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3D reconstruction of mitochondrial cristae in the ONH astrocytes. Oxidative stress dilated cristae that were prevented by CoQ10/H2O2 treatment. Electron tomography generated high-resolution, 3D reconstructions of control, H2O2-exposed and CoQ10/H2O2-treated mitochondria. Slices (1.4-nm thick) through the middle of electron microscopy tomographic volumes of mitochondria are shown on the left. Surface-rendered volumes of the segmented mitochondria provide information concerning shape and cristae architecture. The outer mitochondrial membrane is shown in blue (made translucent to better visualize the cristae) and cristae are in various colors. The long control mitochondrion has 46 cristae, the H2O2-exposed has 47 cristae distributed in the four mitochondria that are lined up and the CoQ10/H2O2-treated mitochondrion has 27 cristae. The mean of cristae widths is 50% greater in the H2O2-exposed mitochondria compared with the control and CoQ10 pretreatment samples. Scale bar, 250 nm (all panels). Values are mean ±S.E.M. *Significant at P<0.05 and ***Significant at P<0.001 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. Representative graphs show the measurement of cristae widths and abundance in the mitochondria. CoQ10, coenzyme Q10; H2O2, hydrogen peroxide
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Oxidative stress contributes to dysfunction of glial cells in the optic nerve head (ONH). However, the biological basis of the precise functional role of mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain and a potent antioxidant, acts by scavenging reactive oxygen s...
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Mitochondria are the primary source for energy generation in the cell, which manifests itself in the form of the adenosine triphosphate (ATP). Nicotinamide dinucleotide (NADH) molecules are the first to enter the so-called electron transport chain or ETC of the mitochondria. The ETC represents a chain of reducing agents organized into four major pr...
Citations
... Furthermore, in the previous study, we reported that methylglyoxal, a precursor of AGEs, reduces exercise-induced mitochondrial adaptations in mouse skeletal muscle (Egawa et al., 2022). In this regard, one study showed that 1 h of H 2 O 2 stimulation significantly increased the expression of OXPHOS proteins, possibly because oxidative stress-mediated reactive oxygen species (ROS) alter OXPHOS function (Noh et al., 2013). Furthermore, AMPK activation induced by ROS-mediated ATP depletion in skeletal muscle cells promotes PGC-1α transcription (Barbieri & Sestili, 2012). ...
Advanced glycation end products (AGEs) have been implicated in several skeletal muscle dysfunctions. However, whether the adverse effects of AGEs on skeletal muscle are because of their direct action on the skeletal muscle tissue is unclear. Therefore, this study aimed to investigate the direct and acute effects of AGEs on skeletal muscle using an isolated mouse skeletal muscle to eliminate several confounders derived from other organs. The results showed that the incubation of isolated mouse skeletal muscle with AGEs (1 mg/mL) for 2–6 h suppressed protein synthesis and the mechanistic target of rapamycin signaling pathway. Furthermore, AGEs showed potential inhibitory effects on protein degradation pathways, including autophagy and the ubiquitin–proteasome system. Additionally, AGEs stimulated endoplasmic reticulum (ER) stress by modulating the activating transcription factor 6, PKR‐like ER kinase, C/EBP homologous protein, and altered inflammatory cytokine expression. AGEs also stimulated receptor for AGEs (RAGE)‐associated signaling molecules, including mitogen‐activated protein kinases. These findings suggest that AGEs have direct and acute effect on skeletal muscle and disturb proteostasis by modulating intracellular pathways such as RAGE signaling, protein synthesis, proteolysis, ER stress, and inflammatory cytokines.
... Glaucoma is the leading cause of irreversible blindness and affects more than 60 million people worldwide, of which nearly 10% of cases are estimated to result in blindness (Quigley and Broman, 2006;Ulhaq, 2020a;. Although lowering intraocular pressure (IOP) can alleviate glacoma symptoms, it does not necessarily impede the progression of optic nerve head (ONH) and retinal ganglion cell (RGC) degeneration (Edwards et al., 2020;Noh et al., 2013;Ulhaq et al., 2021aUlhaq et al., , 2022. The exact factors contributing to RGC and axon degeneration in glaucoma are still not fully understood. ...
... In such conditions, the cell relies on its antioxidant defense system to neutralize and regulate the levels of ROS (Fu et al., 2021). Therefore, impairment in the mitochondrial oxidative phosphorylation (OXPHOS) pathway results in ROS overproduction, which in turn leads to oxidative stress and the development of multiple retinal disorders, including glaucoma (Noh et al., 2013). Indeed, robust evidence indicates a significant increase in oxidative DNA damage within the trabecular meshwork (TM) of glaucomatous individuals (Saccà et al., 2005;Wu et al., 2022). ...
Glaucoma is one of the leading causes of visual impairment and blindness worldwide, and is characterized by the progressive damage of retinal ganglion cells (RGCs) and the atrophy of the optic nerve head (ONH). The exact cause of RGC loss and optic nerve damage in glaucoma is not fully understood. The high energy demands of these cells imply a higher sensitivity to mitochondrial defects. Moreover, it has been postulated that the optic nerve is vulnerable towards damage from oxidative stress and mitochondrial dysfunction. To investigate this further, we conducted a pooled analysis of mitochondrial variants related to energy production, specifically focusing on oxidative phosphorylation (OXPHOS) and fatty acid β-oxidation (FAO). Our findings revealed that patients carrying non-synonymous (NS) mitochondrial DNA (mtDNA) variants within the OXPHOS complexes had an almost twofold increased risk of developing glaucoma. Regarding FAO, our results demonstrated that longer-chain acylcarnitines (AC) tended to decrease, while shorter-chain AC tended to increase in patients with glau-coma. Furthermore, we observed that the knocking down cpt1a (a key rate-limiting enzyme involved in FAO) in zebrafish induced a degenerative process in the optic nerve and RGC, which resembled the characteristics observed in glaucoma. In conclusion, our study provides evidence that genes encoding mitochondrial proteins involved in energy metabolisms, such as OXPHOS and FAO, are associated with glaucoma. These findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and may offer potential targets for therapeutic interventions in the future.
... BMSCs were treated with H 2 O 2 (Sigma-Aldrich, USA) at 100 μM for 2 h to induce the intracellular oxidative stress [28,52,53], followed by treatment with Garcinol (2.5, 5, 7.5, 10 μM) for 48 h. ...
There are multiple published data showing that excessive oxidative stress contributes to bone loss and even bone tissue damage, and it is also correlated with the pathophysiology of bone degenerative diseases, including osteoporosis (OP). Garcinol, a polyisoprenylated benzophenone derivative, has been recently established as an anti-oxidant agent. However, it remains elusive whether Garcinol protects bone marrow mesenchymal stem cells (BMSCs) and bone tissue from oxidative stress-induced damage. Here, we explored the potential effects of Garcinol supplementation in ameliorating oxidative stimulation-induced dysfunction of BMSCs and bone loss in osteoporotic mice. In this study, we verified that Garcinol exerted potent protective functions in the hydrogen peroxide (H 2 O 2 )-induced excessive oxidative stress and dysfunction of BMSCs. Besides, Garcinol was also identified to improve the reduced bone mass and abnormal lineage commitment of BMSCs in the condition of OP by suppressing the oxidative stimulation. Subsequent analysis revealed that nuclear factor erythroid 2-related factor 2 (NRF2) might be a key regulator in the sheltering effects of Garcinol on the H 2 O 2 -regulated oxidative stress, and the protective functions of Garcinol was mediated by NRF2-antioxidant signaling. Collectively, Garcinol prevented oxidative stress-related BMSC damage and bone loss through the NRF2-antioxidant signaling, which suggested the promising therapeutic values of Garcinol in the treatment of oxidative stress-related bone loss. Therefore, Garcinol might contribute to treating OP.
... Pre-administration of CoQ 10 had some positive effects on aged IR hearts via improving mitochondrial membrane potential and decreasing ROS generation. Consistent with our results, previous studies have shown that CoQ 10 treatment reduces the deleterious effects of IR injury on mitochondria by improving the bioenergetic status of mitochondria and preventing mitochondrial oxidative damage (Noh et al., 2013, Lu et al., 2017a. Liang et al. showed that CoQ 10 reduced infarct size and improved cardiac function in the rats subjected to IR injury through balancing oxidants and antioxidants, increasing autophagy, and decreasing myocardial apoptosis (Liang et al., 2017). ...
Background:
Ischemic heart diseases (IHD) are among the major causes of mortality in elderly population. Although timely reperfusion is a commen treatment for IHD, it also causes additional damage to the ischemic myocardium known as ischemia/reperfusion (IR) injury. Considering the importance of preventing reperfusion injuries, we aimed to examine the combination effect of mitochondrial transplantation and coenzyme Q10 (CoQ10) in myocardial IR injury of aged rats.
Methods:
Seventy-two aged male Wistar rats were randomly divided into 6 groups: Sham, IR, CoQ10, mitochondrial transplantation (MT), combination therapy (MT+CoQ10), and vehicle. Myocardial IR injury was established by occlusion of the left anterior descending coronary artery and re-opening. Young male Wistar rats were used as mitochondria donors. Isolated mitochondria were injected intraventricularly (500µl of the respiration buffer containing 6×10⁶±5×10⁵ mitochondria) in MT receiving groups at the onset of reperfusion. CoQ10 (10mg/kg/day) was injected intraperitoneally for two weeks before IR induction. Twenty-four hours after reperfusion, hemodynamic parameters, myocardial infarct size (IS), LDH level, and cardiac mitochondrial function (mitochondrial ROS generation and membrane potential) were measured.
Result:
Combination of mitochondrial transplantation and CoQ10 improved hemodynamic index changes and reduced IS and LDH level (P<.05). It also decreased mitochondrial ROS generation and increased membrane potential (P<.05).
showed a significant cardioprotective effect. Combination therapy showed greater cardioprotective effects than single treatments.
Conclusion:
This study revealed that mitochondrial transplantation and CoQ10 combination treatment can be considered as a promising cardioprotective strategy to reduce myocardial IR injury in aging, in part by restoring mitochondrial function.
... In ovo CoQ10 injection could depress fatty acid oxidation and prevent the production of free radicals that seriously harm the cellular membranes of developing embryos during the incubation phase. (Noh et al.,2013), as well as enhance lipid utilization for energy production to maximize hatchability (Gopi et al., 2015). Therefore, improving hatchability percentage in this study could relate to in ovo CoQ10 injection that improved antioxidant status of hatching eggs or prevent oxidation stresses against. ...
ABSTRACT: This research was done to find out the effect of in ovo injection of
Coenzyme Q10 (CoQ10) at various incubation ages on the physiological and immunity
performance of Mamora chickens. A total of 630 hatching eggs were divided into 7
equal treatments (90 eggs per each). The first group was as a negative control, the
second group was as a positive control (injected in air sac with 0.3 ml/egg of distilled
water at day 1 of incubation), the third and fourth groups were injected with 0.3 ml/egg
of distilled water contained 0.1 and 0.2 ml coenzyme Q10 / egg respectively at day1 of
incubation, the fifth group was as a second positive control (injected in air sac with 0.3
ml/egg of distilled water at day18), the six and seven groups were injected with 0.3
mL/egg solution of sterile distilled water contained 0.1 and 0.2 mL coenzyme Q10 /
egg, respectively at day18 of incubation, Hatched chicks of each treatment were reared
till 28 days of age. Results obtained could be summarized as follow: improving the
hatchability percentage and decreasing embryonic mortality by in ovo CoQ10 at the 1st
and the 18th day of incubation period as compared with negative control group. In ovo
injection with CoQ10 led to improve the subsequent growth traits after hatch within the
period of 1-28 day of age. Lymphocytes (L, %) was elevated, while heterophils (H, %)
was decreased for chicks hatched from eggs injected with 0.2 ml CoQ10 / egg at the 1st
day of incubation. All chicks produced from injected eggs with CoQ10 had higher
serum catalase enzyme value and lower liver enzymes (AST & ALT) compared with
those of negative or positive control. Therefore, in ovo CoQ10 (0.1 or 0.2 ml/egg)
injection improve hatchability, post-hatch chick development, and physiological
response of hatched Mamora.
... It is estimated that 57.5 million individuals worldwide are affected by primary openangle glaucoma (POAG), and this number will reach 111.8 million by 2040 [1]. Retinal ganglion cell (RGC) apoptosis is a hallmark of glaucoma, which has a multifactorial cause, and the mechanisms causing glaucomatous neurodegeneration are not fully understood [2][3][4]. Pathologically high intraocular pressure (IOP) is an important but not the only risk factor for glaucoma [2]. Clinical observation has revealed that some individuals still experience visual impairment even after their IOP has been brought under control with medication or surgery, and some people experience normal tension glaucoma [5]. ...
Purpose:
To investigate whether asiatic acid (AA) can improve the quantity and function of retinal ganglion cells (RGCs), as well as how AA regulates synaptic pathways in rat models with chronic glaucoma.
Methods:
In our study, a rat model of chronic glaucoma was prepared via the electrocoagulation of the episcleral veins. The numbers of surviving RGCs were counted via retrograde Fluorogold labeling, and a whole-cell patch clamp was used to clamp RGCs in normal retinal sections and in retinal sections 4 weeks after glaucoma induction.
Results:
Retrograde-Fluorogold-labeled RGC loss caused by persistent glaucoma was decreased by AA. Additionally, AA reduced the postsynaptic current produced by N-methyl-D-aspartate (NMDA) and diminished miniature glutamatergic excitatory neurotransmission to RGCs. On the other hand, AA increased miniature gamma-aminobutyric acid (GABA)-ergic inhibitory neurotransmission to RGCs and enhanced the GABA-induced postsynaptic current. The excitability of the RGC itself was also decreased by AA. RGCs in glaucomatous slices were less excitable because AA decreased their spontaneous action potential frequency and membrane potential, which led to a hyperpolarized condition.
Conclusions:
AA directly protected RGCs in a chronic glaucoma rat model by lowering their hyperexcitability. To enhance RGCs' survival and function in glaucoma, AA may be a viable therapeutic drug.
... However, whether similar protection can be conferred to mitochondrial DNA has yet to be investigated. In our current study, we created a formula containing 10 different ingredients with antioxidant properties, which have been shown to be beneficial against radiationinduced damage by reducing lethality [21] or attenuating markers of DNA and cellular damage [18][19][20], including quercetin [22,23], astaxanthin [24], zeaxanthin [25], vitamin C [26], vitamin B 12 [27], selenium [28], folate [29], CoQ10 [30,31], α-lipoic acid [32], and vitamin E [33]. Importantly, we specifically chose to include CoQ10, vitamin E, and α-lipoic acid, as they were the main components of a multi-ingredient supplement that we have shown lowered lactate and oxidative stress markers in patients with primary mitochondrial myopathy [34]. ...
Radiation exposure is an undeniable health threat encountered in various occupations and procedures. High energy waves in ionizing radiation cause DNA damage and induce reactive oxygen species (ROS) production, which further exacerbate DNA, protein, and lipid damage, increasing risk of mutations. Although endogenous antioxidants such as superoxide dismutase have evolved to upregulate and neutralize ROS, exogenous dietary antioxidants also have the potential to combat ionizing radiation (IR)-induced ROS production. We evaluated a cocktail of ingredients (AOX) purported to have antioxidant and mitochondrial protective properties on the acute effects of IR. We show that IR stimulates DNA damage through phosphorylation of DNA repair proteins in the heart, brain, and liver of mice. AOX showed partial protection in brain and liver, through a lack of significant activation in given repair proteins. In addition, AOX attenuated the IR-induced increase in NF-kβ mRNA and protein expression in brain and liver. Lastly, cytochrome c oxidase complex transcripts were significantly higher in heart and brain following radiation, which was also diminished by prior ingestion of AOX. Together, our findings suggest that a multi-ingredient AOX supplement may attenuate the IR-induced cellular damage response and represents a feasible and cost-effective preventative supplement for at-risk populations of radiation exposure.
... It significantly decreased two well-known processes that activate during oxidative stress: the Superoxide dismutase 2 (SOD2) and Heme oxygenase-1 (HO-1) protein expression. Hence, CoQ10 was able to prevent mitochondrial damage and the decline of ATP production (34). ...
... In this condition CoQ10 showed partial preservation of mitochondrial morphology, increased mitochondrial numbers and mitochondrial volume density. This is possibly due to CoQ10 ability to promote mitofilin protein expression, providing protection to the mitochondria and ultimately OXPHOS capacity against oxidative stress (34). ...
Glaucoma is the leading cause of irreversible blindness worldwide. Several risk factors have been involved in the pathogenesis of the disease. By now, the main treatable risk factor is elevated intraocular pressure. Nevertheless, some patients, whose intraocular pressure is considered in the target level, still experience a progression of the disease. Glaucoma is a form of multifactorial ocular neurodegeneration with complex etiology, pathogenesis, and pathology. New evidence strongly suggests brain involvement in all aspects of this disease. This hypothesis and the need to prevent glaucomatous progression led to a growing interest in the pharmacological research of new neuroprotective, non-IOP-lowering, agents. The aim of this paper is to report evidence of the usefulness of Coenzyme Q10 and Citicoline, eventually combined, in the prevention of glaucomatous neurodegeneration.
... CoQ 10 plays an essential role in mitochondrial respiratory chain, lipid peroxidation and oxidative stress [99,100]. One of the most important mechanisms through which CoQ 10 exert its antioxidant properties is the suppression of activity of enzymes involved in the production of ROS [101,102]. In diabetes, several studies have shown that CoQ 10 levels are decreased in association with excessive production of ROS [103,104]. ...
Lipid peroxidation, including its prominent byproducts such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), has long been linked with worsened metabolic health in patients with type 2 diabetes (T2D). In fact, patients with T2D already display increased levels of lipids in circulation, including low-density lipoprotein-cholesterol and triglycerides, which are easily attacked by reactive oxygen molecules to give rise to lipid peroxidation. This process severely depletes intracellular antioxidants to cause excess generation of oxidative stress. This consequence mainly drives poor glycemic control and metabolic complications that are implicated in the development of cardiovascular disease. The current review explores the pathological relevance of elevated lipid peroxidation products in T2D, especially highlighting their potential role as biomarkers and therapeutic targets in disease severity. In addition, we briefly explain the implication of some prominent antioxidant enzymes/factors involved in the blockade of lipid peroxidation, including termination reactions that involve the effect of antioxidants, such as catalase, coenzyme Q10, glutathione peroxidase, and superoxide dismutase, as well as vitamins C and E.
... The average concentration of CoQ10 in the blood ranges between 0.50 and 1.91 µmol/L [336,337]. Concentrations below these are associated with aging and diseases such as hypertension, coronary artery disease, cardiovascular disease, diabetes mellitus, and cancer [333,338], while CoQ10 supplementation shows decreased oxidative stress and the increased activity of antioxidant enzymes [339], resulting in attenuation of the severity of different diseases and conditions [333,338,340]. ...
Oxidative stress (OS) has greatly interested the research community in understanding
damaging processes occurring in cells. OS is triggered by an imbalance between reactive oxygen species (ROS) production and their elimination by the antioxidant system; however, ROS function as second messengers under physiological conditions. ROS are produced from endogenous and exogenous sources. Endogenous sources involve mitochondria, nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), oxidases (NOXs), endoplasmic reticulum (ER), xanthine oxidases (XO), endothelial nitric oxide synthase (eNOs), and others. In contrast, exogenous ROS might be generated through ultraviolet (UV) light, ionizing radiation (IR), contaminants, and heavy metals, among others. It can damage DNA, lipids, and proteins if OS is not controlled. To avoid oxidative
damage, antioxidant systems are activated. In the present review, we focus on the basic concepts of OS, highlighting the production of reactive oxygen and nitrogen species (RONS) derived from internal and external sources and the last elimination. Moreover, we include the cellular antioxidant system regulation and their ability to decrease OS. External antioxidants are also proposed as alternatives to ameliorate OS. Finally, we review diseases involving OS and their mechanisms.
