Potential Application of Cerium Dioxide Nanoparticles for Acute Pneumonia Treatment

Cerium dioxide nanoparticles (CeO2 NP) have antioxidant properties and also can alter membrane potential in mitochondria influencing cell respiration. In this study we check the idea that CeO2 NP adsorbed on the silicon base has counter inflammatory, antioxidant and metabolic effects and can be possibly applied in pneumonia treatment. Thirty-six Wistar male rats, 5 months old, 250-290 g were divided in five groups: 1) intact animals; 2) i/p saline injection; 3) CeO2 NP treatment; 4) experimental pneumonia (i/p LPS injection, 1 mg/kg); 5) experimental pneumonia treated by CeO2 NP (2.5 mg/kg). Pulmonary ventilation and gas exchange were measured four times: before and 1, 3 and 24 h after LPS injection. The mRNA of TNF-α, Il-6, and CxCL3 were determined by RT-PCR. ROS-generation in blood plasma and lung tissue homogenate was measured by means of lucigenin- and luminol-enhanced chemiluminescence. Endotoxaemia in the acute phase was associated with essential inhibition of metabolism: gradual decrease of VE (by 72%) and VO2 (by 62%) 24 hour after LPS injection; pathological changes in lung morphology; enhanced expression of CxCL3 (by 68%); increase of ROS generation in blood (by 660%) and lungs (in 33%). LPS-injected rats treated with CeO2 NP did not demonstrate any VE and VO2 reduction 1 hour after LPS-injection and increase of VE (by 25%) and VO2 (by 20%) 3 hours after injection; this effect remained 24 hours after injection. It should be noted that CeO2 NP treatment of control rats increased VE by 20% and VO2 by 45% in comparison with first measurement after each introduction of the substance. Treatment of LPS-injected rats with CeO2 NP has led to diminishing in lung morphology pathological deviations; significant decrease of the expression of inflammatory markers: CxCL33 (in 7.1 times, p < 0.01), Il-6 (in 3.5 times, p < 0.05) and TNF-α (in 2 times, p = 0.05); significant reducing of ROS generation in blood (in 2.7 times, p < 0.05), and lung tissue homogenate (in 1.3 times p < 0.05). CeO2 NP significantly reduces morphological and functional pulmonary damage in course of experimental acute pneumonia. Discussing mechanism of this effect we propose two suggestions. First: CeO2 NP is powerful antioxidant, which protects lung tissue and, possibly, inhibits synthesis of cytokines. Second: treatment with CeO2 NP significantly accelerate metabolism and gives additional vigor to cells suffering with pneumonia.