Diclofenac (DCF) is a common non-steroidal anti-inflammatory drug (NSAID) that is widely used to control pain and inflammation. There has been much debate about detrimental effects of micro-pollutant such as DCF in non-target organisms. Therefore, the present systematic review (SR) evaluates the possible oxidative stress (OS) and DNA damage induced in DCF-exposed non-target organisms in aquatic environment. A systematic search was conducted in five international literature databases from 1970 to 2021. A comprehensive literature search led to the identification of 14,862 hits, 68 of which met our inclusion criteria. These studies encompassed a wide range of biological endpoints, including OS, DNA damage, cyto-genotoxicity, apoptosis, and estrogenicity potential in non-target organisms. The time, route and types of exposure to DCF was evaluated. There is a strong relationship between DCF exposure and OS, cyto-genotoxicity and DNA damage. Furthermore, there is limited evidence for estrogenic potential of DCF. According to the results of the studies considered in this work, it can be concluded that there is definitive evidence of DCF-induced OS, cyto-genotoxicity and DNA damage on the various types of non-target organisms due to the chronic exposure to DCF. The biomarkers were used to assess adverse consequences and could be used as an early warning signal for environmental monitoring of the presence of pharmaceuticals in aquatic environments. Due to the definitive evidence provided for adverse effects of DCF and multimodel mechanisms of action, it is essential to take a degree of caution to use the DCF and develop the advanced treatment technologies to prevent the release of this type of contaminant to aquatic environments.

双氯芬酸 (DCF) 是一种常见的非甾体抗炎药 (NSAID)，广泛用于控制疼痛和炎症。关于微污染物（如 DCF）对非目标生物的有害影响的争论很多。因此，本系统评价 (SR) 评估了水生环境中暴露于 DCF 的非目标生物中可能引起的氧化应激 (OS) 和 DNA 损伤。从 1970 年到 2021 年，在五个国际文献数据库中进行了系统搜索。全面的文献搜索导致确定了 14,862 个匹配项，其中 68 个符合我们的纳入标准。这些研究涵盖了广泛的生物学终点，包括非靶标生物的 OS、DNA 损伤、细胞遗传毒性、细胞凋亡和雌激素潜力。评估了接触 DCF 的时间、途径和类型。DCF 暴露与 OS、细胞遗传毒性和 DNA 损伤之间存在密切关系。此外，关于 DCF 的雌激素潜力的证据有限。根据这项工作中考虑的研究结果，可以得出结论，由于长期暴露于 DCF，存在 DCF 诱导的 OS、细胞遗传毒性和 DNA 损伤对各种类型的非目标生物的明确证据。生物标志物用于评估不良后果，并可用作水环境中药物存在的环境监测的早期预警信号。由于为 DCF 和多模式作用机制的不利影响提供了明确的证据，