PMID- 29846873 OWN - NLM STAT- MEDLINE DCOM- 20190514 LR - 20190514 IS - 1559-1174 (Electronic) IS - 1535-1084 (Linking) VI - 20 IP - 3 DP - 2018 Sep TI - Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA. PG - 328-342 LID - 10.1007/s12017-018-8496-8 [doi] AB - Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (omega-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells. To this end, mouse microglial BV-2 cells were stimulated with either lipopolysaccharide (LPS) or hydrogen peroxide (H(2)O(2)) and co-incubated with DHA 50 ppm of PhA (DHA (PhA:50)) or DHA 500 ppm of PhA (DHA (PhA:500)). Cell viability, superoxide anion (O(2)(-)) production, Interleukin 6 (L-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glutathione peroxidase (GtPx), glutathione reductase (GtRd), Caspase-3, and the brain-derived neurotrophic factor (BDNF) protein expression were explored. Low PhA-concentrated DHA protected against LPS or H(2)O(2)-induced cell viability reduction in BV-2 activated cells and O(2)(-) production reduction compared to DHA (PhA:500). Low PhA-concentrated DHA also decreased COX-2, IL-6, iNOS, GtPx, GtRd, and SOD-1 protein expression when compared to DHA (PhA:500). Furthermore, low PhA-concentrated DHA increased BDNF protein expression in comparison to DHA (PhA:500). The study provides data supporting the beneficial effect of low PhA-concentrated DHA in neurotoxic injury when compared to a standard PhA-concentrated DHA in activated microglia. FAU - Ruiz-Roso, Maria Belen AU - Ruiz-Roso MB AD - Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain. FAU - Olivares-Alvaro, Elena AU - Olivares-Alvaro E AD - Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain. FAU - Quintela, Jose Carlos AU - Quintela JC AD - Natac Pharma S.L., 28923, Alcorcon, Madrid, Spain. FAU - Ballesteros, Sandra AU - Ballesteros S AD - Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain. FAU - Espinosa-Parrilla, Juan F AU - Espinosa-Parrilla JF AD - Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, 08035, Barcelona, Spain. FAU - Ruiz-Roso, Baltasar AU - Ruiz-Roso B AD - Department of Nutrition and Bromatology I (Nutrition), Faculty of Pharmacy, Complutense University, 28040, Madrid, Spain. FAU - Lahera, Vicente AU - Lahera V AD - Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain. FAU - de Las Heras, Natalia AU - de Las Heras N AD - Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain. FAU - Martin-Fernandez, Beatriz AU - Martin-Fernandez B AD - Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain. bmartinfernandez@med.ucm.es. AD - Natac Biotech S.L., 28923, Alcorcon, Madrid, Spain. bmartinfernandez@med.ucm.es. LA - eng GR - RTC-2014-1689-1/This work was supported by grants from "Programa Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad, Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2013-2016"./International PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180530 PL - United States TA - Neuromolecular Med JT - Neuromolecular medicine JID - 101135365 RN - 0 (Antioxidants) RN - 0 (Bdnf protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (CD11b Antigen) RN - 0 (Lipopolysaccharides) RN - 0 (Neuroprotective Agents) RN - 11062-77-4 (Superoxides) RN - 14721-66-5 (Phytanic Acid) RN - 25167-62-8 (Docosahexaenoic Acids) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Animals MH - Antioxidants/metabolism MH - Brain-Derived Neurotrophic Factor/biosynthesis MH - CD11b Antigen/biosynthesis MH - Cell Line MH - Cell Survival/drug effects MH - Docosahexaenoic Acids/*pharmacology/therapeutic use MH - Hydrogen Peroxide/pharmacology MH - Inflammation/drug therapy/metabolism MH - Lipopolysaccharides/pharmacology MH - Mice MH - Microglia/*drug effects/metabolism MH - *Neuroprotection MH - Neuroprotective Agents/*pharmacology/therapeutic use MH - Neurotoxicity Syndromes/drug therapy MH - Osmolar Concentration MH - Phytanic Acid/*pharmacology/therapeutic use MH - Superoxides/metabolism OTO - NOTNLM OT - BDNF OT - DHA OT - Microglia OT - Oxidation OT - Phytanic acid EDAT- 2018/05/31 06:00 MHDA- 2019/05/15 06:00 CRDT- 2018/05/31 06:00 PHST- 2017/11/13 00:00 [received] PHST- 2018/05/24 00:00 [accepted] PHST- 2018/05/31 06:00 [pubmed] PHST- 2019/05/15 06:00 [medline] PHST- 2018/05/31 06:00 [entrez] AID - 10.1007/s12017-018-8496-8 [pii] AID - 10.1007/s12017-018-8496-8 [doi] PST - ppublish SO - Neuromolecular Med. 2018 Sep;20(3):328-342. doi: 10.1007/s12017-018-8496-8. Epub 2018 May 30.