Evaluation of microplastics and pharmaceutical interactions in aquatic environments

In this study, the toxic effects of paclitaxel (PTX), one of the anticancer drugs widely used in cancer therapy, and Cremophor EL (CrEL), which is used as a solubilizing excipient in PTX formulations, were evaluated both individually and in combination. In addition, the toxic effects of mixtures of these substances with polyethylene (PE) and polystyrene (PS), selected as microplastic (MP) agents, were assessed. Furthermore, the interaction potential of these MPs with pharmaceuticals in aquatic environments containing PTX and CrEL, and the resulting toxic effects associated with these interactions, were investigated. To determine the possible effects, zebrafish (Danio rerio) which is an effective model organism, was used. Toxic effects during embryonic development due to exposure and changes in selected biochemical biomarkers were evaluated. Malformations occurring throughout embryonic development, and heart rate were examined. To assess toxic effects at the biochemical level, catalase (CAT), glutathione S-transferase (GST), carboxylesterase (CaE), acetylcholinesterase (AChE), lactate dehydrogenase (LDH), glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were analyzed as biomarkers. As a result of the tests, the LC₅₀ value calculated for PTX was determined to be 2.055 μM, while the LC₅₀ value for CrEL was 258.7 μM. In the mixture experiments, PE-MP was applied at 500 ppm and PS-MP at 52.5 ppm. Significant malformations in embryonic development were observed depending on the exposure concentrations of PTX and CrEL. PTX was found to cause yolk sac edema (YSE) and spinal curvature (SC) in particular, whereas CrEL caused pronounced lethal effects at high exposure concentrations. In mixture experiments with microplastics, PS significantly increased toxicity and, in some groups, intensified mortality rates and malformations compared to exposure to PTX or CrEL alone. In contrast, mixtures prepared with PE were found to have a more moderate effect on toxicity. Biomarker analyses revealed that exposure to PTX and CrEL, especially at high concentrations, resulted in suppression of esterase activities, alterations in oxidative stress indicators, and increases in LDH levels indicating tissue damage. Overall, the findings demonstrate that both PTX and CrEL exert toxic effects on D. rerio embryos and that the presence of microplastics in the environment, particularly PS, may enhance these effects. However, no significant difference in toxicity was observed with respect to MP type.