Abstract
Alpha-lipoic acid (ALA), occurring naturally in human food, is known to possess antioxidative and anti-inflammatory activities. Induction of heme oxygenase-1 (HO-1) has been reported to exhibit a therapeutic effect in several inflammatory diseases. The aim of study was to test the hypothesis that the protection of ALA against lipopolysaccharide-(LPS-) induced acute lung injury (ALI) is mediated by HO-1. Pre- or posttreatment with ALA significantly inhibited LPS-induced histological alterations of ALI, lung tissue edema, and production of proinflammatory cytokine, cytokine inducible neutrophil chemoattractant-3, and nitrite/nitrate in bronchoalveolar lavage fluid. In addition, the inflammatory responses including elevation of superoxide formation, myeloperoxidase activity, polymorphonuclear neutrophils infiltration, nitrotyrosine, inducible nitric oxide synthase expression and nuclear factor-kappa B (NF-κB) activation in lung tissues of LPS-instilled rats were also markedly reduced by ALA. Interestingly, treatment with ALA significantly increased nuclear factor-erythroid 2-related factor 2 (Nrf2) activation and HO-1 expression in lungs of ALI. However, blocking HO-1 activity by tin protoporphyrin IX (SnPP), an HO-1 inhibitor, markedly abolished these beneficial effects of ALA in LPS-induced ALI. These results suggest that the protection mechanism of ALA may be through HO-1 induction and in turn suppressing NF-κB-mediated inflammatory responses.
Highlights
Acute lung injury (ALI), a frequent critical complication in patients with sepsis or infection, has a high mortality rate of 30% to 40% despite advanced technique and support treatment used [1]
These results suggest that ALAmediated induction of heme oxygenase-1 (HO-1) may be through nuclear factor-erythroid 2-related factor 2 (Nrf2) activation
Intratracheal instillation of LPS resulted in a significant increase in protein level in Bronchoalveolar Lavage Fluid (BALF) and lung edema evidenced by elevation of lung wet/dry weight ratio
Summary
Acute lung injury (ALI), a frequent critical complication in patients with sepsis or infection, has a high mortality rate of 30% to 40% despite advanced technique and support treatment used [1]. Suppression of innate immune system-mediated inflammatory responses may be a potential strategy to attenuate the progression of ALI. Lipopolysaccharide (LPS), the major component of the utter membrane of Gram-negative bacteria, has been considered a key molecule triggering innate immunity and acute inflammatory responses through overproduction of proinflammatory cytokines, chemokines, reactive oxygen species (ROS), and nitric oxide (NO), and in turn resulting in ALI [3, 4]. Intratracheal administration of LPS into lungs may be an ideal experimental model of ALI, for it causes lung injury without resulting in systemic inflammation and multiorgan failure [6]
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