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Evaluation of the toxicity effects of silk fibroin on human lymphocytes and monocytes
Authors:Parvaneh Naserzadeh  Seyed Alireza Mortazavi  Khadijeh Ashtari  Ahmad Salimi  Mehdi Farokhi  Jalal Pourahmad
Affiliation:1. Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Pharmaceutics School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran;3. Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran;4. Department of Medical Nanotechnology, Faculty of Advanced Technology in Medicine, Iran University of Medical Sciences, Tehran, Iran;5. Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran;6. National Cell Bank of Iran, Pasteur Institute of Iran, Iran;7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:Silk fibroin nanoparticles (SFNPs) as a natural polymer have been utilized in biomedical applications such as suture, tissue engineering‐based scaffolds, and drug delivery carriers. Since there is little data regarding the toxicity effects on different cells and tissues, we aimed to determine the toxicity mechanisms of SFNPs on human lymphocytes and monocytes based on reliable methods. Our results showed that SFNPs (0.5, 1, and 2 mg/mL) induced oxidative stress via increasing reactive oxygen species production, mitochondrial membrane potential (?Ψ) collapse, which was correlated to cytochrome c release and Adenosine diphosphate (ADP)/Adenosine tri phosphate (ATP) ratio increase as well as lysosomal as another toxicity mechanism, which led to cytosolic release of lysosomal digestive proteases, phosphor lipases, and apoptosis signaling. Taken together, these data suggested that SFNPs toxicity was associated with mutual mitochondrial/lysosomal cross‐talk and oxidative stress on human lymphocytes and monocytes with activated apoptosis signaling.
Keywords:lysosomal damage  membrane potential collapse  ROS formation  silk fibroin nanoparticles
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