FIGURE 3.

Modified extended bleomycin (BLM) model with revised dosing schedule. a) Model illustration. Male Sprague-Dawley rats were treated with BLM 12 times at 3 mg·kg⁻¹ (Day 0, 14, 28, 42, 56, 70) and 1 mg·kg⁻¹ (Day 1 to day 6) (0.5 mL·kg⁻¹) to induce chronic lung damage. ND-L02-s0201 was dosed i.v. weekly or once every two weeks for 10 weeks starting from day 18. b–d) Animals were subjected to weekly ND-L02-s0201 treatment, two cycles of 5-week treatments: one initial dose of 2 mg·kg⁻¹ plus four follow up doses of 0.5–2 mg·kg⁻¹. 2 × 5: 2 mg·kg⁻¹ for 5 weeks; 2 + 1.5 × 4: 2  mg·kg⁻¹ initial then 1.5 mg·kg⁻¹ for 4 weeks; 2 + 1 × 4: 2 mg·kg⁻¹ initial then 1 mg·kg⁻¹ for 4 weeks; 2 + 0.5 × 4: 2 mg·kg⁻¹ initial then 0.5 mg·kg⁻¹ for 4 weeks. e–g) Animals were subjected to ND-L02-s0201 treatments, either weekly at doses of 0.3–3 mg·kg⁻¹ for 10 doses or once every two weeks at doses of 2 and 3 mg·kg⁻¹ for five doses. Lung hydroxyproline (HP) content (b and e), trichrome score (c and f), and histology score (d and g) were performed as described in figure 1 following necropsy on Day 84. Statistically significant difference was based on comparing to corresponding vehicle group. *: p<0.05; **: p<0.01; ***: p<0.001.