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

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.

Effects of alpha lipoic acid on intra-abdominal adhesion: an experimental study in a rat model

“…[23] Low doses of intraperitoneal ALA was found to prevent intraabdominal adhesion due to the effects similar to those reported in the literature, [10][11][12][13] indicating the lack of a difference between low and high doses in terms of decreasing adhesion. Determining the lowest dose of ALA that is effective in preventing intraabdominal adhesions requires further studies.…”

“…However, no significant difference was seen in the necrosis rate between the groups. As Lin et al [13] has stated, it is possible to link the significant decrease in all microscopic vales evaluated to a reduction in the secretion of cytokines and anti-inflammatory effect of ALA.…”

“…Lin et al [13] have reported a decrease in edema and hyperemia, inflammation, fibrosis and alveolar wall thickness in acute lung trauma with the use of ALA. The author links this effect of ALA to the decreased release of the proinflammatory cytokines and its anti-inflammatory effect.…”

“…[6][7][8][9] The alpha-lipoic acid molecule is oxidized and converted to dihydrolipoic acid (DHLA) during the first contact of alphalipoic acid (ALA), an antioxidant substance, with free radicals. [10][11][12][13] Alpha lipoic acid also has anti-inflammatory effects and increases the levels of glutathione (GSH), tocopherol, and other natural antioxidants as ascorbic acid. It can indirectly affect the continuity of the cellular antioxidant defense.…”

“…[10] Due to its strong antioxidant nature, ALA has been reported to have positive effects in various pathological conditions such as diabetes, arteriosclerosis, neuron degeneration, multiple sclerosis, and joint diseases. [10,13] Özler et al [1] have reported that oral ALA reduces oxidative stress and has beneficial ef-…”