Rosiglitazone attenuates paraquat-induced lung fibrosis in rats in a PPAR gamma-dependent manner

Abstract

Rosiglitazone, a PPAR-γ agonist, possesses anti-fibritic effect; however, its inhibitory effect on paraquat (PQ)-induced pulmonary fibrosis is not completely understood. Here, we investigated the inhibitory effect of rosiglitazone on PQ-induced acute pulmonary fibrosis in rats and its underlying mechanism. Male Sprague-Dawly rats were administered a single intraperitoneal injection of 30 mg/kg PQ and euthanised 7, 14, 21, and 28 days after PQ poisoning. PQ-induced pulmonary fibrosis was most obvious on day 28. Male Sprague-Dawly rats were exposed either against distilled water as control groups or PQ (30 mg/kg, i.p.) as test groups. The control groups were nominated as NC group (without treatment), RSG group (only treatment with rosiglitazone, 10 mg/kg/d), and GW group (only treatment with GW9662, a PPAR-γ antagonist, 1 mg/kg/d). The test groups were nominated as PQ group (PQ exposed without treatment), PQ + RSG group (treatment with rosiglitazone), and PQ + RSG + GW group (treatment with rosiglitazone and GW9662). Rosiglitazone was able to recover the PQ-induced decrease in arterial oxygen partial pressure (PaO2), increase in the wet-to-dry (W/D) lung tissue weight ratio and lung fibrosis score. Rosiglitazone inhibited the PQ-induced reduction in protein and mRNA levels of PPAR-γ and PTEN and elevation in protein and mRNA levels of TGF-β1 and α-SMA. GW9662 administration antagonized the effect of rosiglitazone. These data suggest that rosiglitazone attenuated PQ-induced pulmonary fibrosis by upregulateing PTEN and downregulating TGF-β1 expression in a PPAR-γ dependent manner.