Inhibitory effects of rosiglitazone on paraquatinduced acute lung injury in rats
查看参考文献37篇
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文摘
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Aim: To investigate the effects of the PPAR-γ agonist rosiglitazone on acute lung injury induced by the herbicide paraquat (PQ) and the underlying mechanisms of action. Methods: Male Sprague-Dawley rats were injected with PQ (20 mg/kg, ip). Rosiglitazone (3 or 10 mg/kg, ip) was administered I h before PQ exposure. Peripheral blood was collected at 4, 8, 24, and 72 h after PQ exposure for measuring the levels of MDA, TNF-a and IL-lβ, and the SOD activity. Lung tissues were collected at 72 h after PQ exposure to determine the wet-to-dry (W/D) ratios and lung injury scores, as well as the protein levels of NF-KBp65, PPAR-y, Nrf2, IkBα, and plKBa. Results: At 72 h after PQ exposure, the untreated rats showed a 100% cumulative mortality, whereas no death was observed in rosiglitazone-pretreated rats. Moreover, rosiglitazone pretreatment dose-dependently attenuated PQ-induced lung edema and lung histopathological changes. The pretreatment significantly reduced the levels of TNF-a, IL-lβ, and MDA, increased SOD activity in the peripheral blood of PQ-treated rats. The pretreatment also efficiently activated PPAR-y, induced Nrf2 expression and inhibited NF-kB activation in the lung tissues of PQ-treated rats. Furthermore, the pretreatment dose-dependently inhibited IkB-α degradation and phosphorylation, thus inhibiting NF-kB activation. Conclusion: Pretreatment with rosiglitazone protects rats against PQ-induced acute lung injury by activating PPAR-y, inducing Nrf2 expression and inhibiting NF-kB activation. |
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来源
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Acta Pharmacologica Sinica
,2013,34(10):1317-1324 【核心库】
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DOI
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10.1038/aps.2013.65
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关键词
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rosiglitazone
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herbicide
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paraquat
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acute lung injury
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PPAR-γ
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NF-kB
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Nrf2
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toxicity
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地址
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1.
Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004
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Department of Tissue Engineering, China Medical University, Shenyang, 110001
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语种
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英文 |
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文献类型
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研究性论文 |
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ISSN
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1671-4083 |
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学科
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药学 |
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基金
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国家自然科学基金
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文献收藏号
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CSCD:4935195
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37
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