5‑Aminosalicylic acid attenuates paraquat‑induced lung fibroblast activation and pulmonary fibrosis of rats.

Abstract

Pulmonary fibrosis is one of the most important pathological processes associated with paraquat (PQ) poisoning. 5‑Aminosalicylic acid (5‑ASA) has been shown to be a promising agent against fibrotic diseases. In the present study, the alleviating role of 5‑ASA was evaluated in a rat model of pulmonary fibrosis induced by PQ intragastric poisoning (80mg/kg). Wistar rats were divided into control, PQ, 5‑ASA (30mg/kg daily, 14days) and PQ + 5‑ASA groups. Histological examination revealed congestion, edema and inflammatory cell infiltration in the bronchial and alveolar walls at3days after PQ exposure. Alveolar septum thickening with alveolar lumen narrowing was observed at14days, while fibroblast proliferation, increase in collagen fiber number and fibrous thickening of the alveolar walls were observed at28day. All the aforementioned pulmonary injury changes in the PQ group were attenuated in the PQ + 5‑ASA group. Hydroxyproline (HYP) content increased in the lung tissues of the rats at14days after PQ treatment and reached a peak at28days. Compared with the PQ group, HYP contents of lung tissue decreased at14and28days after PQ + 5‑ASA treatment. Masson's trichrome staining revealed that the increase in the amount of collagen fibers in the lung tissues of rats in the PQ group was inhibited by 5‑ASA treatment, further confirming the alleviating effect of 5‑ASA on fibrosis. In addition, the results showed that 5‑ASA attenuated the upregulation of transforming growth factor‑β1 and phosphorylated‑SMAD3, and the reduction of peroxisome proliferator activated receptor γ induced by PQ in lung tissue of rats and human lung fibroblast WI‑38 VA13 cells. In conclusion, the results suggested that 5‑ASA had an alleviating effect on PQ‑induced pulmonary fibrosis, partly by suppressing the activation of the TGF‑β1 signaling pathway.