Hepatic positive and negative antioxidant responses in zebrafish after intraperitoneal administration of toxic microcystin-LR
Hepatic positive and negative antioxidant responses in zebrafish after intraperitoneal administration of toxic microcystin-LR
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腹腔注射有毒微囊藻毒素-LR后斑马鱼肝脏的阳性和阴性抗氧化反应
DOI：
10.1016/j.chemosphere.2014.09.079
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发表时间：
2015-02-01
期刊：
影响因子：
8.8
通讯作者：
Wu, Ning
中科院分区：
文献类型：
--
作者：
Hou, Jie;Li, Li;Wu, Ning
微囊藻毒素-LR（MC-LR）是微囊藻毒素中毒性最强、最常见的一种。为了解肝脏抗氧化解毒的分子机制，研究了雌性斑马鱼腹腔注射（i. p.）剂量分别为50和200 μ g MC-LR/kg体重（BW）。在低剂量组（50 μ g MC-LR kg（-1））中，斑马鱼在注射后最初1 h（hpi）表现出轻微的不安，肝损伤轻微且恢复快，酶活性增强，抗氧化酶基因表达上调。与此相反，高剂量的MC-LR（200 μ g MC-LR kg（-1））导致不安和疯狂的游泳，严重的肝损伤，抑制酶活性和下调抗氧化酶的基因表达。两个剂量组中的GSH耗竭可以通过增强的抗氧化反应和较高的MC结合率来解释，这表明GSH在细胞抗氧化保护和MC-LR解毒中的关键作用。本研究表明，MC-LR给药在低剂量组中引起阳性反应，但在高剂量组中引起阴性反应。低/高剂量组中的肝脏阳性/阴性反应可能分别由分子水平的抗氧化酶合成增加/减少引起。这些结果表明，抗氧化状态通过调节抗氧化酶基因的表达和活性，在斑马鱼抗MC-LR引起的氧化应激中发挥重要作用。(c)2014爱思唯尔有限公司版权所有。
Microcystin-LR (MC-LR) is the most toxic and common among microcystins. In order to understand the possible molecular mechanisms of hepatic antioxidation and detoxification, the activities and transcriptional levels of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione 5-transferases (G5T), and glutathione (GSH) contents as well as histopathological changes were studied in the liver of female zebrafish injected intraperitoneally (i.p.) at doses of 50 and 200 mu g MC-LR kg(-1) body weight (BW) respectively. In the low dose group (50 mu g MC-LR kg(-1)), zebrafish displayed a little unease at the initial 1 h post-injection (hpi), slight hepatic injury and quick recovery, and enhanced enzymatic activities and up-regulated gene expression of antioxidant enzymes. In contrast, high dose of MC-LR (200 mu g MC-LR kg(-1)) resulted in uneasiness and frantic swimming, severe hepatic injury, and suppressed enzymatic activities and down-regulated gene expression of antioxidant enzymes. GSH depletion in both dose groups may be explained by enhanced antioxidant reactions and higher rates of MC conjugation, suggesting the crucial roles of GSH in both cellular antioxidant protection and MC-LR detoxification. This study demonstrated that administration of MC-LR caused a positive response in the low dose group but a negative response in the high dose group. Hepatic positive/negative responses in the low/high dose group might result from an increased/decreased synthesis of antioxidant enzymes at the molecular level, respectively. These results illustrated that antioxidant status played an important role in zebrafish protection against MC-LR-caused oxidative stress through regulating antioxidant enzyme gene expression and activities. (c) 2014 Elsevier Ltd. All rights reserved.