Cardiotoxicity and lung toxicity in male rats induced by long-term exposure to iron oxide and silver nanoparticles

Mokhtar Ibrahim Yousef; Abdelsalam Abdalla Abuzreda; Maher Abdel-Nabi Kamel

doi:10.3892/etm.2019.8108

Cardiotoxicity and lung toxicity in male rats induced by long-term exposure to iron oxide and silver nanoparticles

Exp Ther Med. 2019 Dec;18(6):4329-4339. doi: 10.3892/etm.2019.8108. Epub 2019 Oct 16.

Authors

Mokhtar Ibrahim Yousef¹, Abdelsalam Abdalla Abuzreda¹, Maher Abdel-Nabi Kamel²

Affiliations

¹ Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria 21561, Egypt.
² Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt.

Abstract

Engineered nanoparticles (NPs) have been increasingly used in numerous fields over the last decade. In particular, iron oxide NPs (Fe₂O₃NPs) and silver NPs (AgNPs) have contributed to the current increase in NP usage. However, the possible side effects of increased NP exposure remain not fully elucidated. The present study aimed to assess the toxic effects of Fe₂O₃NPs and AgNPs, both individually and in combination, on the heart and lungs of male rats. To evaluate the in vivo NP toxic effects, the experimental animals were orally administered with Fe₂O₃NPs (5 mg/kg) and/or AgNPs (50 mg/kg). Animals were treated every day for 79 days. The results demonstrated that at the molecular level, Fe₂O₃NPs and AgNPs caused marked DNA base oxidation as indicated by the elevated DNA content of 8-hydroxy-2^-deoxyguanosine in the heart and lungs. Fe₂O₃NPs and/or AgNPs decreased paraoxonase 1, antioxidant enzymes, total antioxidant capacity, and reduced glutathione in heart and lung. A dose-dependent increase in production of creatine kinase, thiobarbituric acid-reactive substances, nitric oxide end products, tumor necrosis factor-α, interleukin-6 and lipid profiles was detected. Histological changes were also evident in heart and lung tissues. The two NPs demonstrated similar toxic effects for the majority of factors when co-supplemented. In conclusion, the present study identified that Fe₂O₃NPs and AgNPs, alone and in combination, induced cardiotoxicity and lung toxicity. Furthermore, findings demonstrated that there was a greater toxic effect due to administration of both NPs compared to individual administration. It was hypothesized that the toxic effects may be mediated through the induction of oxidative DNA damage, lipid peroxidation, shifting redox status, disrupted gene expression, and deregulation in cytokine production.

Keywords: 8-hydroxy-2′-deoxyguanosine; cardiotoxicity; cytokines; iron oxide nanoparticles; lung toxicity; oxidative stress; p53; silver nanoparticles.