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 (80 mg/kg). Wistar rats were divided into control, PQ, 5‑ASA (30 mg/kg daily, 14 days) and PQ + 5‑ASA groups. Histological examination revealed congestion, edema and inflammatory cell infiltration in the bronchial and alveolar walls at 3 days after PQ exposure. Alveolar septum thickening with alveolar lumen narrowing was observed at 14 days, while fibroblast proliferation, increase in collagen fiber number and fibrous thickening of the alveolar walls were observed at 28 day. 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 at 14 days after PQ treatment and reached a peak at 28 days. Compared with the PQ group, HYP contents of lung tissue decreased at 14 and 28 days 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.
Keywords: 5‑Aminosalicylic acid; paraquat; peroxisome proliferator activated receptor γ; pulmonary fibrosis; transforming growth factor‑β/Smad3.