Influence of Nanoparticle Inhalation on Cardiac Mitochondrial Function

Abstract

Particle inhalation affects directly contacted tissues. Nanoparticles may elicit more robust effects due to their greater surface area. However, the effects to extrapulmonary tissues, such as the heart, are unclear. Mitochondria play a critical role in cardiac function and may be negatively influenced by particulate exposure. Cardiac mitochondria are situated in a spatially distinct manner, with those between the myofibrils (IFM) and those beneath the sarcolemma (SSM). The goal of this study was to determine the effect of titanium dioxide (nano‐TiO2) inhalation on mitochondrial function. Sprague‐Dawley rats were exposed to nano‐TiO2 aerosols (CMAD=140–150 nm) at 4–5 mg/m3; for 4–6 hrs to achieve a pulmonary deposition of 30 ìg/rat. Twenty‐four hours later, echocardiography revealed a decrease in cardiac ejection fraction. Mitochondrial functional analyses indicated a decrease in electron transport chain complex III, IV, and V activities, with the IFM most affected (P<0.05, for all three). Lipid peroxidation and protein carbonyl contents were increased in exposed IFM, as compared to control. Caspase 3 and 9 activities were increased in exposed hearts with no effect on caspase 8 activity. The results suggest that nanoparticle inhalation is associated with cardiac mitochondrial damage which may be subject to subcellular spatial influence.(Support: NIH DP2DK083095, 5T32HL090610, ES015022, ES018274)