Valproic Acid Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

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-kappa B) p65, nitric oxide, and inducible nitric oxide synthase in the lung tissues and the decreased levels of tumor necrosis factor alpha and interleukin-1 beta 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-kappa B activation probably through a mechanism depending on HDAC3 redistribution.