Attenuating effect of N-acetyl-L-cysteine against acute cocaine toxicity in rat C6 astroglial cells
Attenuating effect of N-acetyl-L-cysteine against acute cocaine toxicity in rat C6 astroglial cells
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DOI：
10.3892/ijmm.2013.1391
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发表时间：
2013-08-01
影响因子：
5.4
通讯作者：
Fitch-Pye, Cheryl A.
中科院分区：
文献类型：
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作者：
Badisa, Ramesh B.;Goodman, Carl B.;Fitch-Pye, Cheryl A.
星形胶质细胞是哺乳动物大脑中最丰富的细胞类型之一，在神经元存活和维持基本的电路模式中发挥作用。到目前为止，还没有关于可卡因对培养物中这些细胞的短期影响的研究。本研究旨在研究急性可卡因（1小时）处理对大鼠C6星形胶质细胞的细胞活力。此外，N-乙酰-L-半胱氨酸（NAC）对可卡因诱导的毒性的潜在影响进行了研究。观察到2、3和4 mM可卡因急性暴露1小时会导致细胞活力呈剂量依赖性下降，LC 50为2.857 mM。此外，可卡因处理还会导致细胞中谷胱甘肽（GSH）水平下降。结果发现，可卡因在其暴露于细胞期间不表现出促氧化活性。急性可卡因暴露没有诱导细胞中一氧化氮（NO）的释放。NAC的5点（1-5 mM）剂量-反应曲线清楚地表明对星形胶质细胞活力无不良影响。用5 mM NAC预处理细胞30 min，然后弃去，并暴露于可卡因（2-4 mM）1 h，可使细胞免受90%的细胞毒性。用NAC-可卡因混合物处理细胞提供100%的保护。进一步的研究表明，NAC的保护作用是通过增加细胞中的GSH水平。我们的研究结果表明，GSH水平下降可能代表细胞死亡的潜在病理之一，抗氧化剂化合物，增加GSH的生产可以保护对可卡因诱导的毒性，通过促进在星形胶质细胞中的促生存作用。
Astroglial cells are one of the most abundant cell types in the mammalian brain functioning in neuronal survival and in maintenance of fundamental patterns of circuitry. To date, no study has been conducted regarding the short-term impact of cocaine on these cells in cultures. The present study aimed to investigate acute cocaine (1 h) treatment on cell viability in rat C6 astroglial cells. In addition, the potential effect of N-acetyl-L-cysteine (NAC) against cocaine-induced toxicity was studied. It was observed that 1 h of acute cocaine exposure at 2, 3 and 4 mM caused a dose-dependent decrease in cell viability with an LC50 of 2.857 mM. Furthermore, cocaine treatment caused a decrease in glutathione (GSH) levels in the cells. It was found that cocaine did not exhibit pro-oxidant activity during its exposure to cells. Acute cocaine exposure did not induce nitric oxide (NO) release in the cells. A 5-point (1-5 mM) dose-response curve of NAC clearly indicated no adverse effect on astroglial cell viability. Pretreatment of cells with 5 mM NAC for 30 min, followed by its discard, and exposure to cocaine (2-4 mM) for 1 h protected cells against cytotoxicity by 90%. Treatment of cells with NAC-cocaine mixture rendered 100% protection. Further investigations revealed that the protection by NAC was through the increased GSH levels in the cells. Our results indicate that decreased GSH levels may represent one of the underlying pathologies of cell death and that antioxidant compounds which increase the GSH production could protect against cocaine-induced toxicity by promoting a pro-survival role in astroglial cells.