Neuroprotection by mefenamic acid against D-serine: Involvement of oxidative stress, inflammation and apoptosis

被引:14
作者
Armagan, Guliz [1 ]
Turunc, Ezgi [1 ]
Kanit, Lutfiye [2 ,3 ,4 ]
Yalcin, Ayfer [1 ,3 ]
机构
[1] Ege Univ, Fac Pharm, Dept Biochem, TR-35100 Izmir, Turkey
[2] Ege Univ, Fac Med, Ctr Brain Res, TR-35100 Izmir, Turkey
[3] Ege Univ, Inst Hlth Sci, Dept Neurosci, TR-35100 Izmir, Turkey
[4] Ege Univ, Fac Med, Dept Physiol, TR-35100 Izmir, Turkey
关键词
Non-steroidal antiinflammatory drugs; D-serine; inflammation; apoptosis; METHYL-D-ASPARTATE; CEREBELLAR GRANULE NEURONS; EXCITATORY AMINO-ACIDS; CELL-DEATH; RAT-BRAIN; TRANSCRIPTION FACTOR; PHOSPHOLIPASE A(2); GENE-EXPRESSION; MESSENGER-RNA; NEURODEGENERATIVE DISORDERS;
D O I
10.3109/10715762.2012.669836
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-alpha, IL-1 beta, 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 signifi cant protection against the elevation of lipid peroxidation, protein oxidation, levels of TNF-alpha, IL-1 beta 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.
引用
收藏
页码:726 / 739
页数:14
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