Banaee_2026_J.Appl.Toxicol__

Microplastics (MPs) are emerging contaminants in aquatic ecosystems and are able to modify the bioavailability and toxicity of co-occurring chemicals. In the present study, it was investigated whether high-density polyethylene (HDPE)-MPs exacerbate the toxicological effects of the pyrethroid insecticide deltamethrin in juvenile common carp (Cyprinus carpio). Fish (n = 270; 25 +/- 5 g) were randomly allocated to a 2 x 3 factorial design (three replicates per group; 15 fish per tank) and exposed for 30 days to sub-lethal deltamethrin (12.5 microg/L; 10% of 96-h LC50) and/or HDPE-MPs (0, 350, or 700 microg/L; 200-250 microm). Hepatic detoxification- and antioxidant-related gene expression was quantified, together with redox status, oxidative damage, and plasma biochemical biomarkers of organ function and injury. Deltamethrin and MPs alone altered transcriptional and biochemical endpoints, while co-exposure (particularly with 700 microg/L MPs) produced the most pronounced responses, including stronger induction of detoxification/metal-binding genes, reduced overall antioxidant capacity, and marked increases in lipid peroxidation and protein oxidation. Plasma activities of AST, ALT, ALP, LDH, GGT, and CK increased, and butyrylcholinesterase was inhibited, indicating cellular membrane damage and multi-organ dysfunction. Changes in circulating metabolites and creatinine further supported hepatic and renal impairment, and significant interaction effects for multiple endpoints suggested potentiation of deltamethrin toxicity by MPs. Overall, HDPE MPs act as relevant co-stressors that intensify deltamethrin-driven toxicity in fish, underscoring the need for mixture-aware monitoring and risk assessment in contaminated freshwater environments.