Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

Abstract

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.

Antioxidant Therapies in Traumatic Brain Injury

“…Compared to trauma only, this treatment decreased MDA levels, vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia and axonal edema, and increased cerebral SOD [98]. In rats receiving TBI according to CCI, administration of CoQ 10 immediately after impact was found to significantly affect the cerebral expression of genes involved in mechanisms of bioenergetics and oxidative/nitrosative stress [99]. The same research group tested the effects of intra-arterial CoQ 10 infusion before or 30 min after TBI induced by CCI [100].…”

Effect of Ubiquinol on Glaucomatous Neurodegeneration and Oxidative Stress: Studies for Retinal Ganglion Cell Survival and/or Visual Function

“…CoQ 10 is a neurotherapeutic agent and potent antioxidant against mitochondrial dysfunction and oxidative stress in experimental glaucoma [ 8 , 10 , 13 , 22 , 23 , 24 , 25 , 26 ]. In the present study, we demonstrated that a diet supplementation with ubiquinol (1%) significantly enhanced RGC survival in a chronic mouse model of glaucoma, DBA/2J mice.…”

“…Recent evidence showed that ubiquinol, the reduced and active form of CoQ 10 , is protective in neuronal cells in several neurodegenerative diseases including Alzheimer’s disease, traumatic brain injury, and multiple system atrophy [ 10 , 11 , 12 , 13 ]. Importantly, emerging evidence from our group indicates that ubiquinol diet supplementation protects RGCs via modulating the BAX/BAD/BCL-xL-mediated apoptotic pathway in acute IOP elevation-induced ischemic retinal degeneration.…”

Ubiquinol promotes retinal ganglion cell survival and blocks the apoptotic pathway in ischemic retinal degeneration

“…Emerging evidence indicates that ubiquinol is neuroprotective in several neurodegenerative diseases including Alzheimer’s disease, multiple system atrophy, and traumatic brain injury [15–18]. In the current study, we tested whether a diet supplemented with ubiquinol promotes RGC survival, prevents glial activation, and blocks apoptotic cell death in the transient ischemic mouse retina.…”

“…CoQ 10 , an essential cofactor of the electron transport chain, acts by maintaining the mitochondrial membrane potential, supporting ATP synthesis and inhibiting reactive oxygen species generation for protecting neuronal cells in neurodegenerative diseases [12, 13]. As potent antioxidant and neurotherapeutic agents, CoQ 10 and ubiquinol, the reduced form of CoQ 10 , are attractive and useful supplements to test efficacy in retinal ischemia and glaucoma because the published evidence supports their effectiveness in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases [12, 14–18].…”