Quinolinic Acid Impairs Redox Homeostasis, Bioenergetic, and Cell Signaling in Rat Striatum Slices: Prevention by Coenzyme Q10

Quinolinic acid (QUIN) is an important agonist of NMDA receptors that are found at high levels in cases of brain injury and neuroinflammation. Therefore, it is necessary to investigate neuroprotection strategies capable of neutralizing the effects of the QUIN on the brain. Coenzyme Q(10) (CoQ(10)) is a provitamin that has an important antioxidant and anti-inflammatory action. This work aims to evaluate the possible neuroprotective effect of CoQ(10) against the toxicity caused by QUIN. Striatal slices from 30-day-old Wistar rats were preincubated with CoQ(10) 25-100 mu M for 15 min; then, QUIN 100 mu M was added to the incubation medium for 30 min. A dose-response curve was used to select the CoQ(10) concentration to be used in the study. Results showed that QUIN caused changes in the production of ROS, nitrite levels, activities of antioxidant enzymes, glutathione content, and damage to proteins and lipids. CoQ(10) was able to prevent the effects caused by QUIN, totally or partially, except for damage to proteins. QUIN also altered the activities of electron transport chain complexes and ATP levels, and CoQ(10) prevented totally and partially these effects, respectively. CoQ(10) prevented the increase in acetylcholinesterase activity, but not the decrease in the activity of Na+,K+-ATPase caused by QUIN. We also observed that QUIN caused changes in the total ERK and phospho-Akt content, and these effects were partially prevented by CoQ(10). These findings suggest that CoQ(10) may be a promising therapeutic alternative for neuroprotection against QUIN neurotoxicity.

Automated summary

Quinolinic acid (QUIN) is an important agonist of NMDA receptors that are found at high levels in cases of brain injury and neuroinflammation. This study found that coenzyme Q(10) (CoQ(10)) can mitigate the toxicity caused by QUIN in the brain, including reducing the generation of reactive oxygen species, alleviating oxidative stress, preserving the activity of antioxidant enzymes, maintaining glutathione levels, reducing protein and lipid damage, and preventing alterations in electron transport chain complex activity and ATP levels. CoQ(10) may be a promising therapeutic alternative for neuroprotection against QUIN neurotoxicity.