Laboratorio de Toxicología Ambiental, Departamento de Farmacia, Facultad de Química, Universidad Autónoma del Estado de México, Mexico.
Ecotoxicol Environ Saf. 2013 Jun;92:32-8. doi: 10.1016/j.ecoenv.2013.01.025. Epub 2013 Mar 6.
Due to its analgesic properties, diclofenac (DCF) is one of the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs). While residue from this pharmaceutical agent has been found in diverse water bodies in various countries, there is not enough information of its potential toxicity on aquatic organisms, particularly in species which are economically valuable due to their high consumption by humans, such as the common carp Cyprinus carpio. This study aimed to evaluate potential DCF-induced oxidative stress in brain, liver, gill and blood of C. carpio. The median lethal concentration of DCF at 96h (96-h LC50) was determined and used to establish the concentration equivalent to the lowest observed adverse effect level (LOAEL). Carp specimens were exposed to this concentration for different exposure times (12, 24, 48, 72 and 96h) and the following biomarkers were evaluated: lipid peroxidation (LPX) and the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Also, the DCF and 4-hydroxy DCF was determined by LC-MS/MS. Results show a statistically significant LPX increase (P<0.05) in liver and gill mainly as well as significant changes in the activity of the antioxidant enzymes evaluated in these organs, with respect to controls (P<0.05). The DCF concentrations decreased in water system and increased in the carp. The DCF biotransformation to 4-hydroxy DCF was observed to 12h. The pharmaceutical agent DCF is concluded to induce oxidative stress on the common carp C. carpio, with the highest incidence of oxidative damage occurring in liver and gill. Furthermore, the biomarkers employed in this study are useful in the assessment of the environmental impact of this agent on aquatic species.
由于其镇痛特性，双氯芬酸（DCF）是最常用的非甾体抗炎药（NSAIDs）之一。虽然这种药物在不同国家的各种水体中都有发现，但关于其对水生生物的潜在毒性的信息还不够充分，特别是对于那些由于人类高消费而具有经济价值的物种，如鲤鱼（Cyprinus carpio）。本研究旨在评估 DCF 对鲤鱼大脑、肝脏、鳃和血液中潜在的氧化应激。确定了 DCF 在 96 小时（96-h LC50）的半致死浓度，并将其用作建立最低观察到的不良效应水平（LOAEL）的浓度当量。将鲤鱼暴露于该浓度下不同的暴露时间（12、24、48、72 和 96 小时），并评估以下生物标志物：脂质过氧化（LPX）和抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性。此外，还通过 LC-MS/MS 测定了 DCF 和 4-羟基 DCF。结果表明，肝脏和鳃中的 LPX 增加（P<0.05），以及这些器官中评估的抗氧化酶活性发生显著变化（P<0.05），与对照组相比。DCF 浓度在水系统中降低，在鲤鱼体内增加。观察到 DCF 向 4-羟基 DCF 的生物转化在 12 小时内发生。结论是，DCF 药物会对鲤鱼（Cyprinus carpio）造成氧化应激，肝脏和鳃中氧化损伤的发生率最高。此外，本研究中使用的生物标志物可用于评估该药物对水生物种的环境影响。
