Abstract

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 nontarget 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.