Effect of Ambient PM2.5 on Lung Mitochondrial Damage and Fusion/Fission Gene Expression in Rats

Exposure to ainbient fine particulate Matter (PM2.5) increases the risk of respiratory disease. Although previous mitochondria' research has provided new information about PM toxicity in the lung, the exact mechanism of PM2.5 mediated structural and functional damage of lung 'mitochondria remains unclear. In this study, changes in lung, mitochondria' morphology, expression of mitochondria' fission/fusion markers, lipid peroxidation, and transport ATPase activity in SD rats exposed to ambient PM2.5 at different dosages were investigated. Also, the release of reactive oxygen species -(ROS) via the respiratory burst in rat alveolar macrophages (AMs) exposed, to PM2.5 was examined by luminoldependent chemiluminescence (CL). The results showed that (1) PM2.5 deposited in the lung and induced pathological damage; particularly causing abnormal alterations ofinitochondrial structure, including mitochondria' swelling and,cristae disorder or,even fragmentation in the presence of higher doses of PM2.5; (2) PM2.5 significantly affected ected the expression-of specific Mitochondria fissiOn/fusion markers (OPA1,. Mfnl; Mfo2, Fi81, and Drpl) in rat lung; (3) PM2,5 inhibited Mn superoxide disinutase (MnSOD), Ner-ATPase, and Ca2+-ATPase activities and elevated malondialdehyde (MDA) content in rat lung mitochondria; and,(4) PM2.5 induced rat AMs to produce ROS, Which was inhibited by about 84.1% by diphenyleneiodbnium- chloride '(DPI), an important ROS generation inhibitors It is suggested that the pathological injury observed in rat lung exposed to PM2.5 is associated with mitochondrial fusion fission dysfunction, ROS -generation; mitochondrial lipid peroxidation,, and cellular homeostasis imbalance. Damage-to lung mitochondria may be one of the importantmechanisms by which PM2.5 induces lung injury, contributing to respiratory diseases.