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| Protective effect of TO901317 against paraquat-induced acute lung injury of mice |
| Hu Xiao, Jia Dong, Chen Liang-hong, Wang Yu, Zhao Min |
| Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China |
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Abstract Objective To investigate the effect and mechanism of TO901317, liver X receptors (LXRs) agonist, against paraquat (PQ)-induced acute lung injury. Methods A total of 96 c57 mice were randomly divided into 4 groups of 24 each. Control group: mice were intraperitoneally injected with 0.1 mL normal saline solution. PQ group: mice were intraperitoneally injected with PQ at a dose of 28 mg /kg. Low dose TO901317 group: mice were intraperitoneally injected with TO901317 at a dose of 5 mg/kg 30 min after PQ exposure. High dose TO901317 group: mice were intraperitoneally injected with TO901317 at a dose of 20 mg/kg 30 min after PQ exposure. At 6, 12, 24, and 72 h after PQ administration, 6 mice in each group were sacrificed to collect the lung tissues and bronchoalveolar lavage fluid (BALF) for testing. Histopathology changes of lung tissues were measured by HE staining. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities in lung tissues, TNF-α and IL-1β levels in BALF were respectively detected in each group. Nuclear factor-kappa B (NF-κB) expression in lung tissues were evaluated by Western blot. Results Compared with control group, PQ exposure induced severe lung tissue lesions (P＜0.05). PQ exposure also significantly increased the levels of MDA, TNF-α and IL-1β while decreased the activities of SOD (P＜0.05). Furthermore, PQ exposure markedly upregulated the expression of NF-κB in lung tissues (P＜0.05). In comparison with PQ group, TO901317 treatment significantly alleviated lung tissue lesions, decreased the levels of MDA, TNF-α and IL-1β, increased the activities of SOD, and downregulated the expression of NF-κB. Conclusion LXRs agonist TO901317 treatment significantly alleviates PQ-induced acute lung injury of mice by inhibition of NF-κB signaling pass way.
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Received: 21 March 2017
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Corresponding Authors:
Zhao Min, E-mail: zhaom@sj-hospital.org
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