Pulmonary exposure to silver nanoparticles impairs cardiovascular homeostasis: Effects of coating, dose and time

Zannatul Ferdous, Suhail Al-Salam, Yaser E. Greish, Badreldin Ali, Abderrahim Nemmar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Pulmonary exposure to silver nanoparticles (AgNPs) revealed the potential of nanoparticles to cause pulmonary toxicity, cross the alveolar-capillary barrier, and distribute to remote organs. However, the mechanism underlying the effects of AgNPs on the cardiovascular system remains unclear. Hence, we investigated the cardiovascular mechanisms of pulmonary exposure to AgNPs (10 nm) with varying coatings [polyvinylpyrrolidone (PVP) and citrate (CT)], concentrations (0.05, 0.5 and 5 mg/kg body weight), and time points (1 and 7 days) in BALB/C mice. Silver ions (Ag+) were used as ionic control. Exposure to AgNPs induced lung inflammation. In heart, tumor necrosis factor α interleukin 6, total antioxidants, reduced glutathione and 8-isoprostane significantly increased for both AgNPs. Moreover, AgNPs caused oxidative DNA damage and apoptosis in the heart. The plasma concentration of fibrinogen, plasminogen activation inhibitor-1 and brain natriuretic peptide were significantly increased for both coating AgNPs. Likewise, the prothrombin time and activated partial thromboplastin time were significantly decreased. Additionally, the PVP- and CT- AgNPs induced a significant dose-dependent increase in thrombotic occlusion time in cerebral microvessels at both time points. In vitro study on mice whole blood exhibited significant platelet aggregation for both particle types. Compared with AgNPs, Ag+ increased thrombogenicity and markers of oxidative stress, but did not induce either DNA damage or apoptosis in the heart. In conclusion, pulmonary exposure to AgNPs caused cardiac oxidative stress, DNA damage and apoptosis, alteration of coagulation markers and thrombosis. Our findings provide a novel mechanistic insight into the cardiovascular pathophysiological effects of lung exposure to AgNPs.

Original languageEnglish
Pages (from-to)36-50
Number of pages15
JournalToxicology and Applied Pharmacology
Publication statusPublished - Mar 15 2019


  • apoptosis
  • coating, thrombosis
  • DNA oxidative damage
  • Silver nanoparticles

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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