Abstract
To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage.
Highlights
The application of specific Cox-2 inhibitors can block this type of lung injury remains to be investigated.utilized a rat model of single-course paclitaxel chemotherapy, the primary objective of this study was to clarify the characteristics and mechanisms of paclitaxel chemotherapy-induced lung injury by detecting the alveolar-capillary barrier permeability, the expression of lung tissue inflammatory cytokines, and the levels of Cox-2 and tight junctions (TJs) proteins (Zo-1 and Claudin-4)
Experimental results showed the following: (1) the pathological sections of the paclitaxel chemotherapy group (Pac) group showed edema, exudation, and thickening of the alveolar septa, inflammatory cell infiltration, and small patches of red blood cells in alveolar cavity, suggesting that the inflammatory response was involved in the injury process and confirming the increased water and cell permeability of the alveolar-capillary membrane (ACM); (2) the Pac group of lung tissue showed increased Evans blue content and lung permeability index (LPI)
These two results suggested that the physical barrier and electrochemical barrier functions of ACM were damaged, leading to an increased permeability for macromolecules and charged molecules; (3) blood gas analysis results showed that the Pac group had increased PCO2 levels and decreased PO2 and SaO2 levels, which were significantly different from those of the control group (Con) group, indicating that paclitaxel damaged the ACM and thereby affected gas exchange
Summary
The application of specific Cox-2 inhibitors can block this type of lung injury remains to be investigated.utilized a rat model of single-course paclitaxel chemotherapy, the primary objective of this study was to clarify the characteristics and mechanisms of paclitaxel chemotherapy-induced lung injury by detecting the alveolar-capillary barrier permeability, the expression of lung tissue inflammatory cytokines, and the levels of Cox-2 and TJ proteins (Zo-1 and Claudin-4). The overarching goal of this study was to explorelung injury amelioration by the Cox-2-specific inhibitor parecoxib sodium, providing experimental evidence for the prevention and treatment of postoperative pulmonary complications in patients receiving neoadjuvant chemotherapy
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