The Protective Effect of Alpha-Lipoic Acid in Lipopolysaccharide-Induced Acute Lung Injury Is Mediated by Heme Oxygenase-1

Abstract EN

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.