title: Ethyl gallate attenuates acute lung injury through Nrf2 signaling.
abstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is the clinical syndrome of persistent lung inflammation caused by various direct and indirect stimuli. Despite advances in the understanding of disease pathogenesis, few therapeutic have emerged for ALI/ARDS. Thus, in the present study we evaluated the therapeutic potential of ethyl gallate (EG), a plant flavanoid in the context of ALI using in vivo (BALB/c) and in vitro models (human monocytes). Our in vivo data supports the view that EG alleviates inflammatory condition in ALI as significant reduction in BALF neutrophils, ROS, proinflammatory cytokines and albumin levels were observed with the single i.p of EG post LPS exposure. Also, histochemical analysis of mice lung tissue demonstrated that EG restored LPS stimulated cellular influx inside the lung airspaces. Unraveling the mechanism of action, our RT-PCR and western blot analysis suggest that enhanced expression of HO-1 underlies the protective effect of EG on ROS level in mice lung tissue. Induction of HO-1 in turn appears to be mediated by Nrf2 nuclear translocation and consequent activation and ablation of Nrf2 activity through siRNA notably abrogated the EG induced protective effect in LPS induced human monocytes. Furthermore, our results indicate that EG generated moderate amounts of H2O2 could induce Nrf2 translocation in the in vitro systems. However, given the insignificant amount of H2O2 recorded in the injected material in the in vivo system, additional mechanism for EG action could not be excluded. Nevertheless our results highlight the protective role of EG in ALI and provide the novel insight into its usefulness as a therapeutic tool for the treatment of ALI.
authors.affiliation: Molecular Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
authors.forename: Kamiya
authors.initials: K
authors.lastname: Mehla
authors.forename: Sakshi
authors.initials: S
authors.lastname: Balwani
authors.forename: Anurag
authors.initials: A
authors.lastname: Agrawal
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C048734:ethyl gallate; D005707:Gallic Acid; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Antioxidants; Inflammation; LPS; Monocytes; Nrf2