Chang J Y, Liu L Z
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Neurochem Int. 1998 Apr;32(4):317-23. doi: 10.1016/s0197-0186(97)00103-4.
Cultured rat cerebellar granule cells were used to determine the potential neurotoxicity of cholesterol oxides. The cholesterol oxides tested included: 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH- and 25-OH- cholesterol. Among them, 7-beta-OH- and 7-keto-cholesterol were the most efficacious in causing neuronal death such that 20 microg/ml (50 microM) of these agents killed more than 80% of cells in 2 days. 7-beta-OH-cholesterol at this concentration killed 50% of cells in approximately 7 h. A number of pharmacological agents were tested for their abilities to prevent neuronal death induced by cholesterol oxides. Among them, aurintricarboxylic acid, vitamin E and methyl-beta-cyclodextrin were able to prevent cholesterol oxide-induced neurotoxicity in a dose-dependent manner. These results suggest that, in addition to causing pathological changes in cells directly involved in atherosclerosis, cholesterol oxides may induce toxicity in neurons of the central nervous system.
培养的大鼠小脑颗粒细胞被用于确定胆固醇氧化物的潜在神经毒性。所测试的胆固醇氧化物包括：7-β-羟基-、7-酮基-、19-羟基-、22(R)-羟基-、22(S)-羟基-和25-羟基-胆固醇。其中，7-β-羟基-和7-酮基-胆固醇在导致神经元死亡方面最为有效，以至于20微克/毫升（50微摩尔）的这些物质在2天内杀死了超过80%的细胞。该浓度下的7-β-羟基-胆固醇在约7小时内杀死了50%的细胞。测试了多种药物预防胆固醇氧化物诱导的神经元死亡的能力。其中，金精三羧酸、维生素E和甲基-β-环糊精能够以剂量依赖的方式预防胆固醇氧化物诱导的神经毒性。这些结果表明，除了在直接参与动脉粥样硬化的细胞中引起病理变化外，胆固醇氧化物可能还会在中枢神经系统的神经元中诱导毒性。
