Agharahimi Maryam, Badisa Ramesh B, Mazzio Elizabeth, Soliman Karam F, Goodman Carl B
College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA.
Biomed Rep. 2021 May;14(5):45. doi: 10.3892/br.2021.1421. Epub 2021 Mar 16.
Cocaine is a highly addictive drug that mediates its effect through altering dopamine metabolism in the central nervous system (CNS), resulting in a feeling of euphoria. Owing to its high lipophilicity, cocaine easily crosses the blood brain barrier of the CNS and reaches various domains of the brain, where it can trigger cellular damage. Cocaine-induced CNS damage may arise due to increased levels of free radicals and nitric oxide (NO) in immunecompetent astroglial cells. In the present study, the potential ability of cocaine to exacerbate the production of inflammatory products, primarily superoxide free radicals (O ), hydrogen peroxide (HO) and NO/nitrite (NO ) was examined in rat astroglia-like cells challenged with lipopolysaccharide (LPS), a bacterial endotoxin, and interferon gamma (IFNγ), a pro-inflammatory cytokine. Furthermore, the role of cocaine in increasing the expression of hypoxia inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF) in cells was also determined. First, the viability of the cells was assessed when treated with cocaine (0.5-7 mM) for 24 and 48 h. The results showed that cocaine toxicity was both time and dose-dependent. In subsequent studies, cells were challenged with or without LPS and IFNγ, followed by co-treatment with cocaine (1-4 mM) for 24 h. Cocaine treatment did not increase O or HO production in the challenged or unchallenged cells. Similarly, cocaine treatment did not increase NO/NO production in the unchallenged cells; however, NO/NO levels in the challenged cells was increased 40-50-fold upon cocaine treatment compared with the corresponding unchallenged group. The HIF-1α and VEGF levels were significantly increased in the challenged cells at higher cocaine doses compared with the unchallenged cells. Since high concentrations of NO are associated with inflammation, the high levels of NO production observed in the present study suggested that cocaine may have potentiated the inflammatory response in the challenged astroglia-like cells.
可卡因是一种极易上瘾的药物，它通过改变中枢神经系统（CNS）中的多巴胺代谢来发挥作用，从而产生欣快感。由于其高亲脂性，可卡因很容易穿过中枢神经系统的血脑屏障，到达大脑的各个区域，在那里它会引发细胞损伤。可卡因诱导的中枢神经系统损伤可能是由于免疫活性星形胶质细胞中自由基和一氧化氮（NO）水平升高所致。在本研究中，检测了可卡因在受到细菌内毒素脂多糖（LPS）和促炎细胞因子干扰素γ（IFNγ）刺激的大鼠星形胶质样细胞中加剧炎症产物产生的潜在能力，这些炎症产物主要是超氧自由基（O ）、过氧化氢（HO）和NO/亚硝酸盐（NO ）。此外，还确定了可卡因在增加细胞中缺氧诱导因子-1（HIF-1α）和血管内皮生长因子（VEGF）表达方面的作用。首先，评估细胞在用可卡因（0.5 - 7 mM）处理24小时和48小时后的活力。结果表明，可卡因毒性具有时间和剂量依赖性。在随后的研究中，细胞在有或没有LPS和IFNγ的情况下受到刺激，然后与可卡因（1 - 4 mM）共同处理24小时。可卡因处理并未增加受刺激或未受刺激细胞中O 或HO的产生。同样，可卡因处理并未增加未受刺激细胞中NO/NO 的产生；然而，与相应的未受刺激组相比，受刺激细胞中可卡因处理后NO/NO 的水平增加了40 - 50倍。与未受刺激的细胞相比，在较高可卡因剂量下，受刺激细胞中的HIF-1α和VEGF水平显著升高。由于高浓度的NO与炎症有关，本研究中观察到的高水平NO产生表明可卡因可能增强了受刺激的星形胶质样细胞中的炎症反应。
