Inhibitory effects of rosiglitazone on paraquat-induced acute lung injury in rats.

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: Zhen-Ning Liu, Min Zhao, Qiang Zheng, Hong-Yu Zhao, Wei-Jian Hou, Shu-Ling Bai
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 34 Issue 10 Pg. 1317-24 (Oct 2013) ISSN: 1745-7254 [Electronic] United States
• PMID: 23933652 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Herbicides
• Interleukin-1beta
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, rat
• PPAR gamma
• Thiazolidinediones
• Tumor Necrosis Factor-alpha
• Rosiglitazone
• Malondialdehyde
• Superoxide Dismutase
• Paraquat

Topics

• Acute Lung Injury (chemically induced, physiopathology, prevention & control)
• Animals
• Dose-Response Relationship, Drug
• Herbicides (toxicity)
• Interleukin-1beta (blood)
• Male
• Malondialdehyde (blood)
• NF-E2-Related Factor 2 (genetics)
• NF-kappa B (metabolism)
• PPAR gamma (agonists)
• Paraquat (toxicity)
• Pulmonary Edema (physiopathology, prevention & control)
• Rats
• Rats, Sprague-Dawley
• Rosiglitazone
• Superoxide Dismutase (metabolism)
• Thiazolidinediones (administration & dosage, pharmacology)
• Time Factors
• Tumor Necrosis Factor-alpha (blood)