Area of Toxicology, Faculty of Pharmacy, University of Seville, Professor García González n°2, 41012 Seville, Spain.
Aquat Toxicol. 2013 May 15;132-133:141-50. doi: 10.1016/j.aquatox.2013.02.011. Epub 2013 Feb 27.
Cylindrospermopsin (CYN) is one of the most important cyanotoxins in terms of both human health and environmental quality and is produced by several different species of cyanobacteria, including Aphanizomenon ovalisporum. The principal mechanisms of action of CYN involve inhibition of protein and glutathione synthesis. In addition, CYN-mediated genotoxicity results from DNA fragmentation. The results of both in vivo and in vitro studies suggest that oxidative stress also plays a significant role in CYN pathogenesis in fish. We investigated the protective effects of l-carnitine (LC) pre-treatment on A. ovalisporum-induced oxidative stress in cells containing CYN and deoxy-CYN, or pure standard CYN, in tilapia (Oreochromis niloticus) that had been acutely exposed via oral administration. Various oxidative stress markers, including lipid peroxidation (LPO), protein oxidation, DNA oxidation, and the ratio of reduced glutathione to oxidised glutathione (GSH/GSSG), and the activities of NADPH oxidase, superoxide dismutase (SOD), catalase (CAT), and gamma-glutamyl-cysteine synthetase (γ-GCS), were evaluated in the livers and kidneys of fish in the absence and presence of 400 or 880mgLC/kgfish/day during a 21 day period prior to CYN-intoxication. The results of our study demonstrated for the first time the beneficial antioxidant effects of LC dietary supplementation on oxidative stress status in fish. No pro-oxidant effects were detected at any of the LC doses assayed, suggesting that LC is a chemoprotectant that reduces hepatic and renal oxidative stress and may be effective when used for the prophylaxis and treatment of CYN-related intoxication in fish.
柱孢藻毒素 (CYN) 是最重要的蓝藻毒素之一，无论对人类健康还是环境质量都具有重要意义，由几种不同的蓝藻物种产生，包括鱼腥藻。CYN 的主要作用机制包括抑制蛋白质和谷胱甘肽的合成。此外，CYN 介导的遗传毒性导致 DNA 片段化。体内和体外研究的结果表明，氧化应激也在鱼类 CYN 发病机制中起重要作用。我们研究了左旋肉碱 (LC) 预处理对含有 CYN 和脱氧-CYN 或纯标准 CYN 的鱼腥藻诱导的细胞氧化应激的保护作用，这些细胞通过口服给药在罗非鱼 (Oreochromis niloticus) 中急性暴露。评估了各种氧化应激标志物，包括脂质过氧化 (LPO)、蛋白质氧化、DNA 氧化和还原型谷胱甘肽与氧化型谷胱甘肽 (GSH/GSSG) 的比值，以及 NADPH 氧化酶、超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT) 和γ-谷氨酰半胱氨酸合成酶 (γ-GCS) 的活性，在鱼的肝脏和肾脏中，在 CYN 中毒前 21 天，每天口服 400 或 880mgLC/kg 鱼，评估有无 LC。我们的研究结果首次证明了 LC 饮食补充对鱼类氧化应激状态的有益抗氧化作用。在测定的任何 LC 剂量下均未检测到促氧化作用，这表明 LC 是一种化学保护剂，可降低肝和肾的氧化应激，并且在预防和治疗鱼类与 CYN 相关的中毒时可能有效。
