ubiquinone and Spinal-Cord-Injuries

Spinal cord injury (SCI) has always been considered to be a devastating problem that results in catastrophic dysfunction, high disability rate, low mortality rate, and huge cost for the patient. Stem cell-based therapy, especially using bone marrow mesenchymal stem cells (BMSCs), is a promising strategy for the treatment of SCI. However, SCI results in low rates of cell survival and a poor microenvironment, which limits the therapeutic efficiency of BMSC transplantation. Coenzyme Q10 (CoQ10) is known as a powerful antioxidant, which inhibits lipid peroxidation and scavenges free radicals, and its combined effect with BMSC transplantation has been shown to have a powerful impact on protecting the vitality of cells, as well as antioxidant and antiapoptotic compounds in SCI. Therefore, we aimed to evaluate whether CoQ10 could decrease oxidative stress against the apoptosis of BMSCs

Topics: Animals; Apoptosis; Bone Marrow Cells; Disease Models, Animal; Hydrogen Peroxide; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord Injuries; Ubiquinone

The roles of the immune response and apoptosis as potential mediators of secondary damage in spinal cord injury (SCI) are being investigated. Research is also being done to determine the effects of female gonadal steroids, which decrease during menopause, and antioxidants, such as coenzyme Q10 (CoQ10) on SCI. We hypothesized that in the absence of female gonadal steroids, which provide protection following an SCI, CoQ10 could modulate the expression of cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-10, besides aquaporin-4 (AQP4) water channels in the CNS, which participate in neuroinflammation, as well as the Bax and Bcl2 proteins that are involved in apoptosis at the site of injury. The spinal cord was compressed at the level of the T10 vertebrae and rats were treated by 10 mg/kg/day CoQ10 for 3 weeks after surgery. The TNF-α and IL-10 expressions were studied using an ELISA. Western blot was used to investigate the Bax/Bcl-2 ratio, AQP4. The level of TNF-α significantly decreased following the administration of CoQ10 compared with the level of IL-10. When the treatment group was compared with the OVX-SCI group, the ratio of Bax/Bcl2 significantly decreased in the groups (P < 0.01). Based on our findings, CoQ10 could be used to compensate for the absence of the neuroprotection effects provided by female gonadal steroids via reducing the inappropriate effects of the two main pathways of secondary damage in SCI apoptosis.

Topics: Animals; Aquaporins; Female; Gonadal Steroid Hormones; Interleukin-10; Lumbar Vertebrae; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries; Tumor Necrosis Factor-alpha; Ubiquinone

Spinal cord injury (SCI)‑induced osteoporosis may cause mild trauma to bone and increase the risk of bone fracture. The present study aimed to investigate the efficacy of coenzyme Q (CoQ10) on SCI‑induced osteoporosis in rats. SCI was induced by surgical transection of the cord at the T10‑12 level. Animals were treated with CoQ10 (10 mg/kg; intragastrically) daily from 12 h after the surgery and over 10 subsequent days. At the end of the experimental period, blood was collected from the animals and femurs and tibiae were removed for evaluation using biochemical assays. Treatment with CoQ10 prevented SCI‑induced bone loss by rescuing the decreased levels of bone mineral density and bone mineral content observed in the SCI rats. Furthermore, CoQ10 administration reduced bone malondialdehyde levels with a concomitant increase in superoxide dismutase levels, thus alleviating SCI‑induced oxidative injury. In addition, serum inflammatory cytokine levels were markedly increased in rats post‑SCI, which was attenuated by treatment with CoQ10. Finally, the osteoclast‑specific genes receptor activator of nuclear factor kappa‑B ligand and cathepsin K were significantly upregulated and the osteoblast‑specific gene core‑binding factor alpha 1 in the femur was downregulated following SCI, which was effectively restored following treatment with CoQ10. The results suggested that CoQ10 treatment may be effective in attenuating SCI‑induced osteoporosis.

Topics: Animals; Bone Density Conservation Agents; Drug Evaluation, Preclinical; Femur; Gene Expression; Interleukin-6; Male; Osteoblasts; Osteoclasts; Osteoporosis; Oxidative Stress; Rats, Sprague-Dawley; Spinal Cord Injuries; Tibia; Tumor Necrosis Factor-alpha; Ubiquinone

The mitochondrion participates in caspase-independent or caspase-dependent apoptotic pathways through the release of apoptosis-inducing factor or cytochrome c. Whether both mitochondrial apoptotic cascades are triggered in the injured spinal cord remains unknown. Here, we demonstrated that neurons, astrocytes and microglia in spinal segments proximal to a complete spinal cord transection underwent two phases of apoptotic cell death. The early phase of high-molecular weight (HMW) DNA fragmentation was associated with nuclear translocation of apoptosis-inducing factor, reduction in mitochondrial respiratory chain enzyme activity and decrease in cellular ATP concentration. The delayed phase of low-molecular weight (LMW) DNA fragmentation was accompanied by cytosolic release of cytochrome c, activation of caspases 9 and 3, and resumption of mitochondrial respiratory functions and ATP contents. Microinfusion of coenzyme Q(10), an electron carrier in mitochondrial respiratory chain, into the epicenter of the transected spinal cord attenuated both phases of induced apoptosis, and reversed the elicited mitochondrial dysfunction, bioenergetic failure, and activation of apoptosis-inducing factor, cytochrome c, or caspases 9 and 3. We conclude that mitochondrial dysfunction after spinal cord transection represents the initiating cellular events that trigger the sequential activation of apoptosis-inducing factor-dependent and caspase-dependent signaling cascades, leading to apoptotic cell death in the injured spinal cord.

Topics: Adenosine Triphosphate; Animals; Apoptosis; Apoptosis Inducing Factor; Caspase 3; Caspase 9; Coenzymes; Cytochromes c; DNA Fragmentation; Electron Transport; Electron Transport Complex IV; Male; Mitochondria; NADH Dehydrogenase; Protein Transport; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms; Spinal Cord; Spinal Cord Injuries; Ubiquinone

In this study, we aimed to compare the efficacy of methylprednisolone, coenzyme Q(10) and combined methylprednisolone and coenzyme Q(10) treatments on experimental spinal cord injury.. Thirty-two male Sprague-Dawley rats (200-250 g) were divided into four groups. Spinal cord injury (SCI) was performed by placement of an aneurysm clip, extradurally at the level of T4-5. After the trauma, group K (control group) received soybean oil, group M (methylprednisolone group) received 30 mg.kg-1 methylprednisolone and 5.4 mg.kg.hour-1 maintenance dose of methylprednisolone, group Q (coenzyme Q(10) group) received 10 mg.kg-1 coenzyme Q(10), group MQ (methylprednisolone and coenzyme Q(10) group) received 30 mg.kg-1 methylprednisolone and 5.4 mg.kg.hour-1 maintenance dose of methylprednisolone and 10 mg.kg-1 coenzyme Q(10) intraperitoneally. Twenty-four hours after the trauma spinal cord samples of the rats were obtained and tissue samples had been harvested for both biochemical and histopathological evaluation.. In histopathological examination, the edema pattern was significantly more severe in group K than the group M, group Q and group MQ (p<0.001). There was no statistically significant difference between group M, group Q and group MQ regarding edema and bleeding (p>0.05). Mean superoxide dismutase (SOD) scores were significantly low while comparing the group K with all remaining groups and the group MQ comparing with the group M (p<0.05). Mean malondialdehyde (MDA) scores were low in the group M, Q and MQ in comparison with the group K, but there was no statistically significant difference between all groups (p>0.05).. Methylprednisolone, coenzyme Q(10) and combined methylprednisolone and coenzyme Q(10) treatments were found to be effective as they decrease the edema and coenzyme Q(10) could be effective for prevention of secondary injury at experimental SCI.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Drug Therapy, Combination; Edema; Injections, Intraperitoneal; Injury Severity Score; Male; Methylprednisolone; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Superoxide Dismutase; Thoracic Vertebrae; Ubiquinone

Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to delayed tissue damage following traumatic spinal cord injury (SCI). Ubiquinols (reduced coenzyme Q), ascorbate (vitamin C), and alpha-tocopherol (vitamin E) are endogenous antioxidants; decreases in tissue levels of these compounds may, therefore, reflect ongoing oxidative reactions. In the present studies, alterations in tissue levels of ubiquinol-9 and -10, ascorbate, and alpha-tocopherol were examined after SCI of varying severity in the rat. Levels of alpha-tocopherol did not change significantly after injury. Ascorbate and ubiquinol levels were decreased after trauma. Changes in tissue levels of ubiquinol, but not ascorbate reflected the degree of trauma. Thus, ubiquinol levels may provide a useful marker of the oxidative component of the secondary injury response.

Topics: Animals; Antioxidants; Ascorbic Acid; Male; Rats; Rats, Inbred Strains; Spinal Cord Injuries; Ubiquinone; Vitamin E

Local tissue oxygen consumption, nicotinamide-adenine dinucleotide hydrogenase, coenzyme-Q and alpha-tocopherol were measured and the relationships between damage to the hydrogen electron transport system and free radical reactions were examined in a irreversible rat spinal cord injury model. Damage to the hydrogen electron transport system became apparent in the injured spinal cord segment earlier than expected. Oxygen consumption declined to 26% of the baseline level within five to 30 minutes after injury, by one hour, further declined by 21% and by two hours another 17% and by three to four hours by an additional 13%. This severe disturbance of oxygen metabolism was associated with a marked reduction of adenosine triphosphate. A reduction in coenzyme-Q by 50% was noted within 10 minutes after injury and might be at least partially responsible for these changes since a reduction of coenzyme-Q promotes the semiquinone (.coenzyme-Q) forming reaction and also produces the superoxide radical X O2-. While coenzyme-Q reacts with H+ ion, this superoxide radical X O2-, produce a state of scavenger wastage and hyperoxygenation of nicotinamide-adenine dinucleotide hydrogenase at two hours after injury. Lipid peroxigenation resulted from damage to the hydrogen electron transport system which created a state of energy metabolite disruption and cellular membrane damage and ultimately led to cellular autolysis.

Topics: Animals; Electron Transport; Energy Metabolism; Free Radicals; Hydrogen; Hydrogen-Ion Concentration; NAD; Oxygen Consumption; Rats; Spinal Cord; Spinal Cord Injuries; Ubiquinone; Vitamin E