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Nephrotoxicity and Genotoxicity of Silver Nanoparticles in Juvenile Rats and Possible Mechanisms of Action
Authors:Ye Liu  Li Sun  Guili Yang  Zhuo Yang
Affiliation:1.Tianjin Medical University General Hospital, Ministry of Education and Tianjin City, Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Repair and Regeneration in Central Nervous System, Tianjin, China;2.Nankai University College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Tianjin, China
Abstract:Because of their widespread use and potential adverse effects in young developing organism, this study focused on the nephrotoxicity and genotoxicity of chronic low-dose exposure to silver nanoparticles (AgNPs) in 32 14-day-old male Wistar rats, randomly divided into three groups receiving AgNP solution (3 mg/kg body weight) intraperitoneally for one, two, or three weeks and the untreated control group (eight animals per group). When the rats were eight weeks old, blood creatinine and urine microalbumin were tested, followed by haematoxylin and eosin (H&E) staining. Proteinuria was found in the animals treated with AgNP for three weeks, and H&E staining revealed pathological changes in the kidney sections of this group. DNA damage was detected with the alkaline comet assay in the groups treated for two and three weeks. All results indicate that chronic exposure, even at a low dose, may affect animal health. The main culprit might be increased and time-dependent reactive oxygen species (ROS) production. Highly reactive ROS could cause a major structural damage to proteins and DNA, change the expression of ion channel proteins, and trigger inflammation. The findings of our in vivo experiment raise concern about nephrotoxic and genotoxic effects of silver nanoparticles in young organisms and call for further investigation of nanoparticle properties that can be modified to minimise the risks.
Keywords:alkaline comet assay   inflammation   oxidative stress   trpc6 cation channel
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