Teratogenic effects induced by paracetamol, ciprofloxacin, and their mixture on Danio rerio embryos: Oxidative stress implications.

Abstract

Even though the toxic effects of paracetamol (PCM) and cipro!oxacin (CPX) have been deeply studied in the last decades, the impact of the PCM-CPX mixture may induce in aquatic organisms is poorly known. Thus, the objec- tive of this work was to investigate the teratogenic effects and oxidative stress that PCM, CPX, and their mixture induce in Danio rerio embryos. Moreover, we aimed to determine whether the PCM-CPX mixture induces more severe effects on the embryos than the individual drugs. For this purpose, zebra"sh embryos (4 hpf) were ex- posed to environmentally relevant concentrations of PCM, CPX, and their mixture until 96 hpf. In addition, at 72 hpf and 96 hpf, we also evaluated the oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase, lipid peroxidation, and hydroperoxides and carbonyl content) in the embryos. Our results demon- strated that PCM, CPX, and their mixture reduced the survival rate of embryos by up to 75%. In addition, both drugs, induced morphological alterations in the embryos, causing their death. The most observed malformations were: scoliosis, craniofacial malformations, hypopigmentation, growth retardation, pericardial edema. Concerning oxidative stress, our integrated biomarkers response (IBR) analysis demonstrated that PCM, CPX, and their mixture induce oxidative damage on the embryos. In conclusion, PCM, CPX, and their mixture can alter zebra"sh embryonic development via an oxidative stress response.Even though the toxic effects of paracetamol (PCM) and cipro!oxacin (CPX) have been deeply studied in the last decades, the impact of the PCM-CPX mixture may induce in aquatic organisms is poorly known. Thus, the objec- tive of this work was to investigate the teratogenic effects and oxidative stress that PCM, CPX, and their mixture induce in Danio rerio embryos. Moreover, we aimed to determine whether the PCM-CPX mixture induces more severe effects on the embryos than the individual drugs. For this purpose, zebra"sh embryos (4 hpf) were ex- posed to environmentally relevant concentrations of PCM, CPX, and their mixture until 96 hpf. In addition, at 72 hpf and 96 hpf, we also evaluated the oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase, lipid peroxidation, and hydroperoxides and carbonyl content) in the embryos. Our results demon- strated that PCM, CPX, and their mixture reduced the survival rate of embryos by up to 75%. In addition, both drugs, induced morphological alterations in the embryos, causing their death. The most observed malformations were: scoliosis, craniofacial malformations, hypopigmentation, growth retardation, pericardial edema. Concerning oxidative stress, our integrated biomarkers response (IBR) analysis demonstrated that PCM, CPX, and their mixture induce oxidative damage on the embryos. In conclusion, PCM, CPX, and their mixture can alter zebra"sh embryonic development via an oxidative stress response.