Cisplatin induces lung cell cilia disruption and lung damage via oxidative stress

Cisplatin (cis-diamminedichloroplatinum II) is widely used for the treatment of cancer, but its cellular toxicity, especially in the form of oxidative stress, limits its use in multiple organs including the lungs. As a cellular organelle, cilia play an important role in cellular function and can be damaged by oxidative stress. However, the effect of cisplatin-induced lung toxicity on cilia has not yet been defined. Herein, we investigated the association of cilia and oxidative stress with cisplatin-induced lung damage. Mice were administered with cisplatin. Some mice were treated with 2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito-TEMPO, a mitochondria-specific antioxidant) before the administration of cisplatin. Disruption of cilia was evaluated by the detection of ciliary proteins and fragments in the bronchoalveolar lavage fluid (BALF). Cisplatin caused the thickening of interalveolar septa, infiltration of immune cells into the interalveolar septa, and increased protein concentration and total cell number in the BALF. Cisplatin also increased ciliary fragments and proteins in the BALF. In the lungs, cisplatin increased the production of hydrogen peroxide, lipid peroxidation, and apoptosis, while decreasing manganese superoxide dismutase, isocitrate dehydrogenase 2, and catalase expression. Treatment with Mito-TEMPO prevented cisplatin-induced lung damage, ciliary fragmentation, oxidative stress, and apoptosis. By increasing oxidative stress in the lung, cisplatin induces lung cell damage, disruption of cilia, and release of disrupted cilia into the BALF. This suggests that cisplatin-induced lung damage can damage the cilia, manifesting as increased ciliary proteins in the BALF. •Cisplatin impairs redox balance in the lung.•Cisplatin causes oxidative stress in the lung tissue.•Cisplatin induces lung damage and cilia disruption.•Disrupted ciliary fragments are released into the bronchoalveolar lavage fluid.•Mito-TEPO treatment reduces cisplatin-induced lung damage and cilia disruption.