title: Neuroprotection by mefenamic acid against D-serine: involvement of oxidative stress, inflammation and apoptosis.
abstract: Mefenamic acid, a non-steroidal antiinflammatory drug (NSAID), directly and dose-dependently exhibits neuroprotective activity. In our study, we investigated the effects of mefenamic acid against d-serine on oxidative stress in the hippocampus, cortex and cerebellum of rats. Furthermore, the potential inflammatory and apoptotic effects of d-serine and potential protective effect of mefenamic acid were determined at mRNA and protein levels of TNF-α, IL-1β, Bcl-2 and Bax. We found that d-serine significantly increased oxidative stress, levels of inflammation- and apoptosis-related molecules in a region specific manner. Mefenamic acid treatment provided significant protection against the elevation of lipid peroxidation, protein oxidation, levels of TNF-α, IL-1β and Bax. As a conclusion, we suggest that d-serine, as a potential neurodegenerative agent, may have a pivotal role in the regulation of oxidative stress, inflammation and apoptosis; and NSAIDs, such as mefenamic acid, may assist other therapeutics in treating disorders where d-serine-induced neurotoxic mechanisms are involved in.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey.
authors.forename: Guliz
authors.initials: G
authors.lastname: Armagan
authors.forename: Ezgi
authors.initials: E
authors.lastname: Turunc
authors.forename: Lutfiye
authors.initials: L
authors.lastname: Kanit
authors.forename: Ayfer
authors.initials: A
authors.lastname: Yalcin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008528:Mefenamic Acid / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D008528:Mefenamic Acid; D012694:Serine