Protective effects of ulinastatin and methylprednisolone against radiation-induced lung injury in mice

Abstract

The effectiveness of ulinastatin and methylprednisolone in treating pathological changes in mice with radiation-induced lung injury (RILI) was evaluated. Forty C57BL/6 female mice received whole-chest radiation (1.5 Gy/min for 12 min) and were randomly allocated into Group R (single radiation, n = 10), Group U (ulinastatin treatment, n = 10), Group M (methylprednisolone treatment, n = 10), or Group UM (ulinastatin and methylprednisolone treatment, n = 10). Another 10 untreated mice served as controls (Group C). Pathological changes in lung tissue, pulmonary interstitial area density (PIAD) and expression levels of transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in lung tissue, serum and bronchoalveolar lavage fluid were determined. Alleviation of pathological changes in lung tissue was observed in Groups U, M and UM. Treatment with ulinastatin, methylprednisolone or both effectively delayed the development of fibrosis at 12 weeks after radiation. Ulinastatin, methylprednisolone or both could alleviate the radiation-induced increase in the PIAD (P < 0.05 or P < 0.01). Treatment with ulinastatin, methylprednisolone or both significantly reduced the expression of TNF-α, but not TGF-β1, at 9 weeks after radiation compared with Group R (P < 0.01). Ulinastatin and/or methylprednisolone effectively decreased the level of TNF-α in lung tissue after RILI and inhibited both the inflammatory response and the development of fibrosis.

Radiation-Induced Lung Injury (RILI)

“…Targeting inflammation represents an alternative approach to reduce adverse effects during radiotherapy. In 18 Gy irradiated C57Bl/6 mice, intraperitoneal injection of methyl prednisone, an immune suppressor (40 mg/kg a day), for 7 days reduces TGF-β1 and TNF-α in lung tissue at 9 weeks after radiation exposure delaying the development of fibrosis at 12 weeks after irradiation (166). Statins (HMG-co-reductase inhibitors) ameliorate endothelial function by increasing the concentration of endothelial nitric oxide synthase (eNOS), which promotes anti-inflammatory signaling, prevents apoptosis, increases vasodilatation, and reduces platelet adhesion (157).…”

Nicaraven Exerts a Limited Effect on Radiation-Induced Inhibition of Tumor Growth in a Subcutaneous Murine Tumor Model

“…To obtain better outcomes of radiotherapy, it is still asked to reduce the early and late side effects, as well as to increase tumor response (19,20). Multiple approaches, such as the use of radio-protectors (pre-radiotherapy) or radio-mitigators (during or immediately post-radiotherapy) have been tested clinically to reduce the side effects of radiotherapy (21)(22)(23)(24)(25)(26)(27)(28)(29). However, there is still no clear evidence of how the approaches affect the sensitivity of cancer cells to radiation.…”

Annexin A1‑mediated inhibition of inflammatory cytokines may facilitate the resolution of inflammation in acute radiation‑induced lung injury

“…Various strategies and drugs have been applied for the prevention and treatment of RILI, with poor therapeutic effect (3)(4)(5)(6). Glucocorticoids have been administrated in numerous clinical studies for the treatment of acute RILI (1,(7)(8)(9). However, prolonged usage of high doses of glucocorticoids can lead to a number of side effects, including osteoporosis, abnormal glucose metabolism, digestive tract ulcers and infection (10).…”