Ding W X, Shen H M, Zhu H G, Ong C N
School of Public Health, Shanghai Medical University, People's Republic of China.
Environ Res. 1998 Jul;78(1):12-8. doi: 10.1006/enrs.1998.3843.
Contamination of water by cyanobacteria (blue-green algae) is a serious health problem around the world, largely due to the toxic effects of microcystins, a group of potent hepatotoxins. However, the mechanisms responsible for the cytotoxicity of microcystins have not been fully elucidated. In the present study, oxidative damage caused by lyophilized freshwater cyanobacteria extract was evaluated on primary cultured rat hepatocytes. A time- and dose-dependent increase of lactate dehydrogenase (LDH) leakage was observed in hepatocytes treated with cyanobacteria extract. Lipid peroxidation, a main manifestation of oxidative damage, was also studied and a time- and dose-dependent increase in malondiadehyde was observed. In addition, by using a fluorescent probe, 2',7'-dichlorofluorescein diacetate, it was found that cyanobacteria extract was able to enhance intracellular production of reactive oxygen species (ROS) in a dose- and time-dependent manner. Moreover, desferrioxamine, a specific iron chelator, could significantly decrease LDH leakage and ROS production caused by cyanobacteria extract treatment. These findings thus provide experimental evidence that oxidative damage is involved in cyanobacteria extract-induced hepatotoxicity. The understanding of this mechanism is believed to be beneficial to the prevention and control of the toxicity of microcystin and cyanobacteria contamination.
蓝藻(蓝绿藻)对水的污染是一个全球性的严重健康问题,这主要归因于微囊藻毒素的毒性作用,微囊藻毒素是一类强效肝毒素。然而,微囊藻毒素细胞毒性的作用机制尚未完全阐明。在本研究中,对原代培养的大鼠肝细胞评估了冻干淡水蓝藻提取物引起的氧化损伤。在用蓝藻提取物处理的肝细胞中观察到乳酸脱氢酶(LDH)泄漏呈时间和剂量依赖性增加。还研究了氧化损伤的主要表现——脂质过氧化,观察到丙二醛呈时间和剂量依赖性增加。此外,通过使用荧光探针2',7'-二氯荧光素二乙酸酯,发现蓝藻提取物能够以剂量和时间依赖性方式增强细胞内活性氧(ROS)的产生。而且,特异性铁螯合剂去铁胺可显著降低蓝藻提取物处理引起的LDH泄漏和ROS产生。因此,这些发现提供了实验证据,表明氧化损伤参与了蓝藻提取物诱导的肝毒性。相信对这一机制的理解将有助于预防和控制微囊藻毒素的毒性以及蓝藻污染。