Abstract
This study mainly studied the effect of inhibition of nuclear factor-κB (NF-κB) signal by pyrrolidine dithiocarbamate (PDTC) on lipopolysaccharide (LPS)-induced inflammatory response, oxidative stress, and mitochondrial dysfunction in a murine acute lung injury model. The results showed that LPS exposure activated NF-κB and its upstream proteins and caused lung inflammation, oxidative stress, and mitochondrial dysfunction in mice. While inhibition of NF-κB by PDTC adminstration alleviated LPS-induced generation of lymphocytes, IL-1β, and TNF-α. Malondialdehyde, a common oxidative product, was markedly reduced after PDTC treatment in LPS-challenged mice. Furthermore, PDTC alleviated LPS-induced mitochondrial dysfunction via improving ATP synthesis and uncoupling protein 2 expression. In conclusion, inhibition of NF-κB by PDTC alleviated LPS-induced acute lung injury via maintaining inflammatory status, oxidative balance, and mitochondrial function in mice.
Highlights
Acute lung injury is a major causes of acute respiratory failure characterized by oxidative stress, inflammatory response, neutrophil accumulation, diffuse endothelium and epithelial damage, air-blood barrier disruption, and the subsequent infiltration of peripheral inflammatory cells into lung tissues [1, 2]
This study mainly studied the effect of inhibition of nuclear factor-κB (NF-κB) signal by pyrrolidine dithiocarbamate (PDTC) on lipopolysaccharide (LPS)-induced inflammatory response, oxidative stress, and mitochondrial dysfunction in a murine acute lung injury model
NF-κB activity was tested using ELISA kit and the results showed that LPS activated NF-κB signal (p < 0.05), suggesting that NF-κB involved in LPSinduced acute lung injury
Summary
Acute lung injury is a major causes of acute respiratory failure characterized by oxidative stress, inflammatory response, neutrophil accumulation, diffuse endothelium and epithelial damage, air-blood barrier disruption, and the subsequent infiltration of peripheral inflammatory cells into lung tissues [1, 2]. In the acute lung injury, NFκB has been widely served as the therapeutic target to alleviate inflammation. Acteoside, tylvalosin, and emodin were demonstrated to inhibit NF-κB signal, which further alleviated inflammatory response in acute lung injury models [3,4,5]. Small interfering RNA (siRNA) against NF-κB confirmed the beneficial effects of NF-κB inhibition on inflammatory response, including acute lung injury model [6]. Inhibition of the NFκB pathway considers as a potential strategy for the therapeutic target of this crucial transcription factor of acute lung injury. We used PDTC to inhibit NF-κB pathway to investigate the protective effects of NFκB inactivation by PDTC on lipopolysaccharide (LPS)induced acute lung injury in mice
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