ABSTRACT

N-methyl-D-aspartate receptor (NMDAR) overactivation leads to free radical production, protein degradation, lipid peroxidation and DNA damage. Recently, nonsteroidal antiinflammatory drugs (NSAIDs) are suggested to be good candidates for the treatment of neurological insults. In this study, we aimed to evaluate the effect of mefenamic acid on 8-OHdG levels, the expression of poly(ADP ribose) polymerase-1 (PARP-1) and base exci-sion repair (BER) enzymes; 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1) against D-serine. Adult Sprague-Dawley rats were divided into four groups: (i) the control (n=6); (ii) D-serine (n=6); (iii) Mefenamic acid (n=6); (iv) D-serine+Mefenamic acid (n=6). Rats were decapitated 6 hours after the injections. The mRNA and protein expression levels were determined by real-time PCR and western blot techniques, respectively. D-serine increased APE1 mRNA, PARP-1 mRNA and 8-OHdG levels. APE1 and PARP-1 genes were significantly upregulated by mefenamic acid. Protein expression profiles were also consis-tent with mRNA levels. However neither mRNA nor protein levels of OGG1 were affected by D-serine or mefe-namic acid. Our results suggest that NMDA/D-serine signaling triggers DNA repair mechanisms and oxidative DNA damage simultaneously. We may conclude that mefenamic acid have a potential neuroprotective effect and assist to repair NMDAR-mediated DNA damage via modulating DNA repair mechanisms.