Toxic effects of naproxen on the intestine of the goldfish, Carassius auratus

Background Extensive use of the non-steroidal anti-inflammatory drug (NSAID) naproxen greatly increases the likelihood of its release into the ambient water environment. Although naproxen has a variety of toxic effects on aquatic organisms, little is known about its effects on the gastrointestinal system of aquatic organisms. Objective In the present study, adult goldfish were exposed to naproxen at concentrations of 200 and 1000 mu g/L for 7 and 21 days, respectively, to investigate the effects of naproxen on histopathology, antioxidant system, and gut microbiota of goldfish's intestine. Results Histological analysis and qPCR analysis showed that exposure to varying naproxen concentrations and exposure times resulted in damage to goldfish intestinal tissue. Naproxen exposure induced more vacuolation and reduced the number of goblet cells to change the morphology of the intestine. Meanwhile, the expression of antioxidant enzyme-related genes was up-regulated, predicting that the activity of antioxidant enzymes might be enhanced. High-throughput 16S rDNA sequencing showed that naproxen stress under different conditions altered intestinal bacterial diversity, and microbial community composition, especially impacting the phyla Fusobacteria, Firmicutes, Actinobacteria and Proteobacteria and genera Cetobacterium, ZOR0006, Aeromonas and Rhodococcus, and significantly enhanced the functions of replication, recombination and repair, biosynthesis of secondary metabolites and biosynthesis of antibiotics and significantly weakened the functions of energy production and conversion, carbohydrate transport and metabolism and cell wall/membrane/envelope biogenesis of the gut microbiota. Conclusion These results indicated that naproxen stress can change the intestinal tissue structure, affect the intestinal antioxidant system, and change the composition of intestinal microorganisms, thereby impeding the normal physiological function of the intestine and threatening the health of fish.