Inhibitory effects of rosiglitazone on paraquat-induced acute lung injury in rats
| Autor: | Wei-jian Hou, Zhenning Liu, Shu-ling Bai, Hongyu Zhao, Min Zhao, Qiang Zheng |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Paraquat Agonist Time Factors NF-E2-Related Factor 2 medicine.drug_class Acute Lung Injury Interleukin-1beta Pulmonary Edema Lung injury Pharmacology Rats Sprague-Dawley Rosiglitazone chemistry.chemical_compound Malondialdehyde medicine Animals Pharmacology (medical) Dose-Response Relationship Drug Herbicides Superoxide Dismutase Tumor Necrosis Factor-alpha business.industry NF-kappa B General Medicine Pulmonary edema medicine.disease Rats PPAR gamma IκBα Dose–response relationship chemistry Anesthesia Original Article Thiazolidinediones business medicine.drug |
| Zdroj: | Acta Pharmacologica Sinica. 34:1317-1324 |
| ISSN: | 1745-7254 1671-4083 |
| DOI: | 10.1038/aps.2013.65 |
| Popis: | 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. Male Sprague-Dawley rats were injected with PQ (20 mg/kg, ip). Rosiglitazone (3 or 10 mg/kg, ip) was administered 1 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-α and IL-1β, 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-κBp65, PPAR-γ, Nrf2, IκBα and pIκBα. 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-α, IL-1β and MDA, increased SOD activity in the peripheral blood of PQ-treated rats. The pretreatment also efficiently activated PPAR-γ, induced Nrf2 expression and inhibited NF-κB activation in the lung tissues of PQ-treated rats. Furthermore, the pretreatment dose-dependently inhibited IκB-α degradation and phosphorylation, thus inhibiting NF-κB activation. Pretreatment with rosiglitazone protects rats against PQ-induced acute lung injury by activating PPAR-γ, inducing Nrf2 expression and inhibiting NF-κB activation. |
| Databáze: | OpenAIRE |
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