Using bosentan to treat paraquat poisoning-induced acute lung injury in rats

Abstract

Background: Paraquat poisoning is well known for causing multiple organ function failure (MODS) and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning.

Objective: To study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat.

Method: A total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning); the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day); and a control group (rats were administered intragastric physiological saline). On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1), endothelin-1 (ET-1), and hydroxyproline (HYP) in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes.

Result: The TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered.

Conclusion: Bosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.

Figure 1. HE stain of control group (×200).

Lung tissue is normal. The alveolar space has a normal interstitium structure and no effusion.

Figure 2. Masson stain of control group (×200).

Lung tissue is normal. The alveolar space has a normal interstitium structure, and no effusion.

Figure 3. HE stain of PQ group (×200).

The inflammatory process with marked infiltration of leukocytes into interstitial and alveolar spaces, edema, alveolar distortion, and thickening of the alveolar wall.

Figure 4. Masson stain of PQ group (×200).

The alveolar wall was significantly thickened, there was evidence of phoroblast hyperplasia and fibroglia fibrils, which were obviously hyperplastic.

Figure 5. HE stain of bosentan group (×200).

The damage is improved more than that of the PQ group, and less inflammatory cell infiltration were found in the interstitial lung and alveoli, interstitial edema and alveolar hemorrhage were ameliorated.

Figure 6. Masson stain of bosentan group (×200).

The damage is improved relative to the PQ group. Alveolus interstitium was thinner and few phoroblast was observed.

Figure 7. The Type II alveolar epithelial cells of the control group (×8000).

The Type II alveolar epithelial cells have a normal structure.

Figure 8. The Type II alveolar epithelial cells from the PQ group (×8000).

The nuclei were collapsed and contained dense heterochromatin; the endoplasmic reticulum tended to be vesiculated, the basement membranes were absent or disrupted, the mitochondria was vacuolated and the number of lamellar bodies clearly decreased.

Figure 9. The Type II alveolar epithelial cells in the bosentan group (×8000).

The damage was ameliorated to some degree relative to the PQ group. Their nuclei membrane and the endoplasmic reticulum were integral and smooth, the mitochondrial cristae were limpid but still a litter disorder, vacuolation of the lamellar bodies were ameliorated, a few mature lamellar bodies were observed.