SIÇAN PRİMER KORTEKS NÖRON KÜLTÜRÜNDE GLUTAMAT TOKSİSİTESİNE KARŞI KLORZOKSAZONUN NÖROPROTEKTİF ETKİSİ

Abstract

Glutamat (Glut) toksisitesi, nörolojik hastalıklara zemin hazırlayan ana sebeplerden biridir. Klorzoksazon (CZ), akut ve kronik morluklar ve burkulmalarla ilişkili ağrı ve iltihabı azaltmak için kullanılan kas gevşeticidir. Burada, yenidoğan serebral kortekste Glut'un neden olduğu nörodejenerasyonu tersine çevirmek için uygulanan CZ'nin nöroprotektif etkisini anti-inflamatuar ve antioksidan mekanizmalar yoluyla araştırmayı amaçladık. Yenidoğan kortikal nöronları Glut’a maruz bırakıldı ve CZ’nin Glut toksisitesi üzerindeki etkisini değerlendirmek için CZ çeşitli dozlarda (10, 20 ve 40 µM) uygulandı. Ardından hücre canlılığı, oksidatif stres ve inflamasyondaki değişiklikleri inceledik. Hücre canlılık analizimiz, CZ’nin Glut kaynaklı nöranal hasardan hücreleri koruduğunu göstermiştir. Ayrıca CZ’nin nöroprotektif özelliği MDA, MPO, CAT, GSH, GPx ve SOD gibi oksidatif ve antioksidan parametrelerin incelenmesi ile değerlendirildi. Elde edilen veriler doğrultusunda,hücre canlılık oranı Glut grubunda % 60'a kadar düştüğü gözlendi. Ancak CZ uygulaması ile birlikte hücre canlılığında en anlamlı artış 40 μM dozunda (%86) görülürken, en az artış 10 μM CZ (%77) görüldü. Ayrıca CZ'nin oksidatif parametreleri ve inflamasyonu azaltırken, antioksidan parametrelerin aktivitesini arttırdığını kanıtladı. Bu nedenle mevcut bulgular toplu olarak CZ'nin Glut kaynaklı hasarı yenidoğan kortikal nöronlarında güçlü bir şekilde önlediğini göstermiştir. Mevcut çalışma, Glut eksitotoksisitesine maruz kalan yenidoğan korteks nöronlarında CZ’nin koruyucu etkisini gösteren ilk çalışmadır ve CZ’nin terapötik bir ajan olarak kullanılabileceğini göstermektedir.

Keywords

• Klorzoksazon
• korteks
• glutamat
• nöron

NEUROPROTECTIVE EFFECT OF CHLORZOXAZONE AGAINST GLUTAMATE TOXICITY IN RAT PRIMARY CORTEX NEURON CULTURE

Abstract

Glutamate (Glut) toxicity is one of the main causes of neurological diseases. Chlorzoxazone (CZ) is a muscle relaxant used to decrease pain and inflammation associated with acute and chronic twists and bruises. Here, we objected to research the neuroprotective effect of CZ applied to reverse Glut-induced neurodegeneration in the neonatal cerebral cortex through anti-inflammatory and antioxidant mechanisms. Neonatal cortical neurons were exposed to Glut and different doses of CZ (10, 20, and 40 µM) were applied to assess the effect of CZ on Glut toxicity. We then examined changes in cell viability, inflammation, and oxidative stress. Our cell viability analysis showed that CZ protected cells from Glut-induced neuronal damage. In addition, the neuroprotective properties of CZ were evaluated by examining oxidative and antioxidant parameters such as MDA, MPO, CAT, GSH, GPx, and SOD. In line with the data obtained, it was observed that the cell viability rate decreased to 60% in the Glut group. However, with CZ application, the most significant increase in cell viability was seen at the 40 μM dose (86%), while the least increase was seen at 10 μM CZ (77%). It also proved that CZ increased the activity of antioxidant parameters while reducing oxidative parameters and inflammation. Therefore, the present findings collectively demonstrated that CZ potently inhibits Glut-induced injury in neonatal cortical neurons. The present work is the initial to show the protective effect of CZ in neonatal cortical neurons exposed to Glut excitotoxicity and suggesting that CZ may be used as a therapeutic agent.

Keywords

• Chlorzoxazone
• cortex
• glutamate
• neuron

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