Impact of zinc oxide nanoparticles on thioredoxin-interacting protein and asymmetric dimethylarginine as biochemical indicators of cardiovascular disorders in gamma-irradiated rats

Environ Toxicol. 2020 Apr;35(4):430-442. doi: 10.1002/tox.22879. Epub 2019 Nov 21.

Abstract

Nanoparticle is a microscopic particle that has been existed in a wide range of biotechnological purposes. Zinc oxide nanoparticles (ZnO-NPs) have fewer environmental hazards and have shown positive impacts in the medical field. This work aimed to observe the effects of low and high doses of ZnO-NPs on heart injury induced by ionizing radiation (IR). Animals were irradiated by 8 Gy of gamma rays and ZnO-NPs (10 and 300 mg/Kg/day) were orally delivered to rats 1 hour after irradiation. Animals were dissected on 15th day postirradiation. Data showed that the oxidative damage resulted from radiation exposure, appeared by marked increments in the malondialdehyde (MDA) content and the level and protein expression of thioredoxin-interacting protein (TXNIP) with a noticeable decline in the level and expression of thioredoxin 1 (Trx-1) and thioredoxin reductase (TrxR), as well as glutathione (GSH) level and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Moreover, radiation-induced inflammation, manifested by a noticeable elevation in the level of tumor necrotic factor-alpha (TNF-α), interleukin-18 (IL-18), and C-reactive protein (CRP). Additionally, endothelial dysfunction marked with a high level of asymmetric dimethylarginine (ADMA), total nitrite/nitrate (NOx), intercellular adhesion molecule 1 (ICAM-1), homocysteine (Hcy), creatine kinase (CK-MB), cardiac troponin-I (cTn-I), and lactate dehydrogenase (LDH). In addition, a decrease of zinc (Zn) level in the cardiac tissue was recorded. ZnO-NPs treatment (10 mg/kg) mitigated the oxidative stress and inflammation effects on the cardiovascular tissue through the positive modulations in the studied parameters. In contrast, ZnO-NPs treatment (300 mg/kg) induced cardiovascular toxicity of normal rats and elevated the deleterious effects of radiation. In conclusion, ZnO-NPs at a low dose could mitigate the adverse effects on cardiovascular tissue induced by radiation during its applications, while the high dose showed morbidity and mortality in normal and irradiated rats.

Keywords: Zn oxide; asymmetric dimethylarginine; nanoparticles; radiation; rats; thioredoxin-interacting protein.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Biomarkers / metabolism
  • Cardiotoxicity
  • Cell Cycle Proteins / metabolism*
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Gamma Rays*
  • Heart* / drug effects
  • Heart* / radiation effects
  • Inflammation
  • Male
  • Nanoparticles / chemistry*
  • Oxidative Stress / drug effects
  • Radiation Injuries, Experimental / immunology
  • Radiation Injuries, Experimental / metabolism*
  • Radiation Injuries, Experimental / prevention & control
  • Rats
  • Zinc Oxide / chemistry
  • Zinc Oxide / pharmacology*
  • Zinc Oxide / toxicity

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • Cytokines
  • TXNIP protein, rat
  • N,N-dimethylarginine
  • Arginine
  • Zinc Oxide