• Shock · May 2017

    Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice.

    • Yong Zhou, Tian Liu, Jia-Xi Duan, Ping Li, Guo-Ying Sun, Yong-Ping Liu, Jun Zhang, Liang Dong, LeeKin Sing StephenKSS, Bruce D Hammock, Jian-Xin Jiang, and Cha-Xiang Guan.
    • *Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China †Department of Physiology, Hunan University of Medicine, Huaihua, Hunan China ‡Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou China §Department of Entomology and the UC Davis Cancer Center, University of California Davis, Davis, California ||State Key Laboratory of Trauma, Burns, and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, Sichuan, China.
    • Shock. 2017 May 1; 47 (5): 638-645.

    AbstractAcute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid with antihypertensive, profibrinolytic, and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols. The aim of this study was to investigate the role of sEH inhibitor trifluoromethoxyphenyl propionylpiperidin urea (TPPU) and EETs in lipopolysaccharide (LPS)-induced ALI of mice. Our studies revealed that inhibition of sEH with TPPU attenuated the morphological changes in mice, decreased the neutrophil infiltration to the lung, pro-inflammatory cytokine levels (IL-1β and TNF-α) in serum and bronchoalveolar lavage fluid (BALF), and alveolar capillary leakage (lung wet/dry ratio and total protein concentration in BALF). TPPU improved the survival rate of LPS-induced ALI. In addition, in vitro experiments revealed that both TPPU and EETs (11,12-EET and 14,15-EET) suppressed the expression of IL-1β and TNF-α, and LDH release in RAW264.7 cells. These results indicate that EETs play a role in dampening LPS-induced acute lung inflammation, and suggest that sEH could be a valuable candidate for the treatment of ALI.

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