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Inhibitory effects of rosiglitazone on paraquat-induced acute lung injury in rats.
Acta Pharmacol Sin. 2013 Oct; 34(10):1317-24.AP

Abstract

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 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.

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-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.

CONCLUSION

Pretreatment with rosiglitazone protects rats against PQ-induced acute lung injury by activating PPAR-γ, inducing Nrf2 expression and inhibiting NF-κB activation.

Authors+Show Affiliations

Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23933652

Citation

Liu, Zhen-Ning, et al. "Inhibitory Effects of Rosiglitazone On Paraquat-induced Acute Lung Injury in Rats." Acta Pharmacologica Sinica, vol. 34, no. 10, 2013, pp. 1317-24.
Liu ZN, Zhao M, Zheng Q, et al. Inhibitory effects of rosiglitazone on paraquat-induced acute lung injury in rats. Acta Pharmacol Sin. 2013;34(10):1317-24.
Liu, Z. N., Zhao, M., Zheng, Q., Zhao, H. Y., Hou, W. J., & Bai, S. L. (2013). Inhibitory effects of rosiglitazone on paraquat-induced acute lung injury in rats. Acta Pharmacologica Sinica, 34(10), 1317-24. https://doi.org/10.1038/aps.2013.65
Liu ZN, et al. Inhibitory Effects of Rosiglitazone On Paraquat-induced Acute Lung Injury in Rats. Acta Pharmacol Sin. 2013;34(10):1317-24. PubMed PMID: 23933652.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory effects of rosiglitazone on paraquat-induced acute lung injury in rats. AU - Liu,Zhen-Ning, AU - Zhao,Min, AU - Zheng,Qiang, AU - Zhao,Hong-Yu, AU - Hou,Wei-Jian, AU - Bai,Shu-Ling, Y1 - 2013/08/12/ PY - 2012/11/06/received PY - 2013/04/18/accepted PY - 2013/8/13/entrez PY - 2013/8/13/pubmed PY - 2014/3/22/medline SP - 1317 EP - 24 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 34 IS - 10 N2 - 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 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. 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-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. CONCLUSION: Pretreatment with rosiglitazone protects rats against PQ-induced acute lung injury by activating PPAR-γ, inducing Nrf2 expression and inhibiting NF-κB activation. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/23933652/Inhibitory_effects_of_rosiglitazone_on_paraquat_induced_acute_lung_injury_in_rats_ L2 - https://doi.org/10.1038/aps.2013.65 DB - PRIME DP - Unbound Medicine ER -