Traumatic Brain Injury Alters Cerebral Concentrations and Redox States of Coenzymes Q9 and Q10 in the Rat

Abstract

To date, there is no information on the effect of TBI on the changes in brain CoQ levels and possible variations in its redox state. In this study, we induced graded TBIs (mild TBI, mTBI and severe TBI, sTBI) in male rats, using the weight-drop closed-head impact acceleration model of trauma. At 7 days post-injury, CoQ9, CoQ10 and α-tocopherol were measured by HPLC in brain extracts of the injured rats, as well as in those of a group of control sham-operated rats. In the controls, about the 69% of total CoQ was in the form of CoQ9 and the oxidized/reduced ratios of CoQ9 and CoQ10 were, respectively, 1.05 ± 0.07 and 1.42 ± 0.17. No significant changes in these values were observed in rats experiencing mTBI. Conversely, in the brains of sTBI-injured animals, an increase in reduced and a decrease in oxidized CoQ9 produced an oxidized/reduced ratio of 0.81 ± 0.1 (p < 0.001 compared with both controls and mTBI). A concomitant decrease in both reduced and oxidized CoQ10 generated a corresponding oxidized/reduced ratio of 1.38 ± 0.23 (p < 0.001 compared with both controls and mTBI). An overall decrease in the concentration of the total CoQ pool was also found in sTBI-injured rats (p < 0.001 compared with both controls and mTBI). Concerning α-tocopherol, whilst no differences compared with the controls were found in mTBI animals, a significant decrease was observed in rats experiencing sTBI (p < 0.01 compared with both controls and mTBI). Besides suggesting potentially different functions and intracellular distributions of CoQ9 and CoQ10 in rat brain mitochondria, these results demonstrate, for the first time to the best of knowledge, that sTBI alters the levels and redox states of CoQ9 and CoQ10, thus adding a new explanation to the mitochondrial impairment affecting ETC, OXPHOS, energy supply and antioxidant defenses following sTBI.

Sex-specific antioxidant biomarker depletion in patients with a history of mild traumatic brain injury

“…When these processes persist, the endogenous antioxidant system becomes depleted as brain endogenous antioxidants like superoxide dismutase (SOD) or glutathione (GSH) work to remove and neutralize ROS/RNS. Only a few studies have explored antioxidant depletion following TBI [ 26 , 27 , 43 , 44 ]. However, to our knowledge, no studies to date have reported extensive and chronic antioxidant depletion in human subjects in response to mTBI.…”

“…A few novel studies (2020-present) have begun to explore antioxidant levels following TBI. In a rat model of TBI, coenzyme-q9, coenzyme-q10, and α-tocopherol were found to be significantly reduced in brain tissue one-week post-severe TBI, although no differences were observed following mTBI [ 26 ]. Another study measured total antioxidant capacity in serum in humans one-week post-severe TBI and reported it may be indicative of survival outcomes [ 27 ].…”

Bilirubin Concentration in Follicular Fluid Is Increased in Infertile Females, Correlates with Decreased Antioxidant Levels and Increased Nitric Oxide Metabolites, and Negatively Affects Outcome Measures of In Vitro Fertilization

“…FF supernatants (500 µL) were light-protected, deproteinized by the addition of 1 mL of HPLC-grade acetonitrile, vortexed for 60 s and placed in a water bath for 1 h at 37 • C. As previously shown, this procedure allows the quantitative recovery of fat-soluble compounds in biological samples [49][50][51][52]. Protein-free FF were obtained by centrifugation at 20,690× g for 15 min at 4 • C and then saved at −80 • C until the HPLC analysis of fat-soluble compounds, including free and bound bilirubin.…”