Protective effect of adiponectin on paraquat-induced pulmonary fibrosis in mice

Abstract

Pulmonary fibrosis (PF) is the most common complication of paraquat (PQ) toxicity, which lacks an effective treatment. This study aimed to investigate whether exogenous administration of globular adiponectin (APN) isoform provided protection against PQ-induced PF, and examined the possible mechanisms underlying these effects. Eighty BALB/C mice were randomly divided into control, PQ, low-dose APN, and high-dose APN groups. Human lung WI-38 fibroblasts were similarly divided into control, PQ, and APN groups and examined at 24 h, 48 h, and 72 h after PQ exposure. Hematoxylin and eosin (HE) and Masson trichrome staining were used to compare the histopathologic changes in the mouse lung tissues. Western blot and real-time quantitative-PCR (RT-PCR) were used to measure the protein and mRNA expression of transforming growth factor β1 (TGF-β1) in mice lung tissues and α-SMA, type III collagen, and NF-κB p65 in lung fibroblasts. Dihydroethidium (DHE) was used to detect intracellular superoxide anion (O2 −) in fibroblasts. APN administration significantly ameliorated PQ-mediated fibrosis histologically and reduced the protein and mRNA expression levels of TGF-β1 in mouse lung tissues in a dose-dependent manner (P<0.05). When fibroblasts were pretreated with APN, the expression of aα-SMA and NF-κB p65 were down-regulated, and O2 − decreased. Expression of the anti-inflammatory factor IL-1Ra was upregulated following PQ exposure (P<0.05). This study revealed which may have occurred through suppression of NF-κB dependent inflammatory and TGF-β1 mediated fibrotic events.