Effect of Mefenamic Acid on Some of The Base Excision Repair Enzymes Against D-Serine-Induced Neurotoxicity

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 mechanism

Nicotine increased VEGF and MMP2 levels in the rat eye and kidney

Chronic cigarette smoking affects many tissues negatively. Nicotine in tobacco has negative effects on tissues, kidneys, and eyes especially, where microcirculation is vitally important for the survival and functioning. It is known that appropriate vascular endothelial growth factor (VEGF) and (matrix metalloproteinase 2) MMP2 levels are required for suitable vascularity and enough microcirculation. The aim of this study was to investigate the effect of nicotine on VEGF and MMP2 levels in kidney and eyes, where microcirculation is very important for their function. The nicotine was given into drinking water, to male and female rats for 6 weeks. During the first 2 weeks, the nicotine concentration was 10 mg/L, then was given at a fixed dose of 20 mg/L until the end of the experiment. The VEGF and MMP2 levels were increased in kidney tissue of both genders as a result of given nicotine. MMP2 levels were also increased in the eye tissue for both genders similarly. However, VEGF levels increased in the eye tissue with nicotine in males, whereas it did not change in females. The use of nicotine made VEGF and MMP2 levels increase in kidney tissue in both genders of rats. This increase in VEGF was observed only in male eye tissue, not in females. According to our findings, it can be suggested that nicotine has negative effects on microvascular circulation by increasing VEGF and MMP2 levels. In addition, it should be pointed out that estrogen might have protective effects on female eye tissue. Further studies are necessary to understand the complex relationship between the role of nicotine and estrogen on eye and kidney tissues