Management of cardiovascular disease by cerium oxide nanoparticles via alleviating oxidative stress and adipokine abnormalities

Abstract

Abstract The current study aimed to evaluate the role of cerium oxide nanoparticles (C-1), a potent antioxidant, in the medication of cardiovascular disease in obese animal model. C-1 was prepared using a modified sonication sol-gel method. Thirty-two adult male rats were equally divided into 4 groups (n=8/each). The first (control) and second (obese) groups are not treated while the obese rats in the third and fourth groups were given 15 and 30 mg/kg C-1(IP), respectively, for 8 weeks. Parameters of insulin resistance, adipocyte hormones, inflammatory markers, lipid profile, cardiac enzymes and cardiac iron content (C-Fe) were estimated. Moreover, histological study and immunohistochemical stain for inducible nitric oxide synthase (INOS) for cardiac and aortic tissues were performed. The XRD patterns of C-1 showed narrow symmetric diffraction peaks. The particle diameters were calculated from the TEM histogram (21.09 nm) and the Debye-Scherrer Method (20.74 nm) which were very similar. Using the most intense peak ( $$28.47^{\circ }$$ 28 . 47 ∘ ), structural parameters were calculated including nano-crystallite size, Micro-strain, Lorentz factor, Thomson polarization parameter, and Lorentz polarization parameter. BET was used to calculate The total surface area (S $$_{T}$$ T ), and specific surface area (S $$_{BET}$$ BET ). The XPS survey spectrum of C-1 showed peaks for C-1s, O-1s and Ce-3d. The treatment of obese rats with C-1 led to a significant decrease in body weight, C-Fe , plasma leptin, tumor necrosis factor-alpha (TNF $$\alpha$$ α ), interleukin-6 (IL6), C-reactive protein (CRP), resistin, cholesterol, triglycerides, low-density lipoprotein (LDL), Troponin, Creatinine Kinase-MB (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA) in cardiac tissue or in plasma. Also, C-1 lowered plasma monocyte chemoattractant protein-1 (MCP-1), Epithelial Neutrophil-Activating Peptide (ENA-78), and insulin and glucose levels in obese rats. Furthermore, C-1 alleviated the increase of cardiac iNOS. Moreover, C-1 mitigated pathological changes of cardiac muscle and aorta observed in obese rats. On the other hand, C-1 enhanced adiponectin, cardiac glutathione (GSH) and superoxide dismutase (SOD) in obese rats. The effect of C-1 is dose-dependent ( 30 mg/kg of C-1 is more evident than 15 mg/kg). The modified synthesis method may lead to a smaller particle size than that reported in our previously reported work. The XRD patterns of C-1 indicate its cubic structure with space group F m -3 m (225) which was matched by code id 4343161 from COD. The Raman spectrum of C-1 indicates the absence of rearrangement oxygen atoms, the presence of oxygen in its fluorite lattice positions, and the oxygen vacancies in C-1 and the Ce vibration model (F2g). The presence of ten peaks in the high-resolution Ce-3d XP spectrum indicates the existence of both Ce3+ and Ce4+. C-1 showed therapeutic efficacy in atherosclerosis and cardiac muscle abnormalities associated with obese rats, probably because of their antioxidant and anti-inflammatory properties, which lead to lowering oxidative stress.

Keywords

• Cerium oxide nanoparticles
• Obesity
• Aorta
• Cardiac muscle
• Adipokines
• Oxidative stress