Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 16419, South Korea.
Aquatic Disease Control Division, National Institute of Fisheries Science, Busan 46083, South Korea.
Aquat Toxicol. 2018 Nov;204:70-79. doi: 10.1016/j.aquatox.2018.08.018. Epub 2018 Aug 27.
To investigate the adverse effect of two widely used pharmaceuticals, paracetamol (acetaminophen [APAP]) and oxytetracycline (OTC) on the marine rotifer Brachionus rotundiformis (B. rotundiformis), the animals were exposed to various environmentally-relevant concentrations. Up to date, acetaminophen and oxytetracycline have been considered as toxic, if used above threshold concentration, i.e. overdosed. However, this study demonstrated these two pharmaceuticals even at low concentration (i.e., μg/L scale) elicited oxidative stress through the generation of reactive oxygen species (ROS) along with the increased glutathione S-transferase activity, despite no-observed effect in in-vivo population growth. To validate the adverse effects of the two pharmaceuticals at relatively low concentrations, mRNA expression analysis was performed of the entire set of genes encoding 26 cytochrome P450s (CYPs) of phase I and 19 glutathione S-transferases (GSTs) of phase II of the rotifer B. rotundiformis. The mRNA expression analysis suggested specific genes CYP3045A2 and GSTσ1, GSTσ4, and GSTω1 take part in detoxification of APAP and OTC, resulting in no significant changes in the population growth and undetermined no observed effect concentration (NOEC) in the marine rotifer B. rotundiformis.
为了研究两种广泛使用的药物——对乙酰氨基酚(扑热息痛[APAP])和土霉素(OTC)对海洋轮虫(B. rotundiformis)的不良影响,动物被暴露于各种环境相关浓度下。迄今为止,如果使用的浓度超过阈值(即过量),人们认为对乙酰氨基酚和土霉素是有毒的。然而,本研究表明,这两种药物即使在低浓度(即μg/L 范围内)下,也会通过产生活性氧物种(ROS)并增加谷胱甘肽 S-转移酶活性,引发氧化应激,尽管在体内种群生长中没有观察到效应。为了验证这两种药物在相对较低浓度下的不良影响,对编码海洋轮虫 B. rotundiformis 全部 26 种细胞色素 P450(CYP)I 相和 19 种谷胱甘肽 S-转移酶(GST)II 相的基因进行了 mRNA 表达分析。mRNA 表达分析表明,特定基因 CYP3045A2 和 GSTσ1、GSTσ4 和 GSTω1 参与了 APAP 和 OTC 的解毒,因此海洋轮虫 B. rotundiformis 的种群生长没有显著变化,未观察到确定的无作用浓度(NOEC)。