Transient modulation of acetylcholinesterase activity caused by exposure to dextran-coated iron oxide nanoparticles in brain of adult zebrafish

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are of great interest in nanomedicine due to their capability to act simultaneously as a contrast agent and as a targeted drug delivery system. At present, one of the biggest concerns about the use of SPIONs remains around its toxicity and, for this reason, it is important to establish the safe upper limit for each use. In the present study, SPION coated with cross-linked aminated dextran (CLIO-NH2) were synthesized and their toxicity to zebrafish brain was investigated. We have evaluated the effect of different CLIO-NH2 doses (20, 50, 100, 140 and 200mg/kg) as a function of time after exposure (one, 16, 24 and 48h) on AChE activity and ache expression in zebrafish brain. The animals exposed to 200mg/kg and tested 24h after administration of the nanoparticles have shown decreased AChE activity, reduction in the exploratory performance, significantly higher level of ferric iron in the brains and induction of casp8, casp 9 and jun genes. Taken together, these findings suggest acute brain toxicity by the inhibition of acetylcholinesterase and induction of apoptosis.