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Cisplatin induces lung cell cilia disruption and lung damage via oxidative stress
- Source :
- Free Radical Biology and Medicine. 177:270-277
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Background 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. Methods 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). Results 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. Conclusion 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.
- Subjects :
- medicine.disease_cause
Biochemistry
Antioxidants
Lipid peroxidation
Mice
chemistry.chemical_compound
Physiology (medical)
medicine
Animals
Cilia
Lung
Cell damage
Cisplatin
medicine.diagnostic_test
biology
Chemistry
respiratory system
medicine.disease
respiratory tract diseases
Cell biology
Oxidative Stress
medicine.anatomical_structure
Bronchoalveolar lavage
Catalase
Apoptosis
biology.protein
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 177
- Database :
- OpenAIRE
- Journal :
- Free Radical Biology and Medicine
- Accession number :
- edsair.doi.dedup.....9f571de003f4fade2e2111ec920ef2f2
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2021.10.032