Beneficial effects of early (but not late) intervention of heme oxygenase-1 on bleomycin-induced pulmonary fibrosis in mice.

The aim of this study is to explore the effects of early and late intervention in heme oxygenase-1 (HO-1) expression or activity on pulmonary fibrosis in mice. Mice were divided into four groups: one control and three bleomycin hydrochloride-induced groups in which mice were administered phosphate-buffered saline (PBS), hemin or Cr (III) mesoporphyrin IX chloride (CrMP). Early intervention with hemin, an HO-1 inducer, abrogated bleomycin-induced pulmonary fibrosis (fibrotic/reparative score decrease from 21.0±2.4 to 13.8±1.7, P<0.01), and early intervention with CrMP, an HO-1 inhibitor, worsened bleomycin-induced pulmonary fibrosis (fibrotic/reparative score increase from 21.0±2.4 to 32.5±2.9, P<0.01). Elevated glutathione expression and reduced expression of TGF-β1, hydroxyproline, LDH and MDA were seen in the lungs of the early hemin intervention group compared to that seen in the PBS group (P<0.05). These results taken together show that HO-1 can prevent or ameliorate pulmonary fibrosis and oxidative stress and inflammation at an early stage of pulmonary fibrosis.