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 Q10 (CoQ10) is a provitamin that has an important antioxidant and anti-inflammatory action. This work aims to evaluate the possible neuroprotective effect of CoQ10 against the toxicity caused by QUIN. Striatal slices from 30-day-old Wistar rats were preincubated with CoQ10 25-100 µM for 15 min; then, QUIN 100 µM was added to the incubation medium for 30 min. A dose-response curve was used to select the CoQ10 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. CoQ10 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 CoQ10 prevented totally and partially these effects, respectively. CoQ10 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 CoQ10. These findings suggest that CoQ10 may be a promising therapeutic alternative for neuroprotection against QUIN neurotoxicity.

Bioactive compounds of parsley (Petroselinum crispum), chives (Allium schoenoprasum L) and their mixture (Brazilian cheiro-verde) as promising antioxidant and anti-cholesterol oxidation agents in a food system.

This study determined the bioactive composition and antioxidant potential of parsley, chives and their mixture (Brazilian cheiro-verde). Additionally, the effect of these herbs against cholesterol oxidation in grilled sardines (Sardinella brasiliensis) was also investigated. Ultra-high Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (UHPLC-ESI-MS) analyses revealed the presence of phenolic acids (caffeic, chlorogenic, and ferulic acids) and flavonoids (apigenin, kaempferol, catechin) in the herbs. Higher levels of phenolics (2.10 ± 0.02 mg GAE/g) and carotenoids (205.95 ± 0.17 µg/g) were determined in parsley extracts. Moreover, parsley also presented higher antioxidant capacity by DPPH (59.21 ± 0.07 %) and ORAC (109.94 ± 18.7 µM TE/g) than the other herbs. In vivo analyses demonstrated that the herbs' extracts decreased the damage on Saccharomyces cerevisiae cells exposed to H2O2, except the chives extract at 10 µg/mL. Higher levels of cholesterol oxidation products (COPs) were determined after grilling. The total COPs increased from 61.8 ± 0.7 (raw fish) to 139.7 ± 10.1 µg/g (control). However, the addition of herbs effectively reduced cholesterol oxides formation, this effect was more pronounced in fish containing 4% parsley and 4% cheiro-verde. Promising results were found for cheiro-verde; however, it did not present synergic antioxidant effects.

Folic acid supplementation during pregnancy alters behavior in male rat offspring: nitrative stress and neuroinflammatory implications.

Pregnancy diet can impact offspring's neurodevelopment, metabolism, redox homeostasis, and inflammatory status. In pregnancy, folate demand is increased due to the requirement for one-carbon transfer reactions. The present study was proposed to investigate the effect of folic acid supplementation throughout pregnancy on a battery of behavior tests (olfactory preference, motor activity, exploratory capacity, habituation, memory, anxiety- and depression-like behavior). Redox homeostasis and neuroinflammatory status in cerebral cortex were also investigated. After pregnancy confirmation, the pregnant rats were randomly divided into two groups, according to the diet: group 1, (control) standard diet (2 mg/kg diet of folic acid) and group 2, supplemented diet with 4 mg/kg diet of folic acid. Throughout the gestational period, the pregnant rats received experimental diets. Results show that the supplemented diet with 4 mg/kg diet of folic acid throughout pregnancy impaired memory and motricity of the offspring when compared with control (standard diet). It was also observed an increase in anxiety- and depression-like behavior in this group. Nitrite levels increased in cerebral cortex of the offspring, when compared to control group. In contrast, iNOS expression and immunocontent were not altered. Moreover, we identify an increase in TNF-α, IL-1ß, IL-6, IL-10, and MCP-1 gene expression in the cerebral cortex. In conclusion, our study showed that the supplemented diet with 4 mg/kg diet of folic acid throughout pregnancy may cause behavioral and biochemical changes in the male offspringGraphical abstract After pregnancy confirmation, the pregnant rats were randomly divided into two groups, according to the diet: group 1, (control) standard diet (2 mg/kg diet of folic acid) and group 2, supplemented diet with 4 mg/kg diet of folic acid. Throughout the gestational period, the pregnant rats received experimental diets. Results show that folic acid supplementation did not impair the mother-pup relationship. We showed that supplemented diet with 4 mg/kg diet of folic acid during pregnancy impairs memory and motricity of the offspring when compared with standard diet. It was also observed an increase in anxiety- and depression-like behavior in this group. Nitrative stress and neuroinflammation parameters were increased in the cerebral cortex of the offspring. ROS, reactive oxygen species.

Vitamin D partially reverses the increase in p-NF-κB/p65 immunocontent and interleukin-6 levels, but not in acetylcholinesterase activity in hippocampus of adult female ovariectomized rats.

The aim of this study was to verify the effects of ovariectomy (OVX) and/or vitamin D supplementation (VIT D) on inflammatory and cholinergic parameters in hippocampus, as well as on serum estradiol and VIT D levels of rats. Ninety-day-old female Wistar rats were randomly divided into four groups: SHAM, OVX, VIT D or OVX + VIT D. Thirty days after OVX, VIT D (500 IU/kg/day) was supplemented by gavage, for 30 days. Approximately 12 h after the last VIT D administration, rats were euthanized and hippocampus and serum were obtained for further analyses. Results showed that OVX rats presented a decrease in estradiol levels when compared to control (SHAM). There was an increase in VIT D levels in the groups submitted to VIT D supplementation. OVX increased the immunocontent of nuclear p-NF-κB/p65, TNF-α and IL-6 levels. VIT D partially reversed the increase in p-NF-κB/p65 immunocontent and IL-6 levels. Regarding cholinergic system, OVX caused an increase in acetylcholinesterase activity without changing acetylcholinesterase and choline acetyltransferase immunocontents. VIT D did not reverse the increase in acetylcholinesterase activity caused by OVX. These results demonstrate that OVX alters inflammatory and cholinergic parameters and that VIT D supplementation, at the dose used, partially reversed the increase in immunocontent of p-NF-Kb/p65 and IL-6 levels, but it was not able to reverse other parameters studied. Our findings may help in the understanding of the brain changes that occurs in post menopause period and open perspectives for futures research involving VIT D therapies.