Ethyl gallate attenuates acute lung injury through Nrf2 signaling

Mehla, Kamiya ; Balwani, Sakshi ; Agrawal, Anurag ; Ghosh, Balaram (2013) Ethyl gallate attenuates acute lung injury through Nrf2 signaling Biochimie, 95 (12). pp. 2404-2414. ISSN 0300-9084

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Official URL: http://doi.org/10.1016/j.biochi.2013.08.030

Related URL: http://dx.doi.org/10.1016/j.biochi.2013.08.030

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.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:LPS; Inflammation; Monocytes; Antioxidants; Nrf2.
ID Code:120959
Deposited On:08 Jul 2021 05:47
Last Modified:08 Jul 2021 05:47

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