Effect of ibuprofen on the behavior, histopathology, antioxidant system, DNA damage, and apoptosis of Asian freshwater clams (Corbicula fluminea)

The accumulation of ibuprofen (IBU) in freshwater sediments poses significant risks to benthic bivalves, yet its chronic ecological impacts remain insufficiently studied. Here, Asian clams (Corbicula fluminea) were exposed to 0, 20, 200, and 2000 µg/L IBU for 28 days. The viscera were identified as the primary target organ for IBU toxicity, with bioconcentration factors (BCFs) ranging from 3.03–6.05 across treatments and a 1.3- to 3.3-fold increase in in digestive gland vacuolation damage. Chronic IBU exposure also induced neurotoxicity, evidenced by acetylcholinesterase inhibition, and potentially associated behavioral disturbances. Filtration and burrowing rates decreased significantly at 200 and 2000 µg/L, while escape rates increased, reflecting a trade-off between avoidance and burrowing under stress. At 20 µg/L, escape fluctuations were most pronounced, suggesting sub-threshold behavioral modulation. The trade-off between escape and burrowing highlights the adaptive yet costly responses of bivalves to pharmaceutical stress. Transcriptomic profiling demonstrated marked enrichment of apoptotic and pro-inflammatory pathways. Notably, while antioxidant defenses remained unaltered in clams, IBU exposure consistently upregulated COX-2 activity, with concomitant induction of genotoxic effects evidenced by DNA strand breakage and activation of caspase-9 mediated intrinsic apoptotic pathways. This work provides critical insights for managing pharmaceutical contamination in freshwater ecosystems and protecting benthic biodiversity and ecosystem functions.