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

Aim: To investigate the effects of the PPAR-gamma 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-alpha and IL-1 beta, 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-kappa Bp65, PPAR-gamma, Nrf2, I kappa B alpha, and pI kappa B alpha. 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-alpha, IL-1 beta, and MDA, increased SOD activity in the peripheral blood of PQ-treated rats. The pretreatment also efficiently activated PPAR-gamma, induced Nrf2 expression and inhibited NF-kappa B activation in the lung tissues of PQ-treated rats. Furthermore, the pretreatment dose-dependently inhibited I kappa B-alpha degradation and phosphorylation, thus inhibiting NF-kappa B activation. Conclusion: Pretreatment with rosiglitazone protects rats against PQ-induced acute lung injury by activating PPAR-gamma, inducing Nrf2 expression and inhibiting NF-kappa B activation.