Protective Effect of Nicotine on Lipopolysaccharide-Induced Acute Lung Injury in Mice

Abstract

Background: Recently, nicotine administration has been shown to be a potent inhibitor of a variety of innate immune responses, including endotoxin-induced sepsis. Objective: It was the aim of this study to evaluate the effect of nicotine on attenuating lung injury and improving the survival in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: ALI was induced in mice by intratracheal instillation of LPS (3 mg/ml). The mice received intratracheal instillation of nicotine (50, 250 and 500 µg/kg) before or after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain, and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and high mobility group box (HMGB)-1, as well as myeloperoxidase (MPO) activity were measured by enzyme-linked immunosorbent assay. The mortality rate was recorded and analyzed by the Kaplan-Meier method. Results: Nicotine pretreatment significantly attenuated the severity of lung injury and inhibited the production of TNF-α, IL-1β and HMGB-1 in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by nicotine pretreatment. Early treatment with a high dose of nicotine (500 µg/kg) after LPS administration decreased the mortality in mice with ALI, even when treatment was started 24 h after LPS administration. Conclusion: Nicotine attenuated the lung injury and reduced mortality in mice with LPS-induced ALI.

Tanshinone II is a potent candidate for treatment of lipopolysaccharide-induced acute lung injury in rat model

“…In the present study, the effect of tanshinone II on ALI in an LPS-induced lung injury rat model was analyzed. Administration of LPS induces cellular inflammatory processes and subsequent pulmonary injury in animals (22,23). The present results demonstrated that LPS administration enhanced the concentration of proteins in pulmonary fluid of rats.…”

Auricularia auricular-judae polysaccharide attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress and inflammation

“…LPS is a principal component of the outer membrane of Gram-negative bacteria and can enter the blood stream and elicit inflammatory responses that may lead to shock and ultimately to death (20). LPS-induced lung injury in the rat is frequently used as a model for studying ALI (21). Thus, this model was used in the present study to investigate the prevention of AAP on LPS-induced ALI in mice.…”

Treatment of Acute Lung Injury: Time to Think Outside the Box?

“…In vivo, nicotine improved survival in septic animal models, even if nicotine was given after the onset of sepsis [10] . The paper by Ni et al [11] in this issue of Respiration confirmed this sentinel observation, supporting the concept that targeting the 'late-phase' inflammatory response opens up novel options for the management of ALI. They showed reduced lung damage, neutrophil recruitment into the lung, cytokine production and survival even if the nicotine was given 24 h after the injurious insult.…”

“…A key issue is whether the inciting trigger for ALI determines the response to blocking ␣ 7nAChR, highlighted by the contrasting results from the instilling lipopolysaccharide in the lung [10,11] to ALI induced by the systemic effects of the remote infection [14] . In general, ALI induced by triggers such as trauma and acid aspiration has better outcomes than ALI triggered by systemic infection or sepsis.…”