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Valproic Acid Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

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Abstract

Valproic acid (VPA) has been shown to exert anti-inflammatory and antioxidant effects in a range of diseases including septic shock. However, the effects of VPA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. We found that VPA pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the downregulated nuclear factor kappa B (NF-κB) p65, nitric oxide, and inducible nitric oxide synthase in the lung tissues and the decreased levels of tumor necrosis factor alpha and interleukin-1β in the bronchoalveolar lavage fluid. Furthermore, VPA reduced the nuclear histone deacetylase (HDAC)3 expression whereas increased the cytoplasmic HDAC3 expression. Our results suggested that VPA attenuates the LPS-induced ALI via inhibiting the NF-κB activation probably through a mechanism depending on HDAC3 redistribution.

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Acknowledgments

This work was supported by the Natural Science Foundation of Jiangsu Province (BK2012778).

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The authors have no potential conflicts of interest to disclose.

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Correspondence to Jian-jun Yang.

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Mu-huo Ji and Guo-min Li contributed equally to this work.

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Ji, Mh., Li, Gm., Jia, M. et al. Valproic Acid Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice. Inflammation 36, 1453–1459 (2013). https://doi.org/10.1007/s10753-013-9686-z

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  • DOI: https://doi.org/10.1007/s10753-013-9686-z

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