Grape Seed Extract Pretreatment Prevents Mitochondrial Dysfunction and NLRP3 Inflammasome-Induced Inflammatory Response in Glial Cells Exposed to Paroxetine and Quinolinic Acid.

Depression is a neuropsychiatric disorder that affects thousands of people around the world. Drug therapy is the main approach for treating this disease, but its use can cause side effects on cells. This study aimed to examine the impact of antidepressant drugs from different classes on glial (BV-2) cells in the presence or absence of grape seed extract (GSE) and quinolinic acid (QA; 1.5 mM). Cells were treated with GSE (50 μg/mL; 23 h) and then exposed to non-cytotoxic concentrations of bupropion, imipramine, paroxetine, trazodone, and venlafaxine (27-181 µM; 1 h). Principal Component Analysis (PCA) was conducted to demonstrate the best combination of drug and extract treatment. Cell viability, adenosine triphosphate (ATP) production, reactive oxygen species (ROS) and nitric oxide (NO) levels, oxidative damage to lipids (TBARS), superoxide dismutase (SOD) activity, apoptosis, and NLR family pyrin domain containing 3 (NLRP3) genetic expression were evaluated by spectrophotometry, qRT-PCR, or flow cytometry. Mitochondrial markers (CI: NADH-CoQ reductase and CIV: cytochrome c oxidase) were also studied. GSE prevented the increment in levels of ROS (13.73-72.11%), TBARS (44.1-92.77%), NO (9.5-16%), SOD (68.44-212.29%) activity, and apoptosis (10.06-17.3%) caused by antidepressant drugs. Furthermore, it prevented impairments in complexes I (22-71.5%) and IV (7.5-92.5%) activities and ATP production (8-46%). GSE also prevented the NLRP3 overexpression in BV-2 activated by QA (62%), and paroxetine (46%), defined by PCA. Our study evidences that GSE can restore redox equilibrium and prevent inflammation caused by antidepressants and/or QA in a glial microenvironment.