Badisa Ramesh B, Fitch-Pye Cheryl A, Agharahimi Maryam, Palm Donald E, Latinwo Lekan M, Goodman Carl B
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Department of Biological Science, Florida State University, Tallahassee, FL 32310, USA.
Mol Med Rep. 2014 Nov;10(5):2287-92. doi: 10.3892/mmr.2014.2524. Epub 2014 Aug 28.
Cocaine is a powerful addictive drug, widely abused in most Western countries. It easily reaches various domains within and outside of the central nervous system (CNS), and triggers varying levels of cellular toxicity. No pharmacological treatment is available to alleviate cocaine-induced toxicity in the cells without side-effects. Here, we discerned the role of milk thistle (MT) seed extract against cocaine toxicity. First, we investigated acute cytotoxicity induced by treatment with 2, 3 and 4 mM cocaine for 1 h in astroglial, liver and kidney cells in vitro, and then in living shrimp larvae in vivo. We showed that astroglial cells are more sensitive to cocaine than liver, kidney cells or larvae. Cocaine exposure disrupted the general architecture of astroglial cells, induced vacuolation, decreased cell viability, and depleted the glutathione (GSH) level. These changes may represent the underlying pathology of cocaine in the astrocytes. By contrast, MT pretreatment (200 µg/ml) for 30 min sustained the cell morphological features and increased both cell viability and the GSH level. Besides its protective effects, the MT extract was revealed to be non-toxic to astroglial cells, and displayed high free-radical scavenging activity. The results from this study suggest that enhanced GSH level underlies cell protection, and indicate that compounds that promote GSH synthesis in the cells may be beneficial against cocaine toxicity.
可卡因是一种强效成瘾性药物,在大多数西方国家被广泛滥用。它能够轻易到达中枢神经系统(CNS)内外的各个区域,并引发不同程度的细胞毒性。目前尚无无副作用的药物治疗方法来减轻可卡因对细胞造成的毒性。在此,我们探究了水飞蓟(MT)种子提取物对可卡因毒性的作用。首先,我们在体外分别用2、3和4 mM可卡因处理星形胶质细胞、肝细胞和肾细胞1小时,然后在活体虾幼虫体内进行处理,以此研究急性细胞毒性。我们发现星形胶质细胞对可卡因的敏感性高于肝细胞、肾细胞或幼虫。接触可卡因会破坏星形胶质细胞的整体结构,导致空泡形成,降低细胞活力,并耗尽谷胱甘肽(GSH)水平。这些变化可能代表了可卡因在星形胶质细胞中的潜在病理机制。相比之下,用MT(200 µg/ml)预处理30分钟可维持细胞形态特征,并提高细胞活力和GSH水平。除了其保护作用外,MT提取物对星形胶质细胞无毒,且具有较高的自由基清除活性。本研究结果表明,GSH水平的提高是细胞保护的基础,并表明能促进细胞内GSH合成的化合物可能对可卡因毒性具有有益作用。