Inhaled silver nanoparticles induce pulmonary oxidative injury and inflammation: Differential effects between rat strains

Introduction: Silver nanoparticles (AgNP) have been reported to induce pulmonary inflammation and altered breathing rates in rodents however the mechanisms are poorly understood Methods: Male Sprague Dawley (SD) and Brown Norway (BN) rats n=5-12, were exposed by nose only inhalation to air or spark-generated 20nm AgNP (1.1 mg/m 3 ) for 3 hours on 1 or 4 consecutive days. Pulmonary deposition was estimated to be 0 (air only), 8, 12, or 40mg/rat using the Multiple Path Particle Dosimetry Model (MMAD). Results: Total BAL cell counts increased in rats at 24 hours, which consisted mostly of neutrophils (SD: 4.53 x10 6 ; BN: 2.71 x10 6 P 6 ; BN 1.19 x10 6 P>0.05). BN rats also had elevated eosinophils (1.33x10 6 P 0.05) with a similar trend for serum 8-OH-deoxyguanosine, the DNA oxidative marker. There were no changes in lung function in SD rats; conversely BN rats showed elevated airway resistance (Rn), (0.046 cmH 2 O.s/mL P 2 O.s/mL P 2 O/mL P>0.05) at 24hrs, indicating lung stiffness. Conclusions: AgNP inhalation induced transient oxidative injury and pulmonary inflammation that could lead to altered pulmonary mechanics in BN rats.