure upon admission, dosage of CoQ10, or length of treatment did not significantly alter the outcomes (p for all subgroup analyses > 0.05). The combined treatment was associated with improved myocardial enzyme levels and recovery of cardiac systolic function as compared to CoQ10 alone (p all < 0.05). In addition, trimetazidine combined with CoQ10 caused no greater increase in adverse events than CoQ10 alone. CONCLUSIONS: Trimetazidine combined with CoQ10 is an effective and safe treatment for AVM.

[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.

Evaluation of the protective effect of coenzyme Q10 on hepatotoxicity caused by acute phosphine poisoning.

Background: Aluminum phosphide (AlP) poisoning is prevalent in numerous countries, resulting in high mortality rates. Phosphine gas, the primary agent responsible for AlP poisoning, exerts detrimental effects on various organs, notably the heart, liver and kidneys. Numerous studies have documented the advantageous impact of Coenzyme Q10 (CoQ10) in mitigating hepatic injuries. The objective of this investigation is to explore the potential protective efficacy of CoQ10 against hepatic toxicity arising from AlP poisoning. Method: The study encompassed distinct groups receiving almond oil, normal saline, exclusive CoQ10 (at a dosage of 100 mg/kg), AlP at 12 mg/kg; LD50 (lethal dose for 50%), and four groups subjected to AlP along with CoQ10 administration (post-AlP gavage). CoQ10 was administered at 10, 50, and 100 mg/kg doses via Intraparietal (ip) injections. After 24 h, liver tissue specimens were scrutinized for mitochondrial complex activities, oxidative stress parameters, and apoptosis as well as biomarkers such as aspartate transaminase (AST) and alanine transaminase (ALT). Results: AlP induced a significant decrease in the activity of mitochondrial complexes I and IV, as well as a reduction in catalase activity, Ferric Reducing Antioxidant Power (FRAP), and Thiol levels. Additionally, AlP significantly elevated oxidative stress levels, indicated by elevated reactive oxygen species (ROS) production, and resulted in the increment of hepatic biomarkers such as AST and ALT. Administration of CoQ10 led to a substantial improvement in the aforementioned biochemical markers. Furthermore, phosphine exposure resulted in a significant reduction in viable hepatocytes and an increase in apoptosis. Co-treatment with CoQ10 exhibited a dose-dependent reversal of these observed alterations. Conclusion: CoQ10 preserved mitochondrial function, consequently mitigating oxidative damage. This preventive action impeded the progression of heart cells toward apoptosis.

Comparing the efficacy of concomitant treatment of resistance exercise and creatine monohydrate versus multiple individual therapies in age related sarcopenia.

Aging-related sarcopenia is a degenerative loss of strength and skeletal muscle mass that impairs quality of life. Evaluating NUDT3 gene and myogenin expression as new diagnostic tools in sarcopenia. Also, comparing the concomitant treatment of resistance exercise (EX) and creatine monohydrate (CrM) versus single therapy by EX, coenzyme Q10 (CoQ10), and CrM using aged rats. Sixty male rats were equally divided into groups. The control group, aging group, EX-treated group, the CoQ10 group were administered (500 mg/kg) of CoQ10, the CrM group supplied (0.3 mg/kg of CrM), and a group of CrM concomitant with resistance exercise. Serum lipid profiles, certain antioxidant markers, electromyography (EMG), nudix hydrolase 3 (NUDT3) expression, creatine kinase (CK), and sarcopenic index markers were measured after 12 weeks. The gastrocnemius muscle was stained with hematoxylin-eosin (H&E) and myogenin. The EX-CrM combination showed significant improvement in serum lipid profile, antioxidant markers, EMG, NUDT3 gene, myogenin expression, CK, and sarcopenic index markers from other groups. The NUDT3 gene and myogenin expression have proven efficient as diagnostic tools for sarcopenia. Concomitant treatment of CrM and EX is preferable to individual therapy because it reduces inflammation, improves the lipid serum profile, promotes muscle regeneration, and thus has the potential to improve sarcopenia.

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.

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.

CoQ10 targeted hippocampal ferroptosis in a status epilepticus rat model.

Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.

Coenzyme Q10 in atherosclerosis.

Atherosclerotic disease is a chronic disease that predominantly affects the elderly and is the most common cause of cardiovascular death worldwide. Atherosclerosis is closely related to processes such as abnormal lipid transport and metabolism, impaired endothelial function, inflammation, and oxidative stress. Coenzyme Q10 (CoQ10) is a key component of complex Ⅰ in the electron transport chain and an important endogenous antioxidant that may play a role in decelerating the progression of atherosclerosis. Here, the different forms of CoQ10 presence in the electron transport chain are reviewed, as well as its physiological role in regulating processes such as oxidative stress, inflammatory response, lipid metabolism and cellular autophagy. It was also found that CoQ10 plays beneficial effects in atherosclerosis by mitigating lipid transportation, endothelial inflammation, metabolic abnormalities, and thrombotic processes from the perspectives of molecular mechanisms, animal experiments, and clinical evidence. Besides, the combined use of CoQ10 with other drugs has better synergistic therapeutic effects. It seems reasonable to suggest that CoQ10 could be used in the treatment of atherosclerotic cardiovascular diseases while more basic and clinical studies are needed.

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival.

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related deaths. Increased activity of the epidermal growth factor receptor (EGFR) is often observed in pancreatic cancer, and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration. Nevertheless, erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes. We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential (Δψm), facilitate tumor cell uptake of Δψm-sensitive agents, disrupt mitochondrial homeostasis, and subsequently trigger tumor cell death. Erlotinib has not been tested for this effect. AIM: To determine whether erlotinib can elevate Δψm and increase tumor cell uptake of Δψm-sensitive agents, subsequently triggering tumor cell death. METHODS: Δψm-sensitive fluorescent dye was used to determine how erlotinib affects Δψm in pancreatic adenocarcinoma (PDAC) cell lines. The viability of conventional and patient-derived primary PDAC cell lines in 2D- and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone (MitoQ), a Δψm-sensitive MitoQ. The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0. The preclinical efficacy of the two-drug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts. RESULTS: Erlotinib elevated Δψm in PDAC cells, facilitating tumor cell uptake and mitochondrial enrichment of Δψm-sensitive agents. MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses, while erlotinib pretreatment potentiated low doses of MitoQ. SynergyFinder suggested that these drugs synergistically induced tumor cell lethality. Consistent with in vitro data, erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent. CONCLUSION: Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

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.

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.

Mutations of GEMIN5 are associated with coenzyme Q10 deficiency: long-term follow-up after treatment.

GEMIN5 exerts key biological functions regulating pre-mRNAs intron removal to generate mature mRNAs. A series of patients were reported harboring mutations in GEMIN5. No treatments are currently available for this disease. We treated two of these patients with oral Coenzyme Q10 (CoQ10), which resulted in neurological improvements, although MRI abnormalities remained. Whole Exome Sequencing demonstrated compound heterozygosity at the GEMIN5 gene in both cases: Case one: p.Lys742* and p.Arg1016Cys; Case two: p.Arg1016Cys and p.Ser411Hisfs*6. Functional studies in fibroblasts revealed a decrease in CoQ10 biosynthesis compared to controls. Supplementation with exogenous CoQ10 restored it to control intracellular CoQ10 levels. Mitochondrial function was compromised, as indicated by the decrease in oxygen consumption, restored by CoQ10 supplementation. Transcriptomic analysis of GEMIN5 patients compared with controls showed general repression of genes involved in CoQ10 biosynthesis. In the rigor mortis defective flies, CoQ10 levels were decreased, and CoQ10 supplementation led to an improvement in the adult climbing assay performance, a reduction in the number of motionless flies, and partial restoration of survival. Overall, we report the association between GEMIN5 dysfunction and CoQ10 deficiency for the first time. This association opens the possibility of oral CoQ10 therapy, which is safe and has no observed side effects after long-term therapy.

Coenzyme Q10 supplementation in rheumatic diseases: A systematic review.

Coenzyme Q10 (CoQ10) is a potent antioxidant and anti-inflammatory substance used to treat some rheumatic diseases. Our objective was to review the use of CoQ10 in rheumatic diseases. PubMed/Medline, Embase, Scopus, and Web of Science databases were searched for articles on CoQ10 and rheumatic diseases between 1966 and April 2023. Twenty articles were found, including 483 patients. The investigated conditions were Fibromyalgia (FM) with 15 studies, Rheumatoid Arthritis (RA) with 3 studies, and Antiphospholipid Syndrome (APS) with 2 studies. After CoQ10 supplementation, RA patients observed improvements in disease activity index, inflammatory biomarkers (erythrocyte sedimentation rate), cytokine levels, and a decrease in malondialdehyde. In APS, CoQ10 improved endothelial function and decreased prothrombotic and proinflammatory mediators. Regarding FM, in most of the studies, the patients observed improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire (FIQ). The drug was well tolerated, with reports of minor side effects in two studies. CoQ10 supplementation seems to be efficacious as a complementary treatment for RA and FM. Upcoming studies with larger samples and including other rheumatic diseases are welcome.

Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy.

Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non-responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers idebenone reduction. In its oxidized form, idebenone inhibits complex I, decreasing respiratory function in cells. By retrospectively analyzing a large cohort of idebenone-treated LHON patients, classified by their response to therapy, we show that patients with homozygous or compound heterozygous NQO1 variants have the poorest therapy response, particularly if carrying the m.3460G>A/MT-ND1 LHON mutation. These results suggest consideration of patient NQO1 genotype and mitochondrial DNA mutation in the context of idebenone therapy.

Ameliorating impact of coenzyme Q10 on the profile of adipokines, cardiomyopathy, and hematological markers correlated with the glucotoxicity sequelae in diabetic rats.

BACKGROUND: In diabetes, high blood glucose induces glucotoxicity, resulting in the further damage of pancreatic beta-cells and then precipitating diabetic complications. This study was aimed to investigate the relationship between glucotoxicity with the level of adipokines, diabetic cardiomyopathy, and hematological markers. Moreover, the study examined the potential modulatory effect of coenzyme Q10 (CoQ10) on the aforementioned markers associated with the sequelae of diabetes mellitus. MATERIAL AND METHODS: Twenty-four male rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 16) or to remain uninduced (n = 8). The hyperglycemic status was induced in fasting rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer (pH 4.5). Three days after STZ injection, rats were divided into three groups; Normal control group (A), Diabetic control group (B), and CoQ10- treated diabetic group (C). The group (C) was fed with the basal diet supplemented with 5 g of CoQ10 per kilogram of diet for three weeks after the diabetes induction. After 21 days, the blood and serum samples were taken to conduct biochemical analyses. Blood glucose was determined by Blood Glucose Monitoring System. Adipokines or cytokines were evaluated by ELISA from a serum sample. Cardiac myopathy biomarkers were estimated by UP-Converting Phosphor Immunoassay Analyzer, and hematological parameters were measured by automatic hematology analyzer. RESULTS: In hyperglycemic rats, the level of fasting blood glucose, and serum level of resistin, omentin, TNF-α, and cardiomyopathy biomarkers significantly increased (P < 0.05). The treatment with CoQ10 significantly decreased the profile of adipokines and cardiomyopathy markers (cardiac enzymes and LPPLA2) in diabetic rats and also reduced glucose levels (P < 0.05). Lymphocyte percentages significantly decreased while significant increases were observed in granulocytes and MID percentages in hyperglycemic rats. CONCLUSION: Diabetic rats had higher serum levels of adipokines and cardiomyopathy markers. Among the hematological markers, GRA% and MID% increased while LYM% decreased. The profile of adipokines and cardiomyopathy markers improved when CoQ10 was supplemented. The study suggests that CoQ10 may have a beneficial effect on improving diabetic complications.

Coenzyme Q10 attenuates neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

BACKGROUND: Chronic use of tramadol can cause neurotoxic effects and subsequently cause neurodegeneration in the cerebellum. The main damage mechanisms identified are oxidative stress and inflammation. Currently, we investigated the effects of coenzyme Q10 (CoQ10) in attenuates of neurodegeneration in the cerebellum induced by chronic exposure to tramadol. MATERIAL AND METHODS: Seventy-two male mature albino rats were allocated into four equal groups, including; non-treated group, CoQ10 group (which received CoQ10 at 200 mg/kg/day orally for three weeks), tramadol group (which received tramadol hydrochloride at 50 mg/kg/day orally for three weeks), and tramadol+CoQ10 group (which received tramadol and CoQ10 at the same doses as the previous groups). Tissue samples were obtained for stereological, immunohistochemical, biochemical, and molecular evaluations. Also, functional tests were performed to evaluate behavioral properties. RESULTS: We found a significant increase in stereological parameters, antioxidant factors (catalase, glutathione, and superoxide dismutase), and behavioral function scores in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). In addition, malondialdehyde levels, the density of apoptotic cells, as well as the expression of pro-inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6) and autophagy (lysosome-associated membrane protein 2, autophagy-related 5, beclin 1, and autophagy-related 12) genes were considerably reduced in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). CONCLUSION: We conclude that the administration of CoQ10 has neuroprotective effects in the cerebellum of rats that have chronic exposure to tramadol.