Toxicological Effects Of Silver Nanoparticles On The Regeneration Of Adult Zebrafish Caudal Fin

Silver nanoparticles(AgNPs)are one of the most commercialized nanomaterials,especially in healthcare,due to their excellent antibacterial properties and unique physicochemical properties.Wound dressings containing AgNPs have been applied in the treatment and management of acute and chronic wounds,such as burns and ulcers,and it was the most concerning nano-materials wound dressing.But the clinical efficacy and safety of AgNPs-coated wound dressings is still unclear.AgNPs display cytotoxicity to skin cells and tissues,but in vivo and clinical studies have shown that AgNPs-coated dressings were effective of reduce the bacterial burden and infection.Thus,the safety of AgNPs-coated dressings in use is necessary to be evaluated.Now,nanoparticles toxicity studies have mainly focused on cells and mice,and there is a lack of intuitive model.In this paper,the regeneration of amputated zebrafish fin was used as an in vivo model to evaluate the effects of AgNPs on wound healing,and we proposed a new expose method which can only treated AgNPs on the fin but whole fish.Use sodium citrate-coated AgNPs(10 nm),we evaluated the toxicological effects of silver nanoparticles on the wound healing and regeneration of adult zebrafish caudal fin.The study focused on the effects of expose AgNPs at different window stages on its toxicity,and discussed the effects of AgNPs on cell proliferation,cell apoptosis,immune cell recruitment,gene expression and wound-induced ROS production.In this paper,we made a foam model for exposure to the caudal fin of zebrafish,and a simple,rapid and reproducible exposure method was established.Combined with the easy observation property of zebrafish caudal fin regeneration model,this method can suit our requirements of toxicological experiments,and can be effectively applied to the toxicological study of nanomaterials on wound healing.We found that AgNPs treatment impaired fin regeneration,and toxic to tissue regeneration.Exposed 2?g/mL AgNPs 5 minutes at the phase of epithelialization(12-24 hours post amputation,hpa)can significantly inhibit fin regeneration,and it is no toxic effect after 24 hpa treated.Compared with 24 hpa.Compared with 24 hpa,12 hpa had stronger inhibitory effect and could continuously inhibit fin regeneration within 1-7days.Moreover,nanoparticles,but not the released ions(Ag~+)exerted the toxic effects.AgNP treatment resulted in a decrease in the cell proliferation and a increase in the cell apoptosis of the regeneration blastema.The recruitment of neutrophils was slightly increased after AgNP exposure.Additionally,AgNP treatment resulted in a decrease in the amputation-induced generation of reactive oxygen species.Based on the AgNPs expose study of the regeneration of amputated zebrafish fin,we concluded that AgNPs inhibited fin regeneration on adult zebrafish in a stage-dependent manner,and AgNP treatment resulted in a decrease in the cell proliferation of the regeneration fin.It suggested that AgNP-coated dressings should be avoid at the phase of epithelialization during wound care.