In vivo ameliorative effect of cerium oxide nanoparticles in isoproterenol-induced cardiac toxicity

Exp Toxicol Pathol. 2017 Sep 5;69(7):435-441. doi: 10.1016/j.etp.2017.03.001. Epub 2017 Apr 18.

Abstract

Background: Cerium oxide nanoparticles have gained much more attention especially in the field of nanomedicine. This work represents cerium oxide nanoparticles as a new prophylactic model for heart failure progression.

Objective: To investigate the potential protective effect of cerium oxide nanoparticles on Isoproterenol (ISO)-induced cardiac toxicity in rats.

Methods: Cerium oxide nanoparticles (5±1nm) were synthesized by reverse micelle method and characterized using High Resolution Transmission Electron Microscopy, X-Ray Diffraction and particle size analyzer. The experiments were performed on 96 male Wistar rats. The rats were randomly allocated into eight groups. Namely; two Negative and positive control groups, captopril administered group, Nano-ceria (low dose) group, Nano-ceria (high dose) group, Captopril- Isoproterenol group, Nano-ceria (low dose)-Isoproterenol group and Nano-ceria (high dose)-Isoproterenol group. Cardio toxic rat model was induced by subcutaneous administration of Isoproterenol (ISO) (30mg/kg) for two consecutive days in adult male rats. Two doses (0.5 and 5μg/kg/week) of cerium oxide nanoparticles were applied for five weeks and 50mg/kg/day of Captopril was used as a reference drug. Cardiac marker enzymes, Cortisol and Aldosterone hormones were assessed in serum. Oxidant-antioxidant parameters and histopathological examination in heart tissues were also determined.

Results: These dose of nano-ceria, showed a promising ameliorative and prophylactic effect against cardiac toxicity compared to Captopril reference drug. Serum cardiac markers were decreased by noticeable percentage, CK-MB (50% and 57%), LDH (47% and 57.7%), AST (38% and 36.5%) and ALT (33.5% and 30.6%) for both doses respectively, while increased tissues level of the antioxidant enzymes, catalase (48% - 26%) and superoxide dismutase (64%, 143%).

Conclusion: These consistent biochemical and histopathological results suggest that, nano-ceria could be used as effective antioxidant in prophylactic protocols for management of cardiac disorders associated with oxidative stress.

Keywords: Ameliorative effect; Antioxidant; Cardiac toxicity; Nano-ceria; Oxidative stress.

MeSH terms

  • Animals
  • Cardiotonic Agents / toxicity
  • Cerium / pharmacology*
  • Heart / drug effects*
  • Heart Failure* / chemically induced
  • Isoproterenol / toxicity
  • Male
  • Metal Nanoparticles*
  • Oxidative Stress / drug effects
  • Random Allocation
  • Rats
  • Rats, Wistar

Substances

  • Cardiotonic Agents
  • Cerium
  • ceric oxide
  • Isoproterenol