Anti-inflammatory and antioxidant effect of cerium dioxide nanoparticles immobilized on the surface of silica nanoparticles in rat experimental pneumonia

Abstract

A massage with the potent counter-inflammatory material, cerium dioxide nanoparticles, is promising and the antioxidant properties of CeO2 are considered the main, if not the only, mechanism of this action. Nevertheless, the elimination of ceria nano-particles from the organism is very slow and there is a strong concern for toxic effect of ceria due to its accumulation. To overcome this problem, we engineered a combined material in which cerium nanoparticles were immobilized on the surface of silica nanoparticles (CeO2 NP), which is shown to be easily removed from an organism and could be used as carriers for nano-ceria. In our study particle size was 220±5nm, Zeta-potential −4.5mV (in water), surface charge density −17.22μC/cm2 (at pH 7).Thirty-six male Wistar rats, 5 months old and 250–290g were divided into four groups: 1) control; 2) CeO2 NP treatment; 3) experimental pneumonia (i/p LPS injection, 1mg/kg); and 4) experimental pneumonia treated with CeO2 NP (4 times during the study in dosage of 0.6mg/kg with an orogastric catheter). Gas exchange and pulmonary ventilation were measured four times: 0, 1, 3 and 24h after LPS injection in both untreated and CeO2 NP-treated animals. The mRNA of TNF-α, Il-6, and CxCL2 were determined by RT-PCR. ROS-generation in blood plasma and lung tissue homogenates were measured by means of lucigenin- and luminol-enhanced chemiluminescence.Endotoxemia in the acute phase was associated with: (1) pathological changes in lung morphology; (2) increase of ROS generation; (3) enhanced expression of CxCL2; and (4) a gradual decrease of VO2 and VE. CeO2 NP treatment of intact animals did not make any changes in all studied parameters except for a significant augmentation of VO2 and VE. CeO2 NP treatment of rats with pneumonia created positive changes in diminishing lung tissue injury, decreasing ROS generation in blood and lung tissue and decreasing pro-inflammatory cytokine expression (TNF-α, Il-6 and CxCL2). Oxygen consumption in this group was increased compared to the LPS pneumonia group.In our study we have shown anti-inflammatory and antioxidant effects of CeO2 NP. In addition, this paper is the first to report that CeO2 NP stimulates oxygen consumption in both healthy rats, and rats with pneumonia. We propose the key in understanding the mechanisms behind the phenomena lies in the property of CeO2 NP to scavenge ROS and the influence of this potent antioxidant on mitochondrial function. The study of biodistribution and elimination of СеО2NP is the purpose of our ongoing study.